Materials Science and Engineering R 125 (2018) 1–41

Contents lists available at ScienceDirect

Materials Science and Engineering R

journal homepage: www.elsevier.com/locate/mser

Naturally-derived biopolymer nanocomposites: Interfacial design,

properties and emerging applications
Rui Xiong, Anise M. Grant, Ruilong Ma, Shuaidi Zhang, Vladimir V. Tsukruk*
School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0245, USA

ARTICLEINFO ABSTRACT

Article history:
Received 23 January 2018 Naturally derived materials with hierarchical organization are attractive candidates for high -
Accepted 26 January 2018 performance and functional bionanocomposites because of their renewability, biocompatibility,
biodegradability, flexibility, and the availability of multiple reac tive sites for introducing novel
Keywords: functionalities. Complementary to these inherent properties, the synergistic combination of biological
Bionanocomposites and synthetic components facilitated by strong interfacial interactions, can substantially enhance the
Natural polymers structural performance and facilitate added functionalities of these bio-enabled nanocomposites. In this
Nanocellulose review, we discuss the current progress of naturally-derived bionanocomposites that has advanced our
Silk fibroin understanding of the biological/synthetic interfaces. In these bionanocomposites, various novel synthetic
Mechanical performance
nanomaterials (e.g., graphene, carbon nanotube, mineral nanoparticles and metallic nanoparticles) are
Functional properties
efficiently integrated with biological components to achieve novel properties such as superior electrical
and thermal conductivity, controlled gas barrier properties, complex actuation, and unique optical
properties. Two popular biocomponents, nanocellulose and silk, are mainly discussed in this review as
representatives of classes of polysaccharides and polypeptides with some other biopolymers briefly
discussed as well. The structures and morphologies, processing strategies, tailored functionalities and
emerging applications of these bionanocomposites are analyzed and summarized. Finally, we present an
outlook on the current trends in providing structural and interfacial enhancement as well as emerging
applications which will employ new optical, sensing, structural, and actuating functionalities and
properties.
© 2018 Elsevier B.V. All rights reserved.

Contents

1. Introduction ........................................................................................................................................................................................................................... 2
2. Bionanocomposites and their properties ........................................................................................................................................................................... 3
2.1. Functional benefits ................................................................................................................................................................................................... 4
2.2. Structural enhancement ........................................................................................................................................................................................... 5
2.3. Environmental benefits ............................................................................................................................................................................................ 5
3. Synthetic components for bionanocomposites ................................................................................................................................................................. 5
3.1. Carbon nanomaterials .............................................................................................................................................................................................. 5
3.2. Mineral nanoparticles............................................................................................................................................................................................... 6
3.3. Metallic nanostructures ............................................................................................................................................................................................ 7
4. Processing of bionanocomposites ........................................................................................................................................................................................ 9
4.1. LbL assembly .......................................................................................................................................................................................................................... 9
4.2. One-pot directed assembly (vacuum assisted filtration and cast-drying) ........................................................................................................ 10
4.3. Fiber-spinning techniques ..................................................................................................................................................................................... 11
4.4. Freeze-drying .......................................................................................................................................................................................................... 11
4.5. Micropatterned bionanocomposites ..................................................................................................................................................................... 11

* Corresponding author.
E-mail address: vladimir@mse.gatech.edu (V.V. Tsukruk).

https://doi.org/10.1016/j.mser.2018.01.002
0927-796X/© 2018 Elsevier B.V. All rights reserved.
2 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

4.5.1. Masks based micropatterns ..................................................................................................................................................................... 12

4.5.2. Inkjet printing ........................................................................................................................................................................................... 12
4.5.3. 3D printing ................................................................................................................................................................................................ 12
4.6. Kirigami and origami structures ........................................................................................................................................................................... 13
5. Polysaccharides for bionanocomposites ............................................................................................................................................................................. 14
5.1. Nanocellulose components .................................................................................................................................................................................... 14
5.1.1. Preparation of nanocellulose .................................................................................................................................................................... 15
5.1.2. Different forms of nanocellulose materials ............................................................................................................................................. 15
5.2. Current and emerging applications of nanocellulose materials ........................................................................................................................ 16
5.2.1. Structural applications ............................................................................................................................................................................. 16
5.2.2. Optical applications .................................................................................................................................................................................. 18
5.2.3. Electronic biodevices ................................................................................................................................................................................ 21
5.3. Other polysaccharides: brief introduction ...........................................................................................................................................................22
5.3.1. Chitin and chitosan ..................................................................................................................................................................................22
5.3.2. Alginates .................................................................................................................................................................................................... 23
6. Proteins for bionanocomposites ........................................................................................................................................................................................23
6.1. Overview of silk: source and structure ................................................................................................................................................................... 23
6.2. Processing of silk: extract, chemical and non-chemical manipulation ............................................................................................................ 24
6.3. Applications of silk nanocomposites ...................................................................................................................................................................... 26
6.3.1. Biomedical applications ............................................................................................................................................................................ 26
6.3.2. Biodevices from silk materials ................................................................................................................................................................. 27
6.4. Other fibrous proteins for bionanocomposites ....................................................................................................................................................28
6.4.1. Collagen and gelatin ................................................................................................................................................................................28
6.4.2. Keratin components .................................................................................................................................................................................30
7. Polynucleotides for bionanocomposites ............................................................................................................................................................................. 30
7.1. Overview of polynucleotides .................................................................................................................................................................................. 30
7.2. Soft nanostructures: DNA origami ......................................................................................................................................................................... 30
7.3. Sensing applications of bionanocmposites ............................................................................................................................................................. 31
8. Carbonized bioderived materials ......................................................................................................................................................................................32
9. Conclusions, trends, and perspectives .............................................................................................................................................................................. 33
Acknowledgments ..............................................................................................................................................................................................................36
References ............................................................................................................................................................................................................................ 36

1. Introduction Nature is an outstanding resource—offering both innovative

designs and robust building components to construct the next
Prospective nanomaterials for enabling new nanotechnologies generation of functional bionanomaterials. For example, spiders
and emerging applications require added functionalities and extrude silk fibers with elastic moduli that rival the strongest
enhanced structural robustness. For instance, apparel should not commercial polymers and carbon fibers thanks to their hierarchi-
only protect against abrasive external forces, but also could provide cal organization of b-sheets and amorphous domains [9]. These
real-time monitoring of the health of the wearer and detect toxic silk webs are also highly adhesive, which has the auxiliary function
external agents [1]. Vehicles and aircrafts must be equipped to of capturing prey. On the other hand, abundant natural wood or
transport and protect occupants from external hits and endure bamboo materials possess an exceptionally high combination of
hours of ultraviolet radiation without exterior degradation [2–4]. toughness and strength rarely achieved in synthetic materials and
In general, advanced equipments in extreme environments, structures [10]. Understanding how the mechanisms and design
wearable biodevices at human-technology interfaces, real-time features in natural materials yield extraordinary properties can
monitoring devices, high-capacity energy storage devices and enable the development of high-performance bio-derived syn-
novel robust multifunctional bioimplants require next-generation thetic-biological nanocomposites with unique performance and
multifunctional composite nanomaterials. novel functionalities.
Advanced bio-derived nanocomposites with added function- Relevant biopolymers important for prospective bionanocom-
alities open a promising route toward generating the character- posites considered in this review can be divided into three classes
istics necessary to meet the current and future needs of modern by their monomeric unit composition: polysaccharides, protein/
technology development because they synergistically combine polypeptides and polynucleotides (Fig. 1). Among them, cellulose,
the strength and functionality of constituent materials to yield chitin/chitosan and alginate are three common polysaccharides
novel nanomaterials with enhanced utilities such as exceptional bonded by glyosidic linkages; while silk, collagen and keratin are
mechanical, electrical and optical properties along with potential three typical proteins consisting of long chains of amino acid
sustainability, biocompatibility, environmentally-friendly proc- residues. These biopolymers are renewable and can be derived
essing, and low toxicity. This array of unique and often orthogonal from natural sources such as plants, exoskeletons of arthropods,
properties offers opportunities to create robust functional devices skin, silkworm cocoon, spider webbing, and hair [11–15]. Finally,
that are not only strong, flexible, stretchable, and compressible, deoxyribonucleic acid (DNA) is a polynucleotide that carries
but also multifunctional, with added properties in chemical genetic information to instruct the growth, function and repro-
sensing, actuation, and smart-shielding of gas, moisture and duction of living organisms and many viruses.
radiation [5–8]. The enhanced biocompatibility of these nano- Due to multi-level systems of intramolecular and intermolecu-
materials make them ideal candidates for various demanding lar weak interactions combined with complex multi-domain
human-technology interface and biomedical applications, rang- secondary structure, biopolymer components generally self-
ing from wearable biosensors to functional implants and body assemble into various highly organized hierarchical forms, such
protection. as nanobeads [16], helical nanofibers [17] and flexible nanosheets
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
Fig. 1. The molecular structures and sources of naturally derived biopolymer components for bionanocomposites.
[18]. Biopolymer matrices add structural strength and new
functionalities, especially if combined with complementary
nanoscale synthetic components with proper dimensions and
functionalities. Although some progress on various fabrication
strategies for combining biological and synthetic nanocomponents
has been achieved in the past decades, the mechanical and
functional performance of the corresponding bionanocomposites
remain far below theoretical predictions due to poor understand-
ing of principles and mechanisms of intimate interactions,
processing, and organization.
In this review, we summarize recent progress in the synthesis,
design, and fabrication of select naturally derived bionanocompo-
sites for emerging applications. Particularly, we focus our
discussion on the interfacial interactions between synthetic and
biological components, comparing different routes of component
assembly, and analyzing the structural and functional properties of
individual components and corresponding nanocomposites. To
facilitate discussion, we specifically select two most representative
popular biopolymers from polysaccharides and proteins respec-
tively, nanocellulose and silk fibroin, for detailed analysis of state of
the art in their use for bionanocomposites. We focus on their
outstanding mechanical robustness, anisotropic and amphiphilic
character, rich interfacial interactions with synthetic components,
and sustainability. Their availability also makes them interesting
for modern large-scale applications. Most importantly, near-
ambient and universal fabrication strategies, common interfacial
design and extended applications reported for nanocellulose and
silk are also applicable for other polysaccharides and proteins
because of their fundamentally similar chemical structures and
interactions. Finally, the focus of this review will be on how their
interactions and organization with synthetic nanoscale
3
components enable advanced applications and offer a perspective
on the challenges that should be considered for practical
applications.
For the sake of balance, some other important biocomponents
such as polynucleotides will be briefly discussed as well, though
their prospective applications are quite different and somewhat
limited now and overall prospective for bionanocomposites is only
emerging. Even if DNA/RNA-based assembly is drawing increasing
attention because of incredibly precise control over the nano-
structure, e.g. 3D DNA origami, we only briefly discuss polynucle-
otide-based assembly in this review and direct more interested
readers to many recent reviews on DNA [19–24].
2. Bionanocomposites and their properties
Bionanocomposites possess many inborn advantages, such as
renewable, biocompatible, biodegradable, mechanical-robust, and
multifunctional features, over synthetic polymers based materials
because of the presence of biopolymers. Synthetic components can
be incorporated into the biopolymer matrix with controlled
dispersion and highly ordered organization depending on the
desired applications, for instance, in bioelectronics and drug
delivery [25,26], health and environment monitoring [27,28],
energy generation and storage [29], and lightweight structural
support (Fig. 2) [30].
Specifically, to realize high electrical conductivity, conductive
components such as carbon nanostructures and metallic nano-
particles can be introduced into the biopolymer matrix. The high
stretchability can be achieved via structural design and introduc-
tion of elastomeric elements and toughening components. Below,
we introduce the interesting properties of bionanocomposites in
4 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

Fig. 2. Materials design and fabrication of biopolymer nanocomposites for diverse structural and functional applications: (a) bioactive gyroid scaffolds for tissue engineering,
reproduced from [26] with permission. Copyright 2015 John Wiley & Sons. (b) bionanocomposite sensors, reproduced from [27] with permission. Copyright 2017 John Wiley &
Sons. (c) cellulose-based microwave devices [29] with permission. Copyright 2015 Jung et al. licensed under CC BY 4.0. (d) bioinspired silk fibers, reproduced from [30] with
permission. Copyright 2017 Ling et al. licensed under CC BY 4.0.

terms of functionalities, structural benefits and overall impact
(Fig. 2).
2.1. Functional benefits
Bionanocomposites can be conductive, optically active, and
biodegradable as well as exhibit reduced cytotoxicity and
enhanced bio-compatibility due to the incorporation and organi-
zation of bio-derived components. The pre-programmed, con-
trolled design of functional biointerfaces between synthetic and
biological components is highly desired and involves many novel
morphologies such as core-shell structures [31–33]. These
structures not only retain the unique properties of incorporated
synthetic nanostructures (e.g., magnetic or optical properties) but
can also provide additional biofunctionality.
Among recent examples, a series of adaptive bionanocompo-
sites were reported to mimic natural plants and animals that adapt
to external environments by changing their shape or color [27,34–
39]. Another remarkable adaptive ability is self-healing [40]. This
ability enables organisms to regenerate complex structures such as
skin and bark after external damages. Inspired by this feature,
various bionanocomposites with excellent self-healing properties
were fabricated via dynamic metal ionic interaction and hydrogen
bonding design [19,34]. For instance, Cao et al. [27] fabricated a
highly sensitive and self-healing bionanocomposite by embedding
a conductive network of carbon nanotubes into a chitosan-
nanocellulose matrix. The corresponding nanostructured compo-
sites demonstrate fast, repeatable, and efficient self-healing that
benefited from hydrogen bonding between the chitosan and
nanocellulose components.
Bionanocomposites with responsive behavior are also widely
demonstrated, which can change mechanical properties, wetting
behavior, optical appearance, and shape in response to pH [35],
temperature [36], electricity [37], humidity [38] and light [39].
Inspired by plants that change shape in response to humidity
variation, Wang et al. [38] reported that nanocellulose films
possess reversible actuation behavior induced by swelling and
deswelling. The swelling/deswelling of nanocellulose films is
highly sensitive to environmental humidity and leads to reversible
actuation of films through bending. Some bionanocomposites
show dual functionalities such as conducting artificial muscles
used for actuator applications [41] or mechanically enhanced
nanocomposites with antimicrobial properties [42].
Another example is the fabrication of conductive bionanocom-
posites for flexible electronic devices. In this field, there has been
extensive research interest in the incorporation of highly conduc-
tive graphene materials into biopolymers to construct conductive
biocomposite materials [43–46]. These studies show that
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
biopolymer-graphene nanocomposites can be tuned to very high
electrical or ionic conductivity by selection of components,
composition, and organization [47].
2.2. Structural enhancement
Although all these primary biopolymers consist of flexible and
semi-flexible primary structures, the secondary and terciary
organization of the biopolymers, as induced by complementary
weak intra- and intermolecular bonding, folding, or coiling, are
needed to demonstrate enhanced mechanical and functional
performance for demanding applications. For example, silk II
polymorph confers high local strength thanks to intermolecular
hydrogen bond driven self-assembly of poly-(Gly-Ala) into b-sheet
nanocrystals [48]. These b-sheet nanocrystals are key structural
elements for making spider silk fibers with exceptional tensile
strength and extensibility when combined with covalently
interconnected, high compliance random silk I polymorph
domains.
In another example, nanocellulose, a common natural compo-
nent, is made up of several parallel packed molecular chains
stabilized by both hydrogen bonding and van der Waals’ forces into
nanofibrillar structures [49]. Their high degree of crystallinity (70–
80%) facilitates extremely high elastic moduli of 150–220 GPa [50].
These strong nanofibrils in the form of nanocrystals or nanofibers
act as high performance reinforcing 1D components due to their
high aspect ratio and high stiffness. For example, nanocellulose is
widely used to reinforce a wide selection of materials, including
synthetic polymers [51], carbon matrices [52], and inorganic
nanoplates [53], increasing elastic modulus by an order of
magnitude [54,55].
On the other hand, bio-derived polymers can transform the
assembly of synthetic components into nanocomposites with
superior mechanical properties. For instance, graphene papers
have a comparatively low elastic modulus of 40 GPa and strength of
300 MPa due to weak interfacial interactions within their
laminated microstructure [56]. This stands in sharp contrast to
the high elastic modulus (1 TPa) and strength (130 GPa) of
individual monolayer graphene structures [57]. By adding very
small weight fractions of biopolymers such as silk and chitosan,
these graphene papers can be converted into stronger and tougher
nanocomposites as demonstrated in several recent reports [58–
60].
2.3. Environmental benefits
At the end-of-life, discarded bionanocomposites can be readily
degraded into their constituent organic building blocks. Therefore,
the prospective renewable, biodegradable, and green processing
characteristics of biopolymeric materials can significantly reduce
the carbon dioxide emissions and hazardous waste. To realize or
enhance these green benefits, various functional nanocomponents,
which possess strong and complementary interactions with
biopolymers, must be incorporated into the biopolymer matrix
to obtain desired mechanical enhancement or added functionali-
ties.
In the following section, we discuss the role of different
nanocomponents in the structural and functional benefits through
various non-covalent interactions or covalent binding.
3. Synthetic components for bionanocomposites
To introduce new functionalities, active synthetic nanoscale
components in the form of 0D nanoparticles, 1D nanofibers/
nanorods/nanotubes, or 2D nanoplates/nanosheets can be incor-
porated into the biopolymer matrix. A wide variety of
5
combinations of bio-derived and synthetic components can bring
added functionality such as electrical and thermal conductivity,
optical activity, light emission, magnetic properties and catalytic
activity. However, it is worth mentioning that the most critical
challenge for the processing of nanocomponents is their uncon-
trolled aggregation, which can result in the modest improvement
or even deterioration of mechanical performance.
In contrast to common synthetic nanomaterials with usually
limited functional sites, biocomponents considered here possess a
rich variety of functional groups capable of multi-scale hydrogen
bonding, Coulombic interactions, hydrophobic-hydrophobic inter-
actions, van der Waals interactions, p-p interactions, and covalent
bonding with a variety of external components. This broad
spectrum of weak interactions brings benefits and challenges for
novel bionanocomposites. In fact, these interactions are enable
high-efficient transfer of loads across component interfaces for
enhanced mechanical performance, but also make processing
difficult due to large-scale and non-uniform aggregation of
nanocomponents during processing. These localized aggregates
and related defects accelerate catastrophic failure in nanocompo-
site materials under practical conditions.
In this section, we will discuss the most popular synthetic
nanocomponents and their interfacial interactions with select
biopolymers, which are currently exploited for the fabrication of
novel bionanocomposites, including carbon nanomaterials, min-
eral nanoparticles, and metallic nanostructures.
3.1. Carbon nanomaterials
Widely exploited carbon nanomaterials in consideration here
include graphene, one of the strongest flexible components;
nanodiamonds, one of the hardest naturally occurring materials;
and active amorphous carbon particles, one of the most porous
materials. Among them, 1D and 2D flexible carbon monolayer-
based nanomaterials (carbon nanotubes (CNT), graphenes and
graphene oxides (GO)) with graphitic structure attract the most
attention because of their excellent mechanical properties,
electrical and thermal conductivity, and large specific surface
area [61–64].
The integration of carbon nanocomponents within biopolymer
matrices provides the bionanocomposites with impressive me-
chanical reinforcement and functional properties, including
controlled electrical conductivity, thermal conductivity, gas barrier
properties, sensing abilities, and controlled molecular porosity
[65–71]. Even at low loading, the mechanical performance and
functionalities of biopolymer matrices can be significantly
improved. For example, Mezzenga et al. reported a record-low
electrical percolation threshold of 3.3 ×10—2 vol% for GO-gelatin
nanocomposites, benefiting from the homogeneous dispersion of
GO nanosheets within the gelatin matrix [72]. Kabiri et al. reported
that adding only 0.8 wt% of GO nanosheets into the cellulose
nanocrystal (CNC) acetate can increase tensile strength by 60%,
reaching 160 MPa, and facilitate improved vapor barrier properties
[73]. Interestingly, Wang et al. reported that silk fibers, which are
loaded with traces of CNT and graphene components by directly
feeding Bombyx mori larval silkworms with CNT and graphene
solutions, demonstrated remarkable mechanical enhancement
[74]. Further pyrolyzation of these nanocarbon-loaded silk fibers
resulted in carbonized nanocomposites with greatly enhanced
electrical conductivity.
Until now, the preparation of 2D graphenes included the
mechanical exfoliation of graphite by ‘scotch tape’ [75], electro-
chemical exfoliation [76], mechanical exfoliation by strong
shearing force [77], and growth by chemical vapor deposition
(CVD) [78]. Although the CVD method has the capability of
producing large-scale and near single crystal graphene, CVD
6 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
requires high temperature, high vacuum, expensive substrates and
precisely controlled experimental parameters, resulting in high
cost and problematic scalability. Beyond large uniform graphene
sheets, Dai’s group reported the production of uniform graphene
nanoribbons by unzipping highly crystalline CNTs [79]. Finally,
CNTs were prepared by CVD growth, which can control the
orientation of CNTs for obtaining the strongest CNT-based
materials.
Tuning the surface chemistry of carbon nanomaterials affords
control over interfacial interactions with biopolymer matrices
(Fig. 3). The hydrophobic-hydrophobic interactions between
proteins with graphene and CNT components are commonly
explored for improved performance.
Some combinations of carbon materials with proteins also
count on p-p interactions because of the presence of the tyrosine
units. For instance, Pattammattel et al. reported a highly efficient
aqueous method to exfoliate graphite into a high quality graphene
dispersion in the presence of bovine serum albumin (BSA) proteins
[80]. In this approach, defect-free graphene of 0.5 mm size with 3–
5 layers can be exfoliated layer-bylayer via the strong shear force
and strong hydrophobic-hydrophobic/p-p interactions between
BSA and graphene surfaces. These graphene bio-dispersions
demonstrated good aqueous stability in wide ranges of pH and
temperature, and solid films from these mixtures demonstrate
high electrical conductivity of 32,000 S/m.
In another example, Li et al. [81] reported a novel CNT/protein
core-shell nanostructure fabricated via sonication of CNTs and b-
lactoglobulin protein that has a compact globular structure with a
hydrophobic core. The sonication would expose the inner
hydrophobic domains of the protein to the hydrophobic CNTs for
the formation of stable CNT dispersions by hydrophobic-hydro-
phobic interactions. Additionally, the hydrophobic-hydrophobic
interactions of CNT and protein components can be further
promoted by the partial denaturation of protein, resulting in higher
content of hydrophobic domains. Similarly, the main interactions
between polysaccharides and carbon nanomaterials are the
hydrophobic-hydrophobic interactions. For example, nanocellu-
lose was reported to be an ideal dispersing agent for graphene and
CNT components [82,83]. These dispersions can be fabricated into
Fig. 3. The enabling interactions between carbon nanomaterials and biopolymers.
various forms such as flexible and transparent papers, strong and
conductive fibers, and porous aerogels [84].
GO is a graphene derivative widely used as a precursor for
graphene due to its good dispersibility and processability in
aqueous environments [62,85]. It is usually produced from
graphite flakes by the thermal oxidation method as first suggested
by Hummers [86] and modified by successors [87]. The resulting
single monolayer carbon materials with high aspect ratio form
flexible sheets that possess a high density of epoxy and hydroxyl
groups on both sides of the lateral plane and carboxyl groups
around plane edges (Fig. 3). Notably, these functional groups can
also be partially removed by well-established GO reduction via
hydrazine [88], hydroiodic acid [89], high-temperature [90], or
microwaves [91] to produce highly conductive materials. Com-
pared with graphene and CNT components, GO is easier to
integrate with biopolymers because GO contains abundant polar
functionalities, which are capable of hydrogen bonding, polar-
polar, ionic, and covalent interactions with biopolymers.
Additionally, the co-existence of hydrophobic graphitic regions
and hydrophilic oxidized regions make a heterogeneous amphi-
philic surface [92,93]. This interesting property has two important
consequences: (1) GO sheets can strongly bond with either
hydrophobic or hydrophilic biopolymers and (2) the strength of the
interfaces can be further improved if a matching biopolymer
matrix is chosen. For example, the interfacial strength of GO sheets
and positively charged biopolymers such as chitosan can be
enhanced through a combination of hydrogen bonding, Coulombic
interactions and covalent bonding. The combination of GO and
amphiphilic biopolymers is also stabilized via hydrogen bonding
and hydrophobic interactions of organized micellar structures. For
instance, Wan et al. demonstrated that the strong interfacial
strength between GO and chitosan would result in manifold
enhancement for the tensile strength and toughness of GO films
[60].
3.2. Mineral nanoparticles
Combinations of biopolymers and mineral components are very
common in designing nanocomposite materials inspired by
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
natural mineral-based liketeeth [94], bones [95], and the dactyl
clubs [96]. Mineral nanoparticles of different shapes, such as 0D
nanoparticles, 1D nanowhiskers and 2D nanoplatelets, have
proven for easy fabrication of excellent reinforcing structures.
Among those, stiff nanoplatelets with thickness of 1 nm have been
most intensively studied due to their high aspect ratio, exceptional
reinforcement, high optical transparency, tunable gas barrier
properties, and good aqueous dispersibility. The elastic modulus of
these nanoplates has been estimated to be close to 270 GPa [97],
comparable to GO nanosheets. Additionally, the high aspect ratio,
2D shape allows them to assemble into highly organized, layered
morphologies to mimic natural structures such as nacre, which is
composed of aligned platelet-shaped aragonite (CaCO3 crystals)
adhered together by ultrathin chitin-protein biopolymer inter-
layers. Such well-ordered “brick-and-mortar” multilayered orga-
nization is critically important for achieving enhanced strength
and toughness, where the hard aragonite provides strength and
soft biopolymer layers dissipate deformation energy.
To mimic these natural structures, various mineral platelets,
including montmorillonite (MTM), CaCO3, hydroxylapatite, and
boron nitride, have been employed as hard building blocks adhered
together by various biopolymer interlayers [97–99]. To date,
numerous biopolymers from polysaccharides and proteins such as
cellulose [53], semicellulose [100], chitosan [101], alginate [102],
silk [103,104], and amyloid fibers [98] have been reported to
function as a glue, or “mortar”, component. The rich functional
groups of these biopolymers facilitate multiple hydrogen bonds
and hydrophobic-hydrophobic pairings with mineral nanoplates.
Additionally, electrostatic and covalent bonding can be used to
chemically modify these mineral particles to further enhance the
interfacial strength. For example, Yao et al. [105] loaded dopamine
on the cellulose nanofiber surface to strengthen interactions with
MTM platelets, especially at high moisture conditions when
Fig. 4. (a) Preparation of dopamine-conjugated CNFs and subsequent assembly of CNFs with MTMs as layered nanocomposites; (b) the SEM image of layered structure; (c)
Stress-strain curves of as-prepared film in water, reproduced from [105] with permission. Copyright 2017 American Chemical Society.
7
adhesion weakens (Fig. 4). The synergistic interactions of catechol/
metal ion chelation, hydrogen bonding, and hydrophobic-hydro-
phobic interactions at the interface of MTM platelets and cellulose
nanofibers lead to strong mechanical performance under chal-
lenging humidity conditions. Even swollen in water, these
bionanocomposites still exhibited high tensile strength and
modulus up to 57 MPa and 1.1 GPa, respectively.
It is worth noting that in addition to the direct mixing of mineral
with bioplolymer matrices another promising approach to
integrate mineral with biopolymers has emerged: the in-situ
growth of mineral which mimic the processing strategy of these
natural structural materials via biomineralization [106]. To date,
various mineral including CaCO3 and calcium phosphate were
grown within the biopolymer matrix. These biopolymer, especially
protein, can act as the template to regulate the growth direction
and shapes of these mineral. For example, Cheng et al. reported
that silk demonstrated a significant effect on morphology and
crystallographic polymorphs of CaCO3 crystals [107]. By control-
ling experimental conditions such as the temperature, pH value,
concentration, and molecular weight distribution of silk, a novel
hollow, rice-grain-shaped protein/mineral hybrid can be obtained
[107]. Liu et al. also demonstrated that silk component can control
the synthesis of stable and monodisperse CaCO 3 spheres [108].
Overall, these phenomena are important for developing new
biomaterials for advanced biomedical applications ranging from
drug delivery to bone tissue engineering [108–111].
3.3. Metallic nanostructures
The addition of metallic nanoparticles into the biopolymer
matrix adds functionalities beyond just common mechanical
reinforcement. In terms of functionalities, metallic nanoparticles
can provide the biopolymers with added electrical conductivity
8 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

[112], catalytic activity [113], and plasmonic properties [114].
However, ensuring the fine distribution of metallic nanoparticles
in a biopolymer matrix is a big challenge. To address this issue,
various ligands have been explored to modify nanoparticle
surfaces in order to provide more binding sites for biopolymers
and prevent nanoparticle aggregation [115–118]. Polyvinylpyrro-
lidone (PVP) is the most common ligand for the growth and
stabilization of nanoparticles in an aqueous environment and
during processing [119]. It aids in fine nanoparticle dispersion by
facilitating strong hydrogen bonding to the surrounding matrix.
Recently, Pan et al. [120] reported strong bionanocomposite films
produced by spray-induced assembly of silver nanowires and
thiolated chitosan. The strong interfacial interaction between
silver and chitosan, reinforced by Ag— —S covalent bonds, formed
robust films with strength of 250 MPa and Young’s modulus of
32 GPa.
Metallic nanoparticles can also be uniformly introduced into
the biopolymer matrix via in situ growth due to the utilization of
select biopolymers that are simultaneously good metal ion
reductants and stabilizers [112,121,122]. To date, various proteins
[112], DNA [123], chitosan [124] and nanocellulose materials [113]
have been used as biotemplates and efficient reductants for the
fabrication of multifunctional bionanocomposites with enclosed
nanoparticles in the applications of catalysis [113], sensor [114],
photothermal therapy [125] and antibacterial agents [126].
Additionally, metal oxide nanoparticles sometimes can be
substituted for metal nanoparticles because of their greater
aqueous processability and dispersibility within biopolymer
matrices [127,128].
In terms of manipulating the structural assembly of metallic
nanoparticles, an intriguing example is DNA origami, which relies
on manipulating the self-assembly characteristic of DNA base pairs
which can be used as templates for formation of complex metallic
nanostructures and organized nanoparticle arrays (Fig. 5) [129].
Weak, noncovalent interactions drive biomolecule supramolecular
assembly into helices, crystals, and fibers. Exploiting polynucleo-
tide propensity for assembly, scientists has produced cylinders and
helical constructs, demonstrating great potential for use as

Fig. 5. DNA-nanoparticle composites. a) DNA-nanoparticle assembly embedded in silica, reproduced from [141] with permission. Copyright 2012 John Wiley & Sons. b) Single-
crystal superlattice polyhedral matching Wulff construction predictions, reproduced from [142] with permission. Copyright 2013 Springer Nature.

Fig. 6. (a) The LbL assembly by dipping, spin and spray coating; reproduced from [150] with permission. Copyright 2015 American Association for the Advancement of
Science; (b) the AFM and scheme of LbL CNC microcapsules; reproduced from [151] with permission. Copyright 2015 American Chemical Society; (C) the layered structure of
LbL assembled silk and graphene oxide nanomembranes, reproduced from [156] with permission. Copyright 2013 John Wiley & Sons.
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
scaffolds for nanoparticle assembly. Through the chemical or
physical linking of DNA to cargo, nanocomposite bio-metallic
structures can be formed whereby DNA templates can guide,
reduce, and position metal ions or metallic cluster. A wide variety
of cargo materials have been directed by polynucleotides including
small molecules [130–132], metal nanoparticles [133–135],
vesicles [136], quantum dots [137], and simultaneous loading
with multiplexed cargo has been demonstrated [133].
Metal nanoparticles can be integrated into DNA strands to
enhance composite rigidity, and to serve as a template around
which DNA is organized [21]. DNA-nanoparticle assemblies have
shown increased geometric complexity with extension to long-
range ordered local organization [138,139], eventually leading to
controlled superlattice architectures with different symmetries
(Fig. 5). These complex architectures are controlled by DNA-linker
mix to create nanoparticle short-range order [140] or nanoparticle
geometry. Surrounding biological matrix can assist in building
embedded nanoparticle superlattices [141] and controlling ther-
mal annealing can lead to single-crystal nanoparticle lattice
formation [142].
4. Processing of bionanocomposites
Unlike synthetic thermoplastics that can be melt-extruded into
properly shaped bulk material parts, biopolymers are prepared via
solution processing because their thermal degradation temper-
atures are close to or lower than their glass-transition temperature
(Tg) [143]. In the past decade, solution assembly techniques were
developed to shape biopolymeric materials into various macro-
scopic forms, including membranes, microcapsules, fibers, aero-
gels, patterned microstructures, and stretchable structures. These
fabrication approaches are highly dependent on the physicochem-
ical properties of the biomaterials solutions, such as interactions
between building blocks, concentration, and viscosity. To date, the
Fig. 7. (a) Vacuum assisted filtration approach for preparing silk/graphene oxide films, reproduced from [157] with permission. Copyright 2015 American Chemical Society;
(b) the illustration of cast-drying technique for preparing PVA/CNF/MTM films, reproduced from [159] with permission. Copyright 2014 American Chemical Society.
9
most popular wet-chemistry approaches include layer-by-layer
(LbL) assembly, one-pot assembly approaches such as vacuum
assisted filtration and cast-drying, wet-spinning and electro-
spinning, freeze drying, and various micropatterning approaches
[52,144–147].
4.1. LbL assembly
LbL assembly is a popular strategy for preparing multilayered
thin membranes and coatings with pre-programmed composition,
controlled adhesion, gas barrier, and adaptable abilities [148]. This
technique allows the precise control of thickness, distribution, and
content of biocomponents at a single molecular layer level by
alternating deposition of the complementary components on
various substrates via tunable interfacial interactions such as
hydrogen bonding, electrostatic interactions and hydrophobic-
hydrophobic interactions [149,150].
The LbL technique also affords wide diversity in the selection of
substrate materials and specific deposition techniques (Fig. 6a).
Various bionanocomponents can be assembled on diverse sub-
strates such as flat wafers, glass, flexible films, fibers, particles, and
textiles via spin-coating, spray-coating, and immersive/dip-coat-
ing [150]. After LbL deposition, as-prepared layered bionanocom-
posite films with desired composition can be further annealed and
released from the substrate in a free-standing state by selective
dissolution of the sacrificial substrate or pull-off of the films for
further investigation, post-processing, or transfer for further
applications.
Recently, CNC microcages with a “haystack” shell morphology
were fabricated by assembling negatively charged CNCs on cationic
polyetherimide (PEI) modified surface of silica microspheres
(Fig. 6b) [151]. After the removal of the silica core, the resilient
cage-like microcapsules show an open nanofibrillated network of
CNCs with tunable large and open pores. It has been observed that
10 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
CNC microcapsules have large pore sizes up to 100 nm that allow
for the fast transport of large nanoparticles (30–100 nm). Notably,
the loading and unloading behavior of nanoparticles can also be
regulated by controlling the pH. Aside from CNCs, other related
biopolymers had been used to prepare the LbL microcapsules with
tunable porosity from single-component silks [152], modified silk
ionomers [153], and chitosan [154].
LbL assembly is also widely used for the fabrication of thin
organized bionanocomposite membranes with thicknesses as low
as a few nanometers [155]. To this end, Hu et al. [156] fabricated
novel freestanding robust bionanocomposites with thickness of
50 nm fabricated by spin-assisted LbL assembly from silk fibroin
and GO sheets (Fig. 6c). These silk-based nanomembranes show
remarkable mechanical strength with elastic modulus of 140 GPa
and strength of above 300 MPa due to their highly uniform
nanostructure achieved by the LbL technique and complementary
interfacial interactions. Moreover, Xie et al. demonstrate that LbL
assemblies of GO sheets and silk possess outstanding specific
penetration energy, significantly higher than that of Kevlar fabrics
and close to that of conventional multilayer graphene structures
[155].
4.2. One-pot directed assembly (vacuum assisted filtration and cast-
drying)
One-pot directed assembly overcomes major obstacles, such as
high cost and long fabrication time, for developing large scale and
Fig. 8. (a) Fiber spinning of CNC/PVOH composite fibers; (b) the stress-strain curves of CNC/PVOH fibers; (C) the SEM of CNC/PVOH fiber and the 2D WAXS data in inset,
reproduced from [168] with permission. Copyringht 2016 American Chemical Society.
thick laminated structures. It also gives an opportunity to obtain
well-defined and stratified films with precisely designed laminat-
ed morphology, structure, and composition at the nanoscale scale.
Bionanocomposites fabricated by these approaches afford a high
degree of materials compatibility, uniformity, and enhanced
physical properties [157,158], Compared to the traditional LbL
assembly, one-pot directed assembly is more efficient because it is
simpler, faster, and affords assembly of nanoscale-level dispersions
resulting in significantly improved nanocomposite properties and
relatively thick microscopic paper with large dimensions but lacks
precise control of local composition and morphology.
One-pot directed assembly can be classified into two specific
methods: vacuum assisted filtration and cast drying (Fig. 7). Both
methods require uniform premixing of the biopolymer solution
and nanofiller dispersion [157,159]. Subsequently, the colloidal
mixture in the vacuum assisted filtration case is passed through
commercial nanofilters with pores whose size is smaller than
nanofillers to allow the solvent to flow through while withholding
these nanofillers from aggregation with bound biopolymers as the
topmost layer.
In the cast-drying technique, the colloidal mixture is placed into
clean containers such as Petri dishes or deposited on a clean
substrates by various coating techniques such as bar coating and
spraying to obtain solid films after complete solvent removal. For
example, layered bionanocomposite films with layered morpholo-
gy can be readily fabricated by using biopolymer-GO mixture or
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
biopolymer-MTM co-dispersion via both vacuum assisted filtration
and cast drying [157,159,160].
4.3. Fiber-spinning techniques
Spinning techniques are conventional methods for fabrication
of bionanocomposite fibers, which can be categorized into two
types, wet spinning and electrospinning [161–163]. Wet spinning
has the advantage of large-scale production of biopolymer
microfibers and bundles of microfibers (Fig. 8).
In contrast, the electrospinning approach has the capability of
producing extremely fine nanofibers in the form of non-woven
mats which are ready for further processing [164–167]. Notably, 1D
nanostructures of reinforcing components can be aligned along the
fiber axis due to high-speed sheering forces during the spinning
process.
For example, Lee et al. [168] fabricated ultra-strong and stiff
CNC/poly(vinyl alcohol) (PVOH) nanocomposite fibers via wet
spinning gels of CNC and PVOH, followed by hot-drawing (Fig. 8). It
was observed that adding of CNC components not only provide the
direct reinforcement, but also increase the alignment and
crystallinity of PVOH. This synergistic effect resulted in remarkable
mechanical enhancement with strength and stiffness reaching
880 MPa and 30 GPa, respectively.
Recently, uniaxially aligned cellulose nanofibers reinforced by
CNCs were fabricated via electrospinning [169]. CNCs were finely
dispersed into the cellulose fiber matrix with preferred orientation
along the fiber axes. Such mutual orientation of components
resulted in significant enhancement of the mechanical perfor-
mance of cellulose nanofibers while improving their thermal
stability. Additionally, these nanofibers show potential for use as
scaffold materials for tissue engineering. Not only are they non-
cytotoxic, but they also exhibit a strong role in directing cellular
organization.
4.4. Freeze-drying
Freeze-drying, also known as lyophilization, is a dehydration
process that works by first freezing bionanocomposites in solution
or hydrogel [170]. Freeze-drying preserves the morphology of
nanocomposites in the wet state to prepare highly porous, ultra-
lightweight bionanocomposite aerogels. In this approach, the
Fig. 9. The fabrication of the synthetic nacre via ice template technique followed by mineralization, infiltration and hot-press; (b) the image of as-prepared synthetic nacre;
(c) the SEM image of cross-section of the synthetic nacre. Scale bar: 1 cm for b; 3 mm for c, reproduced from [178] with permission. Copyright 2016 American Association for
the Advancement of Science.
11
surrounding small molecular solvents are removed by sublimation,
avoiding the capillary force-induced collapse of the nanopores that
usually happen in conventional air drying. Freeze-drying is widely
adopted to prepare various bionanocomposite aerogels, including
those based upon cellulose [113], chitin [171], chitosan [172],
starch [173], alginate [174], and silk [175].
Notably, the macroscopic shape adopted by nanocomposite
aerogels is basically the same as the original solution container.
Thus, different product shapes can be obtained readily via
templating by a container shape. The microscopic morphology
of aerogels such as the pore size and distribution as well as shape
and orientation can also be controlled during the freeze-drying
process. The most well-known example is the ice-template
approach that can form nanostructures by regulating the growth
of ice crystal in the nanocomposites [176].
For example, Mao et al. [177] reported that a novel silk fibroin–
chitosan aerogel with controllable open-pore and oriented porous
structures can be constructed using the ice template technique.
This as-prepared aerogel showed predefined microfluidic channels
that could promote the mass transport, facilitating uniform cell
distribution and growth. Recently, Yu et al. demonstrated the use of
ice-template technique in the fabrication of the artificial nacre
(Fig. 9) [178]. In this study, they biomineralized aragonite platelet
within the uniform chitosan layered nanochannels that were
constructed by the ice-template. Then, silk molecules penetrated
the free space available within inner nanocomposite volume to
mimic the overall composition, morphology, and internal organi-
zation of natural nacre to achieve comparable or higher ultimate
strength and fracture toughness.
4.5. Micropatterned bionanocomposites
Micropatterned bionanocomposites with 2D or 3D organized
morphologies show interesting global physical properties and
peculiar localized distribution of components with mediating
stresses, deformations, foldability, and electrical conductivities.
Carefully designed micropatterns open a path to consider adaptive
behavior such as self-folding, self-rolling, and actuation. The
strategies that were developed to pattern bionanocomposites
mainly exploited well-known techniques such as mask based
patterning, inkjet printing, and 3D/4D printing.
12 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
4.5.1. Masks based micropatterns
Traditional mask based pattern techniques can be applied to
various solid surfaces by using a pre-patterned stamp pressed into
a softened polymer to emboss the pattern into the substrate
[179,180]. The stamp or mask must first be fabricated using
methods such as optical cutting, electron beam or focused ion
beam lithography, which enable parallel fabrication of predeter-
mined structures multiple times and at large areas. These
techniques are based upon soft lithographic techniques that have
been developed extensively in elastomeric materials in works
pioneered by Whitesides et al. [181,182] This original approach has
been extended by applying different types of microstamps,
sequential applications of microstamps, nanoimprinting
approaches, micromolding, and capillary transfer lithography
[183–185].
Developments in the patterning of silk- and nanocellulose-
based materials offer a good starting point in the patterning of
similar nanocomposites. For instance, Omenetto et al. demonstrate
that silk films could be employed in the transfer of micron-scale
patterned features similar to replica molding with PDMS stamps
[186]. Uncured silk-coated substrates have also been shown to be
able to pick up patterns via hot embossing at 100 ○C or water-
mediated nanoimprinting at room temperatures [187]. Parker et al.
generated patterned fibronectin into so-called nanofabrics by
depositing a fibronectin-containing slurry onto the surface of a
PDMS stamp with parallel 30-mm pitch channels [188]. These
structured assemblies of bio-derived components generally have
critical feature dimensions of tens to hundreds of microns
primarily limited by the resolution of mask used and spreading
of polymeric transfer agents [189]. Using specially designed
polymeric transfer agents and photolithography-generated master
masks have led to an increase in the theoretical resolution,
approaching tens of nanometers [190]. However, these innovations
in achieving high-resolution soft lithography patterning are
unlikely to be translatable to bio-derived polymers and their
nanocomposites due to the current mismatch in physical and
chemical properties between bio-sourced materials and state-of-
the-art soft lithography patterned transfer agents [189].
Fig. 10. (a) The shear-induced alignment of cellulose fibrils during direct ink writing and the anisotropic swelling effects of the as-prepared cellulose structure; (b) the
swelling behavior of flower-like cellulose structures. (scale bars, 5 mm, inset = 2.5 mm), reproduced from [207] with permission. Copyright 2016 Springer Nature.
In an example of recent developments of this approach to
bionanocomposites, an electrochemical microstamping technique
was exploited for fabrication of micropatterned GO/silk biopaper
with high electrical conductivity on select areas at ambient
conditions without damaging the silk matrix in order to prepare
highly conductive paper-like materials and corresponding sensors
[158]. In this research, selective electrochemical reduction
patterning with micron resolution was conducted with only
selected regions being electrically conductive. To obtain higher
resolution, well-defined 2D microstructures were prepared by
screen printing or by photolithography for masking the region of
reduction [191].
4.5.2. Inkjet printing
Inkjet printing is a direct printing technique for various liquid
“inks” with low-cost, high efficiency, good reproduction and easy-
operation. In this technique, a jet of a solution breaks up into
droplets, which are deposited onto a surface, and form a pattern
when the solvent evaporates [192]. The resolution of the final
pattern depends on the size of the droplets, the viscosity of the ink,
and the interaction between inks and substrates. Inkjet printing
has recently been extended to various biopolymer materials,
including silk [193], chitosan [194], and chitin nanocrystals [195].
These bio-inks can be printed onto target substrates with little or
no reduction of bioactivities to create DNA, protein and cell
patterns [196,197]. Versatility of ink-jet printers is facilitated by
choice of size of the nozzles (10–100 um). The choice of different
inks (solutions or dispersions) makes ink-jet printing a valuable
tool for constructing user-defined geometries of multilayer
structures with micron-scale precision and accuracy. In contrast
to the microcontact printing, the inkjet printing shows some
potential for the industrial-scale production due to its ability to
pattern across large print-scalable areas.
4.5.3. 3D printing
3D printing is an emerging powerful tool for the fabrication of
hierarchical 3D nanostructures by layer-by-layer printing of
dispersions and extrusion of melts. In the past decade, a growing
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
number of studies reported 3D printing of biomaterials for
biomedical applications such as tissue engineering and regenera-
tive medicine because it is efficient, low-cost, and has good
reproducibility [198]. Various polysaccharide and protein biopol-
ymers used as bio-inks to fabricate complex 3D microstructures
[199].
For example, a bio-ink consisting of peptide-modified biopol-
ymers and gellan gum were used to print brain-like 3D structures
that encapsulate discrete layers of primary neural cells [200]. Silk
based bioinks were also developed for high resolution 3D printing
of structures with adjustable mechanical properties for matching
soft tissue properties [201–203]. The supramolecular hydrogels
based on hyaluronic acid modified with either adamantine or
b-cyclodextrin were used to print 3D microstructures that are
capable of self-healing through the spontaneous restoration of
guest–host bonds between Ad and b-CD moieties [204].
Recently, so-named 4D printing approach has been introduced
by combining commercial 3D printing with responsive materials
for smart textiles, autonomous robotics and biomedical devices
[205]. These architectures can change their shape responding to
external conditions after printing initial planar structures [206].
For example, Lewis’ group [207] reported biomimetic 4D printing
of nanocellulose microstructures with well-defined features
inspired by the shape-morphing behaviors of plants in response
to external humidity. These printed architectures demonstrated
localized, anisotropic swelling behavior because of the alignment
of nanocellulose structures along prescribed printing pathways
(Fig. 10). After immersion into water, the programmable archi-
tectures automatically yield complex 3D structures as a result of
pre-programmed localized folding, with geometries resembling
that of plant petals.
Notably, these direct-writing techniques present an inevitable
drawback in terms of modest spatial pattern resolution and
relatively low throughput at large scale production. For instance,
the usual resolution of inkjet printing is at high micrometer-level
(~10–100 mm at best) because of the large drop size and clogging
problems for narrower nozzles, and fabrication time can easily
reach hours per s single structure. In contrast, the photolithogra-
phy and nanoimprinting techniques have the capability of
Fig. 11. (a) Micropatterns and mechanical performance of GO-PVA nanocomposites after kirigami photolithography, reproduced from [213] with permission, Copyright 2015
Springer Nature; (b) Structure and photographs of a slinky triboelectric nanogenerators by origami approach, reproduced from [215] with permission. Copyright 2015
American Chemical Society.
13
constructing patterns with nanometer-level resolution
(~100 nm) [181,208].
4.6. Kirigami and origami structures
Large volume top-down fabrication routines of functional
bionanocomposites have usually been confined to two dimensions,
whereas three-dimensional shapes enable more complex, hierar-
chical organization of molecules that is rarely achievable (e.g., see
examples of 3D printing above). The combination of the ease of 2D
fabrication with the functionality of 3D structures has rarely been
demonstrated to date. This interfacial stress emerges through the
combination of dissimilar materials, or through the transfer of
stresses along pre-defined points of contact. Whereas the
processing of bulk materials either through casting or extrusion
cannot generate micro- or meso-scale architecture by design,
methods for generating high resolution 3D structures such as 3D
printing or 3D photo-fabrication techniques are fundamentally
serial in nature, and cannot produce components fast and in
sufficient volumes beyond prototyping or customization applica-
tions. Thus, alternative strategies such as kirigami and origami,
have been introduced in order to involve or generate non-planar
materials. Existing kirigami strategies are largely based on
lithographic cutting then generating interfacial stresses to induce
self-folding in the material as was discussed above [209,210].
External stresses can be applied to the pre-programmed
materials to induce deformations to accommodate differential
interfacial stresses. The most well-known fabrication methods for
these purposes are origami and kirigami, traditional paper
handicraft techniques [211]. For instance, Rogers’ group used
lithography to generate kirigami cuts in an ultrathin silicon
structure in the shape of serpentine twists, pinned to an
elastomeric substrate at select anchor points. Compression of
the substrate causes the elevation of unanchored features off the
substrate into the z-dimension [212]. Overall, these methods
possess advantages in terms of precise nanostructure control, high
efficiency, large-scale production, generation of fibrous and porous
nanostructure as well as ultrahigh stretchability.
14 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
In another study, Kotov et al. [213] used top-down kirigami
patterning techniques to program nanocomposite paper (Fig. 11a),
whereby deformation induces folding of the 2D film in the z-
dimension while preventing unpredictable local failure and largely
increasing the paper strain from 4 to 370%. Notably, the kirigami
technique has the capability of realizing remarkable stretchability,
but this enhancement comes with a trade-off in overall strength. In
Kotov’s study, for example, the ultimate stress of this paper sharply
dropped from 200 MPa to 0.2 MPa after introducing a folding
pattern [213]. This diminished performance should be considered
before implementation of kirigami materials in practical applica-
tions and should be carefully considered for ultimate performance.
Origami, another known paper folding technique, which also
draws increasing research attention [214]. In contrast to destruc-
tive cutting techniques, origami integrally saves the intact
nanostructure of materials, enabling the excellent mechanical
performance of the final programed products. For instance,
inspired by the origami technique, Wang et al. [215] used paper
as the starting material to fabricate slinky- and doodlebug-shaped
triboelectric nanogenerators (Fig. 11b). These origami structures
are mechanically robust to stretch, lift, and twist in order to harvest
ambient mechanical energy from various kinds of human motions
in wearable materials option.
Overall, the choice of fabrication method is highly dependent
on the practical situation, including the interaction between
components, the functionality requirement, the mechanical
properties requirement, and the feasibility of different approaches
for different materials. For example, the fine dispersion of
nanofillers is a crucial factor for the fabrication of high-perfor-
mance nanocomposites. Therefore, the one-pot processing
approaches are not suitable for many cases, while LbL assembly
can be a very efficient approach for bionanocomposite fabrication.
5. Polysaccharides for bionanocomposites
Polysaccharides, the most abundant group of biopolymers by
weight, exist in various natural sources, including plants (cellulose
and xylan), sea-animal shells (chitin and chitosan) and algae
Fig. 12. The general routes for modification of nanocellulose, reproduced from [225] with permission. Copyright 2014 Isik et al. licensed under CC BY 3.0; the bottom inset
shows the molecular structure of nanocellulose, reproduced from [226] with permission. Copyright 2014 Springer Nature.
(alginate and carrageenan) [216,217]. As renewable biopolymers,
polysaccharides possess many favorable characteristics such as
low toxicity, biocompatibility, stability, low cost, and availability of
reactive sites for chemical modification [218]. In this section, we
mainly focus on nanocelluloses from the viewpoint of their
utilization for bionanocomposites [49]. We discuss the extraction
of nanocellulose, processing of various nanocellulose nanocom-
posites, and their applications in flexible devices.
5.1. Nanocellulose components
Nanocellulose components can be isolated from original
cellulosic sources by various methods, including acid hydrolysis
and mechanical treatment [49]. Additionally, nanocellulose
components can be produced by bacterial synthesis [219]. Nano-
cellulose not only inherits the intrinsic properties of cellulose
fibers, but also possess specific features of nanoscale materials
caused by its high aspect ratio (up to several hundreds) and high
surface area. The elementary component of nanocellulose in wood
is highly crystalline nanostructures with diameter of around 3 nm,
and consists of 5–6 molecular chains [49], providing individual
CNCs with elastic modulus as high as 150 GPa, comparable to
Kevlar fibers [220,221]. Moreover, nanocellulose possess a low
coefficient of thermal expansion of 0.1 ppm/K and high optical
transmittance (98% at 550 nm)—making these materials attractive
for flexible and transparent electronic devices [222].
The linear cellulose chains consist of repeat anhydroglucose
rings through b 1–4 glucoside linkages, which provide high
content of surface hydroxyl groups (Fig. 12) [223]. Various
chemical modifications of nanocellulose, such as esterification,
cationisation, carboxylation, silylation and polymer grafting have
been reported to date [224]. Most of the modifications explored
predominantly occur on the hydroxyl group of the sixth position,
which acts as a primary alcohol [225,226]. These modifications can
enhance the interfacial interactions between nanocellulose
components, improve dispersibility in different solvents and
matrices, and provide additional functionality. Fig. 12 gives a
schematic overview of the typical modifications in the
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 15

nanocellulose production route and the surface chemistry of the
final products [225,226].
5.1.1. Preparation of nanocellulose
Nanocellulose can be classified into three categories: CNCs,
cellulose nanofibers (CNFs) and bacterial nanocellulose (BNC)
[49,227]. The size, morphology and strength highly depend upon
the source and processing conditions. CNCs generally contain
highly crystallized nanostructures, while CNF and BNF types
consist of highly crystalline arrangements and perturbed location
referred to as amorphous regions, which can provide them more
flexibility and continuity.
Typically, CNCs are produced from the cellulosic fibers by acid
hydrolysis, where the more readily accessible amorphous regions
are cleaved to liberate rod-like crystalline cellulose sections [49].
When the appropriate hydrolysis level has been reached, the acidic
mixture is diluted, and the residual acids and impurities are
removed by repeated centrifugation and extensive dialysis. The
physical and chemical behavior of CNCs is strongly dependent on
the type of acid used during processing and its concentration, the
hydrolysis temperature and time, in addition to a cellulosic source.
Typically, these CNCs prepared from wood pulp have a diameter of
5–10 nm and length of 100–300 nm (Fig. 13a) [151].
CNF is normally produced from cellulosic materials by intensive
mechanical treatment, including high pressure homogenization,
grinding, and ultrasonic treatment [228,229]. To make the
preparation more efficient, Isogai et al. utilized 2,2,6,6-tetrame-
thylpiperidine-1-oxylradical (TEMPO) mediated oxidation to
introduce carboxylate groups into cellulosic materials for breaking
the strong hydrogen bonding of the cellulose nanofibers [230].
Using this method, individualized cellulose nanofibers with 3–
4 nm in diameter and a few microns in length can be produced
with conjugated straight segments of several hundred nm in
length (Fig. 13b). Excepting isolating from cell walls in plants,
nanocellulose can also be synthesized by several bacterial species
(e.g. Acetobacter G. xylinus) with low-molecular weight sugars or
other carbon sources [224]. The resulting BNC is in the form of a
pellicle that consists of a 3D cellulosic network structure with
randomly assembled ribbon shaped cellulose nanofibrils (Fig. 13c)
[49].
5.1.2. Different forms of nanocellulose materials
Nanocellulose can be processed and fabricated into various
forms with variable mechanical properties, including robust 1D
fibers, 2D optical transparent or iridescent paper, 3D soft and
highly compressible aerogels. The most common technique to
fabricate nanocellulose fibers is wet-spinning, which is widely
used by industry [231]. During the spin process, various kinds of
functional nanoparticles, such as magnetic nanoparticles and
electrical conductive nanoparticles can be added into the nano-
cellulose dispersions to produce multi-functional nanocellulose
fibers [232].
In contrast to the micron-scale size of wet-spun fiber, electro-
spinning generates nano-scale size cellulose fibers [169]. However,
to fabricate nanofibers that only consist of nanocellulose
components remains a challenge. Recently, ultra-strong cellulose
fibers with strength of 600 MPa and ultimate strain up to 12% were
prepared by a hydrodynamic alignment method [233]. These
cellulose fibers demonstrated highly ordered orientation that is
comparable to the strongest cellulose pulp fibers extracted from
wood (Fig. 13d). Hu’s group utilized a wet-drawing and wet-
twisting process to assemble BNC hydrogel into long BNC fibers
[227]. This technique not only retains the interconnected network,
but also allows the highly uniform alignment of nanofibers. These
as-prepared fibers show a good combination of high tensile
strength (826 MPa) and Young’s modulus (about 66 GPa).
Interestingly, CNCs is capable of self-assembling into a left-
handed chiral nematic liquid crystalline (LC) phase when the
dispersion concentration is above a critical value [234]. This
assembly is due to the CNC’s right-handed twist along the nanorod
axis [226]. Recently, the right-handed twist of individual CNCs
from different origins was observed by cryo-electron tomography

Fig. 13. AFM images of cellulose nanocrystals (a) and cellulose nanofibers (b); (c) SEM image of bacterial cellulose, reproduced from [227] with permission. Copyright 2017
John Wiley & Sons; (d) SEM image of oriented cellulose nanofibers based microfiber (inset: 2D XRD pattern), reproduced from [233] with permission. Copyright 2014
Hakansson et al. licensed under CC BY 4.0; (e) photo and optical microscopic image of iridescent cellulose nanocrystal film, reproduced from [235] with permission. Copyright
2014 American Chemical Society; (f) transparent cellulose nanofibers nanopaper, reproduced from [238] with permission. Copyright 2009 American Chemical Society; (g)
photo of large-area bacterial cellulose hydrogel, reproduced from [246] with permission. Copyright 2016 American Chemical Society; (h) weight-light and anisotropic aerogel
nanocellulose aerogel, reproduced from [249] with permission. Copyright 2012 Springer Nature.
16 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
microscopy, scanning electron microscopy, and atomic force
microscopy [17]. These LC structures can be preserved (frozen)
in solid films to provide a brightly iridescent structural color
(Fig. 13e) [235]. This structural color is controlled by the helical
structure as determined by the inter-distance (pitch, P) between
adjacent layers, and the observing angel (u). These terms follow the
rule l = 2npsinu, where n is the refractive index of the cellulose
film, and u is the reflection angel with respect to the film surface
[235]. Additionally, helical nanostructures in CNC films can be used
as chiral templates for inorganic nanoparticles for flexible photonic
materials [236].
Nanocellulose papers are usually prepared by vacuum assisted
filtration of a nanocellulose dispersion [237]. The optical trans-
mittance of nanocellulose papers is highly dependant on nano-
cellulose size and orientation. For CNF papers with randomly
distributed nanocellulose nanostructures, transmittance largely
increases with decreasing the diameter of nanocrystals. When the
diameter is significantly smaller than the light wavelength, the
nanopaper exhibits transmittance of 90% at 550 nm due to the
remarkably low light scattering (Fig. 13f) [238]. Additionally, the
mechanical properties of paper are highly sensitive to the diameter
of nanocellulose [239]. Nanopapers made up of ultrafine CNFs can
overcome the conflict between strength and toughness in
conventional materials. When the average diameter of nano-
cellulose decreases to 11 nm, both the strength and toughness of
the nanopaper increase by two orders of magnitude [239]. These
results suggest that smaller nanocellulose diameters can lead to
stronger and tougher nanopapers with superior properties.
Additionally, it has been demonstrated that CNFs ultrathin films
can be fabricated via spray-assisted LbL assembly, where CNFs are
uni-directionally aligned along the spray direction as controlled by
the deposition conditions [240]. In another recent study, spin-
assisted LbL assembly was exploited for formation of mechanically
robust CNFs/silk ultrathin films with high modulus of 30 GPa and
strength of 260 MPa, having a peculiar “shish kebab” CNFs/silk
nanostructures [241]. These nanoporous films allow ultrafast
water transport combined with high rejection rate for various
organic molecules and capturing heavy metal ions.
Cellulose hydrogels are physically or chemically cross-linked 3D
networks that contain up to 90 wt% water [242]. They can be
fabricated in a variety of forms including slabs, membranes, beads,
and microspheres. Regenerated cellulose hydrogel is prepared
from the cellulose solution via a sol-gel process and mainly consists
of amorphous cellulose, which is much weaker than the native
crystalline nanocellulose. In contrast, the nanocellulose hydrogels
are prepared from the nanocellulose dispersion by gelation [243].
The gelation involves physical entanglements, noncovalent inter-
actions (hydrogen bonding, ionic interaction, and van der Waal
forces) and covalent crosslinking. Cellulose nanofibers prepared by
TEMPO method will gel spontaneously when the concentration
exceeds 1 wt% [230], while the CNC dispersion has to have a several
times higher concentration to form the hydrogel due to the high
aspect ratio of CNF, enabling the more efficient physical
entanglement.
Adding other crosslinkers can significantly decrease the
requirement for the minimum nanocellulose concentration to
form hydrogel, and the mechanical properties also can be largely
enhanced. For example, metal ions were explored to induce the
gelation of nanocellulose because of the presence of negatively
charged carboxyl and sulfate groups [244,245]. Freestanding
transparent carboxylated CNF hydrogel can be prepared by using
divalent or trivalent cations (Ca2+, Zn2+, Cu2+, Al3+, and Fe3+) as
crosslinkers to form interconnected porous nanofibril networks
[244]. The storage moduli of these hydrogels are strongly
dependent on valency of the metal ions and can vary within a
wide range from 3 KPa to 31 KPa. Notably, several culturing-
specific bacteria can produce nanocellulose hydrogels directly
from low-molecular weight sugar (Fig. 13g) [246]. Compared with
the CNF and CNC hydrogels, bacterial nanocellulose hydrogels
show many advantages, including facile processing, large-scale
production, and mechanical robustness. However, their optical
transmittance is much lower than TEMPO oxide-nanocellulose
hydrogels because of their larger diameter.
Cellulose aerogels are flexible and robust porous ultralight
material with a typical porosity of 98% and density of ca.
0.03 g cm—3, and are formed when water-content in a hydrogel
is replaced with air via freeze-drying [247]. The porosity, pore size,
and pore orientation of aerogels can be regulated via controllable
drying. For instance, in the ice templating approach, when the
hydrogel is exposed to a controllable temperature gradient,
unidirectional ice crystals will form in the hydrogel and the
nanocellulose will be concentrated between ice crystals. After
removal of ice crystals by freeze drying, the anisotropic cellulose
aerogels can be prepared and the microstructure with different
dimensions can be achieved by adjusting freezing kinetics [248].
For example, cellulose aerogels with honeycomb structures were
fabricated by a unidirectional freeze-drying approach (Fig. 13h).
Even after adding other components such as GO sheets, the aerogel
can still maintain a uniform anisotropic morphology and open
microchannels [249].
5.2. Current and emerging applications of nanocellulose materials
Due to the good biocompatibility, biomedical applications of
nanocellulose materials are widely reported and well-reviewed
recently, including tissue scaffolding [250] and drug delivery
applications [251]. Additionally, nanocellulose materials possess
abundant functional groups and ultrahigh surface area, making
them attractive materials for waste water treatment, such as
removing metal ions [127], removing organic pollutants [252], and
separating oil/water phases [253]. The approaches for these
applications are well established and several reviews summarize
recent progress [254–256]. Therefore, here we mainly focus on the
emerging applications for structural nanocomposite materials,
health monitoring, energy harvest and storage, and optical and
electronic bioenabled devices.
Compared with other biopolymer components widely exploited
for bionanocomposites, such as proteins and DNA, nanocellulose
demonstrates the critical advantages in overall mechanical
performance, chemical and thermal stability, robust functionali-
ties, easy availability, and modest cost, and easy processing, which
are extremely important for their applications. For example, the
strength of nanocellulose paper is higher than 200 MPa [257],
which is several times higher than comparable protein films
(below 100 MPa for regenerated silks)[258]. Moreover, from a
nanomanufacturing viewpoint, unlike many other biological
solutions and dispersions [259], nanocellulose dispersions show
excellent shelf-life over many years and can be processed within
harsh conditions, such as different and extreme pHs, intensive
sonication, and stirring.
5.2.1. Structural applications
In the emerging applications, the nanocellulose nanocompo-
sites should satisfy very diverse and strict mechanical require-
ments. For example, bioelectronic devices applied on human skin
or embedded in some tissues (such as brains, teeth and eyes)
require mechanical compatibility (similar compliance and
strength), conformability to biological surface and high tolerance
by body. All three are necessary to ensure bioelectronic devices’
long lasting functionality and integrity. Various parts of the human
body possess very diverse mechanical properties with the elastic
modulus ranging from 1 KPa for the prostaglandin to 80 GPa for
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
teeth, which represents a significant challenge for matching with
existing bionanocomposite implants [260–263]. To integrate
bioelectronic devices into humans for detection or therapy
purposes these mechanical properties must be closely matched.
For instance, remarkable properties of human skin include its
exceptional flexibility, foldability, and stretchability (up to 30% of
elongation). These unique properties enable skin to accommodate
body movements and protect inner organs and bones against
external impacts [264]. Besides, skin has excellent sensing
functionality that not only can detect the tiny vibrations in the
external environment such as a gentle breeze and insects’
movement, but also reveal the biological changes in our body
such as the body temperature variation and sweat constituent
variation. To create artificial nanomaterial designs that match
these unique properties, it will require the electronic skin (e-skin)
materials that has matching strength, stiffness, toughness, and
flexibility to that of skin on the human body. Natural polymers
possess wide mechanical variation, depending on their molecular
structure, degree of polymerization, and constituent chemical
components which can be instrumental in solving this issue.
Moreover, combining biological components with other func-
tional synthetic components is one conventional approach for
constructing variable mechanical properties and facilitate added
functionality to the resulting materials. Notably, the most widely
used strategy is the incorporation of stretchable or compressive
components to provide the biomaterials high extensibility and
compressibility. For example, bionanocomposites composed of a
rubbery polymer matrix and rigid CNCs demonstrate a reversible
change with tunability within a wide range of the elastic moduli
when exposed to environments that can mediate CNC interactions
[265]. Functional biopolymers can be embedded into an elasto-
meric synthetic matrix to construct soft and highly stretchable
Fig. 14. (a) The CNCs/GO nanocomposites fabricated by spin-assisted LbL assembly; (b) the mechanical performance of CNCs/GO nanocomposites with other materials; (c) the
TEM image of cross-section of nanocomposites. Reproduced from [267] with permission. Copyright 2015 John Wiley & Sons.
17
nanocomposite for sensitive e-skin [246]. Also, conventional
compressive sponges such as polyurethane (PU) foams can be
used a compressible template to support these functional
biopolymers for fabricating highly sensitive pressure sensors
[266].
In another example, robust flexible bionanocomposites can be
fabricated through LbL assembly of flexible GO sheets with stiff
CNCs component (Fig. 14) [267]. In this case, the flexible GO sheets
tightly wrap the cross-junctions of the dense interlocked CNCs.
Thus, reorientation, displacement and pulling-out of the confined
CNCs components absorb massive energy during deformation,
resulting in high mechanical performance with elastic modulus as
high as 170 GPa and strength up to 650 MPa, both being close to the
record values achieved.
Wen et al. reported the fabrication of ultrastrong nano-
composite films via evaporation-induced assembly of GO sheets
and small amount of CNCs components [268]. These films
demonstrate a good combination of mechanical performance
and electrical conductivity, such as 765 MPa and 15.6 MJ m—3 for
strength and toughness, respectively, and 1105 S/cm for conduc-
tivity. Mittal et al. utilized the engineered spider silk to crosslink
the cellulose nanofiber for constructing ultrastrong fibers with the
elastic modulus of ~ 55 GPa, strength at break of ~ 1 GPa, and
toughness of 55~ MJ m—3 [269].
Controllable porosity and wide pore size distribution play an
important role for the mechanical and transport properties of
nanocellulose-based bionanocomposites. Among manufacturing
approaches, the unidirectional freeze-drying route or 3D printing
allow for the fabrication of unique materials with controllable
mechanical performance [199,249]. Strong and highly anisotropic
aerogels can be constructed through ice-template freeze-casting
suspensions of cellulose nanofibers, GO and sepiolite nanorods,
18 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

which show excellent combustion resistance and low thermal
conductivity of 15 mW/m/K [270]. Even at 30 ○C and 85% relative
humidity, the foams retained their shape and more than half of
their initial compressive strength. Notably, individual CNCs
demonstrate excellent mechanical properties, and their use is
regarded as a promising alternative for use in bulletproof armor
[271]. However, it is difficult for CNCs to retain their properties
when these nanoscale components are combined with synthetic
components into bulk materials. Overall, the mechanical perfor-
mance of nanocellulose microfibers is still lower than composites
fabricated from commercial structural fibers from Kevlar and ultra-
high molecular weight polyethylene (UHMWPE) materials [233].
Finally, the small-scale production and high cost of nano-
cellulose components are bottlenecks for commercial structural
applications even if the raw source availability is abundant that
limits their applicability in large-scale massive structural appli-
cations. Nanocellulose materials currently have no advantages
over natural wood materials in traditional building applications in
terms of both supply and price, although they are superior in terms
of mechanical performance in specifically crafted nanomaterials
with controlled assembly of nanocomponents. Therefore, the
application of nanocellulose materials in the massive structural
applications remain a grand challenge that needs more efforts to
address.
5.2.2. Optical applications
Nanocellulose-based optical devices include light and colori-
metric monitoring of the biophysical, chemical and biological
changes with Raman, fluorescence, and UV–vis spectroscopies. For
instance, surface enhanced Raman Scattering (SERS) has the
capability of non-destructive and single-molecule sensitive
detection of analytes with noble metal nanostructures as active
substrates [272–274]. Compared to traditional glass and plastic
film SERS substrates, nanocellulose substrates show many
advantages, including strong interfacial interaction with nano-
particles, high specific surface area, and flexibility [222]. In a recent
study, Singamaneni et al. [275] reported a novel BNC film-based
SERS nanocomposites that combined BNCs and gold nanorods.
Gold nanorods were uniformly and densely absorbed on the BNC
surface across entire substrate, enabling the large SERS enhance-
ment and the detection of 1 nM rhodamine (R6G) and bacteria.
In addition, 3D plasmonic aerogels were fabricated by
integrating metal nanorods with highly porous BNC/silk aerogels
(Fig. 15a) [175]. Unlike the relatively low SERS activity of 2D
substrate, the 3D aerogel demonstrated much higher sensitivity,
which allows detection of 10 fM of R6G. Additionally, these
bioplasmonic aerogels showed other functionalities, including
the highly efficient solar steam generation through photothermal
heating.
Plasmonic nanostructures for SERS can be formed in situ inside
of nanocellulose materials by the reduction of noble metal salts.
For instance, by simply boiling HAuCl4 infused BNC hydrogel in
sodium citrate solutions, Au nanoparticles of~60 nm in diameter
can be uniformly formed throughout the BNC matrix [276]. The
resulting composite hydrogel is densely loaded with Au nano-
particles and shows two broadened tunable localized surface
plasmon resonance (LSPR) peaks that indicates extensive con-
trolled interparticle coupling [276]. The highly porous morphology
plays an important role in enabling ensembles of plasmonic
nanoparticles that existing suspension-based SERS systems are not
capable of functioning in [277]. For example, BNC hydrogels have
been demonstrated to show excellent SERS signal reproducibility
for the detection of environmental contaminants in low pH
environment [276–279]. Conventional nanoparticle suspensions
will likely uncontrollably flocculate under such conditions, and
common paper based substrate is unlikely to maintain its original
3D structure.
Because of the ubiquitous presence of hydroxyl groups on BNC
nanofibers, well dispersed Au nanocrystals sparsely populated
along nanocellulose fibers can be synthesized without the need for

Fig. 15. (a) Preparation of bacterial cellulose based plasmonic biofoam, reproduced from [174] with permission. Copyright 2016 American Chemical Society; (b) photo of
transparent and photoluminescent foldable nanocellulose/quantum dot nanopaper, reproduced from [291] with permission. Copyright 2015 American Chemical Society; (c)
photo and SEM of CNC based responsive photonic hydrogels, reproduced from [293] with permission Copyright 2013 John Wiley & Sons; (d) the preparation of near-IR-
sensitive upconverting nanostructured photonic cellulose films, reproduced from [294] with permission. Copyright 2016 John Wiley & Sons; (e) the scheme of chiral
plasmonic films nanostructure by co-assembly of CNC and gold nanorods, reproduced from [296] with permission. Copyright 2014 American Chemical Society.
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 19

external reductants [280,281]. The density and size of these Au
nanocrystals can be controlled by varying reaction time. Interest-
ingly, these BNC hydrogels form a unique multilayered 3D
structure with relatively dense ultrathin layers separated by
regular spacing of several microns [282]. Another important aspect
of such hydrogels is that upon dehydration, the nanofibers shrink
and tighten the interlock with each other, the interlayer distance
also decreases. This self-induced deformation is extremely
advantageous for SERS detection, as the porous structure of
swelled hydrogel ensure the maximum adsorption of analyte
molecule onto Au nanoparticle surface, while the subsequent
drying creates strong coupling between the plasmonic nano-
particles to form active SERS hotspots that greatly enhances the
Raman signal of molecules trapped on the nanoparticle surface
[282].
Nanocellulose materials are also exploited as a pre-formed
substrate to direct the drying of Au nanoparticle suspensions to
facilely fabricate high performance SERS platforms. In this
approach, a sessile drop of concentrated CNF solution can dry
on a glass substrate to form a uniform CNF network [283]. This
network then acts as a pre-structured host to direct the local flow
of Au nanoparticle suspensions to form a widened “coffee ring”
aggregation. Unlike the narrow “coffee-rings” formed by direct
deposition of Au nanoparticle suspensions, which can be easily
disturbed by subsequent casting of analyte solutions [284]. The
CNF-AuNP nanocomposites are extremely stable, because CNF
network cannot be re-dissolved. Coupled with CNF’s low Raman
background, the method results in highly sensitive (pM) detection
limit for R6B and dopamine with excellent reproducibility [283].
Moreover, nanoparticle loaded nanocellulose materials can also
be used as a disposable colorimetric sensing platform. Plasmonic
nanopapers produced via in situ synthesis of Ag and Au nano-
particles in BNC platforms have been demonstrated to display
sensitivity to specific types of chemicals [275]. For example, thiol
compounds such as methimazole can act as a molecular linker and
promote Ag nanoparticles in the BNC platform to aggregate,
inducing plasmon coupling and color redshift. A similar chemical
induced aggregation and color changes can be observed when Au
nanoparticle-BNC materials are exposed to thiourea, cyanide and
iodine. The chemical etching effect will cause the Ag nanoparticles
to shrink, resulting in detectable blue shift.
Nanocellulose components can be used as templates to
construct advanced chiral plasmonic nanostructures [285–287].
Recently, both electron tomography and AFM studies have shown
that individual CNC rods are twisted along their axial in the right-
hand direction [17]. These unique molecular structures can be
utilized to assemble plasmonic nanocrystals that align along the
twisted nanocrystals. Resulting nanostructures display chiral
plasmonic properties at the single nanocrystal level. The actual
application of this principle is, however, more intricate. In practice,
cationic spherical Au nanoparticle can be assembled on sulfate
ester surface groups [285,286]. The chiral optical properties of the

Fig. 16. (a) Photographs and SEM images of neat CNC and CNC/PEG composite films; (b) Photograph and transmission spectra showing the reversible color change of CNC-2/
PEG (80/20) composite film in (a) under different relative humidity, reproduced from [300] with permission. Copyright 2017 John Wiley & Sons. (c) Color changes of MPC films
soaked in EtOH/H2O mixtures of different ratios; (d) Pressure induced color change of MPC film. Reproduced from [301] with permission. Copyright 2014 John Wiley & Sons.
20 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

assembled structures are closely related to the size of the
nanoparticle. If the nanoparticles are too large compared to the
diameter of CNCs (= 7 nm), the size mismatch will prevent the
nanoparticles to follow the chiral twist of the CNC, yielding achiral
structures. When nanoparticles of 8.5 nm diameter are used, chiral
structures (30–60 nm in lateral dimension and 200–500 nm in
length) displaying strong circular dichroism (CD) signals can be
obtained [287].
Quantum dots, highly fluorescent semiconductor nanocrystals,
have drawn increasing attention due to their prospective
applications in optical materials, biosensors, biomedical imaging,
marker development, and anticounterfeiting [288]. Various types
of quantum dots were incorporated onto the nanocellulose
surfaces to fabricate transparent, smooth, and fluorescent nano-
paper materials. For example, carbon quantum dots that are low
toxic, nanosized, luminescent, and easy to functionalize, can be
covalently attached to cellulose nanofibers via covalent coupling
[289,290]. Water-soluble ZnSe quantum dots modified by positive
charged polymer were added to the cellulose nanopaper surface by
vacuum assisted filtration [291]. As shown in Fig. 15b, the as-
prepared nanopaper shows high optical transmittance and high
intensity photoluminescent performance.
CNC films demonstrate iridescent structure color due to their
long-range chiral nematic ordering, which showed great potential
for bio-optical devices, such as displays and biosensors [292].
When exposed to various external environments, the pitch of
helical structures will change, leading to the variation of structural
color of CNC films. It was reported that a responsive nano-
composite hydrogel can be prepared by assembly of CNCs with
various hydrogel materials (Fig. 15c) [293]. These new chiral
hydrogels demonstrated tunable colors, respond to various stimuli,
including pH and solvent and temperature, resulting in the
variation of pitch.
Additionally, chiral nematic structures formed by CNCs have
garnered attention as either an LC template or as a host for
developing active optical materials, if CNC components are
combined with other nanoparticles (gold, silver, and rare earth)
[226]. For example, flexible photonic nanocellulose films were
fabricated by helicoidal co-assembly of CNCs with NaYF4:Yb,Er
hexagonal nanorods [294]. These films showed not only upcon-
version with near-IR light, but also retained tunable photonic chiral
activity (Fig. 15d). This approach has been extensively used for the
alignment of Au nanorods of different sizes and aspect ratios. Au
nanorods co-dispersed in nematic phase show orientation of Au
nanorods with the increase in CNC concentration [295]. The
resulting film showed a distinct polarization-dependent extinction
profile with the longitudinal and transverse mode of Au nanorods
separately excited. Au nanorods co-dispersed in chiral CNC phase
follow the orientation of CNCs in each layer and are arranged into a
helical configuration (Fig. 15e) [295,296].
The structural color of CNCs in liquid crystal phases can be
selectively modified by changing the spacing between each CNC
layer. This can be achieved by the co-assembly of CNC with another
compatible component such as various hydrophilic polymers
[297–299]. For example, CNC can be self-assembled with poly
(ethylene glycol) (PEG) into uniform interlayered helical structure
while retaining its chiral nematic phase [300]. The pitch size of the
multilayered structure can be controlled by the relative ratio of the
two components, producing different structural iridescence
(Fig. 16a). Depending on the polymer component incorporated,
composite films like this can have many interesting properties. For
instance, since PEG has high affinity towards water molecules,
CNC/PEG composite films will have different water absorbing
capabilities depending on the relative loading of PEG. More
importantly, the infiltration of water causes the PEG layer to swell
and changes the pitch size, hence color, of the cholesteric structure,
yielding stimuli responsive color changes (Fig. 16b) [300].

Fig. 17. (a) Comparison of transparent cellulose nanopaper and regular paper, reproduced from [305] with permission. Copyright 2009 John Wiley & Sons; (b) photo of a CNF
decal transfer with conductive traces conforming to an epidermal surface, reproduced from [315] with permission. Copyright 2014 John Wiley & Sons; (c) photo of organic
solar cell fabricated on CNC substrate, reproduced from [317] with permission. Copyright 2013 Zhou et al. licensed under CC BY 4.0; Photo and optical microscopy image of
transparent nanopaper-based organic light-emitting diode array (d), reproduced from [321] with permission. Copyright 2013 John Wiley & Sons, and gallium arsenide
microwave devices (e), reproduced from [29] with permission. Copyright 2015 Jung et. al licensed under CC BY 4.0.
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 21

The polymer can also act as a co-template for the construction of
mesoporous photonic cellulose (MPC) films. In one example of this
set up, CNC and urea–formaldehyde (UF) precursor are first co-
assembled into a chiral nematic structure, the interlacing UF is
then cured into a resin. A subsequent KOH etching step removes
the polymer network and produces a porous structure of CNC with
preserved nematic order [301]. Apparently, the structural color of
MPC film is highly sensitive toward the chemical nature of the
solvent. By simply varying the mixture ratio of EtOH/H 2O, the
difference in induced swelling can shift the transmission peak from
430 nm (pure EtOH) to 840 nm (pure H 2O) (Fig. 15c). Due to its
porous structure, the application of different pressure on MPC
films in the macroscopic level can be directly transferred to the
change in pitch size, making the film piezochromatic [301]. The
color change is completely reversible, suggesting potential
applications in facile color based pressure sensing.
5.2.3. Electronic biodevices
Flexible wearable electronic devices are in a high demand for
various sensing and monitoring applications [302–304]. Although
nanocellulose materials are not electrically conductive, they can
play the role in the electronic devices either as non-active (e.g.,
supporting substrates) or active components after adding conduc-
tive additives.
5.2.3.1. Nanocellulose as flexible and transparent substrates for
electronic devices. Flexible substrates play an important role in
the flexible electronics as a major component, which determines the
mechanical, optical, and portable robustness. Compared with
traditional flexible substrates for electronics including plastic film
and regular paper, cellulose nanopaper demonstrates unique
advantages for these applications. Their excellent mechanical
properties ensure the stability of devices even after numerous
bending and folding, while the high optical transmittance facilitates
transparency of flexible devices (Fig. 17a) [305]. Moreover,
nanocellulose papers possess much lower coefficient of thermal
expansion (CTE) < 8.5 ppm/K than plastic (CTE,~ 50 ppm/K) [306].
Their smooth surface with low roughness and high degradation
temperature allows the fabrication of high resolution electronic
patterns even at high temperature environment. In the past years,
various electronic devices were integrated on these substrates,
including solar cells, transistors, organic light-emitting diodes
(OLED), antennae, and touchscreens [307–310].
Conductive circuits can be integrated on various substrates by
writing, printing, and vapor deposition (CVD). In the previous
decade, regular cellulose papers were widely used as substrates for
patterning various conductive components such as graphene [311],
CNT [312], silver nanoparticles [313] and conductive polymers
[314]. However, the emergence of transparent cellulose nanopaper
materials can facilitate the fabrication of flexible and transparent
conductive circuits with high resolution. Recently, novel conformal
electronic decals based on a CNF and pullulan bi-layer structure
were reported [315]. In the approach, the circuit board on CNF layer
can be fabricated on targeted surfaces with complicated topogra-
phy such as human skin or flowers (Fig. 17b). Additionally, these
transparent conductive materials can be deposited on the nano-
papers to prepare highly electrical conductive substrates for the
electronic integration.

Fig. 18. (a) Nanocellulose based ionic diode, reproduced from [325] with permission. Copyright 2012 American Chemical Society; (b) scheme of preparation of CNC aerogel
based supercapacitors, reproduced from [326] with permission.Copyright 2015 John Wiley & Sons ; (c) the scheme of the formation of proposed core–shell PPy coated CNC.
PVP was adsorbed onto the CNC surface prior to the polymerization to promote the homogeneous growth of PPy shell and the responding TEM images, reproduced from [327]
with permission. Copyright 2014 Royal Society of Chemistry; (d) scheme of LbL assembly of the CNF aerogel based energy storage materials, reproduced from [328] with
permission. Copyright 2013 John Wiley & Sons.
22 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
The solution processing of bionanocomposites allows solar cells
to be constructed on large-area substrates [316]. For instance,
Kippelen et al. reported that polymer solar cells can be fabricated
on optically transparent CNC substrates, which showed good
rectification in the dark and good conversion efficiency (Fig. 17c)
[317]. Notably, these solar cells on the CNC substrate will
disintegrate when exposed to water at room temperature.
On the other hand, CNF-based nanopapers have better
flexibility than the rigid CNC paper [318]. Recently, foldable solar
cells were fabricated by integrating organic cell components on the
transparent conductive nanopaper substrates [319]. The conduc-
tivity of the transparent nanopaper from CNFs and silver nano-
wires almost unchanged after repeated multiple foldings.
Moreover, solar cells integrated on the nanopaper exhibited a
power conversion efficiency of 3.2%, comparable with ITO glass-
based solar cells.
Flexible organic field-effect transistors with high transparency
fabricated on nanopapers demonstrated outstanding transmit-
tance and flexibility [320]. Flexible CNTs were introduced on the
nanopaper as a gate component. The good compatibility between
polymer and cellulose nanopaper allows only a 10% decrease in
mobility when experiencing bending or folding, while maintaining
high optical transmittance. In another study, Fujisaki et al. [321]
successfully fabricated large-area organic transistor array on a
nanopaper by lithographic and solution-based processes (Fig. 17d).
These flexible transistors benefited from the ultra-smooth surface
of nanopaper and exhibited a high hole mobility of up to 1 cm2/V/s.
Zhu et al. [322] manufactured OLED devices on transparent
nanopaper, which exhibits very little difference in terms of — JV
curve before and after bending. Jung et al. [29] reported large-area
gallium arsenide microwave devices deposited on nanopaper (Fig.
17e). These devices demonstrated comparable performance to their
rigid counterparts, and can be biodegraded by fungi. Other
electronic devices such as touch screens, touch sensors and
antennae can also be efficiently constructed on the nanopapers
[310,323,324].
5.2.3.2. Nanocellulose as active components in the electronic
devices. To function as active components in electronic devices,
nanocellulose materials should be modified to obtain acceptable
electrical conductivity. These modifications involve surface
grafting, in-situ growth, post-coating, and blending of
conductive components such as conductive polymers, carbon- based
materials and metal nanoparticle. For example, Zhang et al.
[325] used a two-step (oxidation and sulfonation) method to
produce negatively charged cellulose nanofibers, while positively
charged cellulose nanofibers were prepared by grafting quaternary
ammonia salt. These two types of cellulose nanofibers were
successfully integrated into a new biopolymer based ionic diode
device, where cations and anions can selectively transport under
positive and negative bias due to the different charged cellulose
nanofibers (Fig. 18a).
Various conductive materials were incorporated with nano-
cellulose to construct a wide range of electronic devices form
supercapacitors to biosensors. Yang et al. [326] demonstrated that
CNC aerogel can act as a universal support for various conductive
components to fabricate flexible light-weight supercapacitors with
high performance. The combination of two kinds of CNC with
NHNH2 and— —CHO functionalities will induce the gelation of CNCs
by chemical bonding (Fig. 18b). During the gelation, polypyrrole
nanofibers (PPy-NF), (B) polypyrrole-coated CNTs (PPy-CNT), and
(C) spherical manganese dioxide nanoparticles (MnO2-NP) can be
incorporated into this system. After the freeze-drying, these hybrid
aerogels can be used as supercapacitors and show excellent
capacitance retention at high charge–discharge rates due to their
high porosity and uniform 3D morphology.
In another study, Wu et al. [327] used poly(N-vinylpyrrolidone)
(PVP) coated CNCs as templates to in-situ polymerize polypyrrole
(PPy). These PPy uniformly coated CNCs surface to form a well-
defined core–shell structure. As shown in Fig. 18c, the size of the
PPy modified CNC significantly increased and no aggregation was
observed. These highly uniform PPy-CNC nanostructures exhibit
largely enhanced electrochemical performance with an outstand-
ing conductivity of 36.9 S/cm, specific capacitance of 323 F/g and
excellent cycling stability.
In an alternating approach, Hamedi et al. [328] explored LbL
assembly of poly(3,4-ethylenedioxythiophene):poly(styrenesulfo-
nate) (PEDOT:PSS) and sodium poly[2-(3-Thienyl)ethoxy-4-butyl-
sulfonate] (ADS2000P), and single-wall CNTs (SWCNTs) on the
chemically crosslinked cellulose nanofiber aerogel surface to
fabricate charge storage devices (Fig. 18d). Benefiting from the
high porosity close to 99%, supercapacitors fabricated from these
aerogels show excellent specific capacitance values up to 400 F/g,
exceeding the best reported CNT based supercapacitors. In another
recent work, the authors used the same method to fabricate
compressible interdigitated thin-film supercapacitors and batter-
ies by using nanocellulose materials as templates [329].
5.3. Other polysaccharides: brief introduction
5.3.1. Chitin and chitosan
Chitin is the second most abundant biopolymer produced by
nature after cellulose, and can be found in marine crustaceans,
shrimp and crabs. Chitins are known to be cellulose analogues with
a (1,4)-b-N-acetyl glycosaminoglycan-repeating structure (Fig. 1)
[330]. Naturally occurring chitin shows highly ordered crystalline
microfibrils for constructing these structural components in the
exoskeleton of arthropods or in the cell walls of fungi and yeast to
provide structural integrity and protection [331]. To obtain pure
colorless chitin, natural chitin sources are treated by acid and
alkaline in order to remove the calcium carbonate and soluble
protein components, respectively. A decolorization step further
removes residual pigments. Chitin is basically insoluble in
common solvents such as water and organic solvents due to the
hydrogen bonded structures similarly to nanocellulose.
Ionic liquids and NaOH/urea were found to be good solvents for
both cellulose and chitin [332,333], and thus can be used to
prepare various chitin materials, including fibers, films and
aerogels. By partial deacetylation under alkaline conditions,
chitosan can be obtained, which is the most important chitin
derivative. The NH2 groups on the chitosan backbones provide
positive charges, enabling the good solubility of chitosan in the
slightly acidic water. Additionally, these positive charges also
provide the possibility for the interfacial strength enhancement
through the strong electrostatic interactions. Notably, native chitin
nanofibers can also be obtained from natural sources by simple
mechanical treatment after the removal of proteins and mineral,
such as grinding [334], ultrasonication [335] and high pressure
homogenization [336].
The elementary chitin nanofibers might have a diameter of 3–
4 nm [335], although the majority of these nanofibers have a
diameter of 10–100 nm [334,337,338]. Besides, chitin nanocrystals
can be prepared by acid hydrolysis of amorphous domains of
semicrystalline chitin. Chitin nanofibers also possess excellent
mechanical performance and their film are highly transparent,
ultra-smooth, and electrically insulating. For example, Jin et al.
[339] demonstrated the chitin nanofiber paper prepared from
squid-pen can be used as transparent flexible substrate for OLED.
Hosseini et al. [340] reported a flexible and transparent resistive
switching memory chips based on chitosan films, which is
biodegradable and decomposable when exposing to water.
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5.3.2. Alginates
Alginate is an anionic biopolymer typically extracted from
brown seaweed by alkali treatment, and widely used in the
biomedical applications because of its good biocompatibility, low-
cost and easy-processing [341]. It is a linear copolymer with blocks
of (1–4)-linked b-D-mannuronate (M) and a-L-guluronate (G)
residues, covalently linked together in different sequences, and its
chemical structures highly depends on the natural sources (Fig. 1)
[342]. Alginate is a water soluble biopolymer, which can be
crosslinked by the divalent cations such as Ca2+ for preparing the
hydrogel because of the presence of abundant carboxyl groups in
the molecular chains [343].
The compliance that matches the extracellular matrices of
living tissues enables applications in wound healing, drug delivery,
and tissue engineering. For example, alginate hydrogels can
preserve a stable, moist environment for wound tissue healing
to minimize infection risk [344]. Some active agents or anti-
bacterial drugs can also be incorporated into the hydrogel to
further facilitate the wound healing [345]. Alginate can act as a bio-
surfactant for dispersing various nanoparticles, such as graphene
and 2D transition metal dichalcogenides, for providing them
enhanced biocompatibility and interfacial strength with other
matrices. For example, Zong et al. [346] reported that sodium
alginate can high efficiently exfoliate and disperse the tungsten
disulfide (WS2) nanoplates to obtain stable dispersions. Then,
tough and strong bionanocomposites can be fabricated from this
dispersion, which demonstrated good multi-responsive response
to humidity and light. Kovalenko et al. demonstrated that the
combination of Si nanopowder with alginates can result in a stable
anode possessing reversible capacity eight times higher than that
of conventional graphitic anodes [347].
6. Proteins for bionanocomposites
Primary configurational protein structures or protein sequences
usually fold and interweave to form secondary structures with
ordered components such as beta sheet, turns, and helices, as well
as amorphous coils [48]. Further assembly yields one of four
Fig. 19. Key hierarchical structural features of Bombyx mori silkworm cocoon silk (a), reproduced from [349,352] with permission. Copyright 2013 John Wiley & Sons,
Copyright. Copyright 2003 Springer Nature; and spider silk (b), reproduced from [48] with permission. Copyringht 2010 Springer Nature.
23
common tertiary structures: fibrous, globular, membrane, and
disordered. Disordered and globular proteins tend to function as
enzymes or catalysts. Membrane proteins facilitate transport of
species between extracellular matrices and carriers.
Fibrous proteins offer reinforcement and elasticity to tissue and
bone. In human skin, collagen fibers confer toughness and
flexibility [348]. Fibrous proteins derive their strength from a
hierarchical micro/nano morphologies [259]. This mix of strength,
biocompatibility, and facile processing have made fibrous proteins
a common additive in biocomposites for a range of applications
from actuating soft materials and flexible electronics to drug laden
scaffolds. Silk materials have been thoroughly studied with respect
to each attribute, so this example will be the focus in following
discussion of respective bionanocomposites.
6.1. Overview of silk: source and structure
Natural silk is a fibrous protein expressed by many arthropods
including spiders, silkworms as well as flies and silverfish. Each
arthropod produces silk with different amino acid structure and
different propensity for beta sheet, helical, and amorphous
structures (Fig. 19a and b) [349–352]. The spider’s major
ampullated spidroin functions as a high modulus dragline
preventing insect prey from falling. It consists of mostly glycine
and alanine residues. The alanine portions stack to form b-sheet
crystals while glycine introduces amorphous structure and
conformation. Fibers from the minor ampullate consist of non-
repetitive, conserve C and N termini peptides dominated by glycine
and alanine dominant non-repetitive central sequence [353]. This
structure confers the fiber tensile strength and extensibility
needed to wrap and preserve prey.
Factors such as the source, arthropod’s diet, and living
environment also effect silk properties. Commercial silks used
in textiles is produced by Bombyx mori, or mulberry silkworms,
then extracted and wound into fibers. When Nicodemo enriched
the leaves with specific amino acids like valine and threonine prior
to silkworm consumption, silkworm mortality and cocoon weight
was relatively unchanged [354]. However, the silk produced by
24 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
silkworms on the amino acid enriched diets had higher tensile
strength than those fed untreated Mulberry leaves [355]. Similarly,
feeding the silkworms spray dyed leaves produces silk cocoons of
the same color. Some groups have even engineered graphene and
nanoparticle containing silks by feeding the silkworms leaves
coated in the desired filler or active agent [74].
Within the arthropods, silk production is impacted by
physiology, spinning speed, and cytology. Environmental con-
ditions would conceivably affect the organism’s health and thus
physiology. Spiders tend to move faster under high temperatures
and spin silk faster. Increased reel speeds then lead to fibers with
higher tensile strength and narrower diameters [356]. Upon
extrusion, spider silk fiber dimensions and strength were
influenced by temperature [351]. Additionally, humidity can also
alter silk properties by facilitating rearrangement under high
humidity and locking in the initial extruded conformation via
dehydration [356].
Although, many insects produce silk, Bombyx mori and Nephila
clavipes are the easiest to obtain and extract silk [350,357]. Spiders
have six silk glands, two each at their anterior, median, and
posterior. At these silk glands, the aqueous dope resides as a liquid
crystalline solution prior to fiber forming during extrusion. Spiders
produce tubuliform silk as a protective coating for egg sacs,
aciniform silk to wrap prey and egg sacs, course flagelliform fibers
to capture prey on orb webs, piniform to anchor non-silk surfaces,
minor ampullate to coat as a non-sticky web scaffolding, and major
ampullate to act as a safety line.
Silk from the Bombyx mori starts in the same state as an aqueous
suspension of proteins and ions silkworm glands [349–351]. The
silkworm forces this suspension out through a spigot in a figure
eight to form the many layers of its cocoon (Fig. 19a). This cocoon
insulates the silkworm from temperature and humidity fluctua-
tions, protects it from ultraviolet rays, bacterial and fungal threats
as well as predators. A closer look at the cocoons shows silkworm
silk derives tensile strength from its semi-crystalline structure,
imperviousness from densely layered cocoon microstructure, and
resistance to radiation to protein based coatings on the fibers.
Silkworm fibers are 10–25 um in diameter and consist of two
fibroins bound by hydrophilic gumming proteins and sericins
which comprise 25–30% of silk cocoon mass [358]. The fibroin
reduces to many fibroin fibrils of silk molecules of glycine (43%),
alanine (30%), and serine (12%) [359]. The fiber structure resembles
a hydrophobic co-polymer with alternating 390 kDa heavy chain
and 25 kDa light chain sections joined by one disulfide bond with
each comprising an equal proportion of the fiber [360]. The heavy
chain forms the crystalline fiber regimes with aliphatic amino
acids glycine and alanine assembled into a series of hexapeptides:
GAGAGX or GAGXGA, where X is alanine (A), serine (S), valine (V),
tyrosine (Y), and threonine (Thr). GAA or GAGS cap the subdomains
(Fig. 19a) [349].
Aliphatic amino acids make up this section, rendering it
hydrophobic. Poly(alanine) in major ampullate spidroin, the
hydrophobic GAGAGX portion, produces anti-parallel b-sheet
crystals. Non-repetitive peptides intersperse up to 12 domains of
the hexapeptides [361]. Eleven non-repetitive light chains link 12
heavy chain domains. The light chain has 25 amino acid sequence,
consisting of proline, charged residues lysine and arginine, and
tryptophan. Charged residues lend the domain hydrophilicity,
while proline introduces turns that wind its mix of helices, beta
sheets, and turns into an amorphous globular linkage between
crystalline domains [361]. Single cysteines form disulfide linkages
between the heavy and light domains.
Spider silk fibers consist of a fibroin encased in gumming
protein [362]. Each fibroin is a several micrometers wide bundle of
fibrils where hydrophobic sections of the protein primary structure
have assembled into nanocrystals nestled between neighboring
amorphous sections (Fig. 19b) [48]. The hierarchical, semi-
crystalline fibers exhibit non-linear stress-strain behavior as their
ordered structure unfolds in response to strain. In the Nephila
clavipes orb weaving spider, the semi-crystalline structure is
formed by ordered poly(alanine) stretches mixed with beta-turns,
and amorphous spacers. GPGQQ subsections create beta-turns
while GGX sections, where X is glutamine (Q), tyrosine (Y), and
leucine (L), form 310-helices. The b-turn which form spirals and
helical sections are not as common in silks from other species,
allow spiders to make more flexible silks for applications where
toughness is less needed than in dragline silk. The spider silk fibers
are usually obtained by direct extraction from a spider, drawing
from their spinneret, or expression from E. coli.
Silks have three common polymorphs: coiled silk I, b-sheet
crystalline silk II, and helical silk III [358,363,364]. Glandular silk
has secondary structure of silk I. This is characteristic of silk ex vivo
solution state. Mechanical stress like stretching or shear as well as
heating cause a transformation to silk II polymorph. The shear and
pulling endured during spinning from the silk gland cause this
shift. Solvents and buffers can be used for the same effect [365].
The silk II b-sheets exhibit strong inter and intramolecular
hydrogen bonding and van der Waals interactions. This polymorph
is largely insoluble and requires treatment with chaotropic agents
for processing. The abundance of inter and intramolecular bonding
in the silk II polymorph contributes strength and stability under
heat.
Though, Bombyx mori cocoon and Nephila clavipes dragline silk
boast high toughness and extensibility, spider major ampullate
spidroin is the strongest and most extensible silk available with
tensile modulus comparable to Kevlar and greater strength to
density ratio than steel [366,367]. Major ampullated spidroin is
often harvested from spider glands then rinsed copiously to
remove the gummy outer layer. Artificial spider silks are available
but expensive and usually are not comparable to the natural
products.
Bombyx mori silk production is a centuries old industry that
produces millions of pounds of silk per year [368]. Though inferior
to major ampullated spidroin, silkworm silk is still one of the
strongest natural fibers available that makes silkworm silk the
most commonly used silk in research and the most economical
choice for composite-based devices. Thus, further discussion of silk
structure, properties and processing will focus predominantly on
the more abundant Bombyx mori silk. Although spider and
silkworm silks differ compositionally, their higher order structure,
properties, and processes are similar with some major differences
to be noted.
6.2. Processing of silk: extract, chemical and non-chemical
manipulation
Processing can affect silk structure and ultimately the silk
properties. Fundamental studies have been conducted on untreat-
ed silk fibers to establish current understanding of the natural
fibers. However, for composites, the silk protein is typically
extracted and treated to facilitate aqueous processing [350]. First,
silk cocoons are boiled in an alkaline solution to extract the sericin
proteins. Cutting the cocoons or delaminating them prior to sericin
extraction can expedite this process. Sericins break down, and the
degummed silk is washed copiously to remove degraded sericin
and residual alkaline salts. Without degumming, sericin would
induce silk aggregation in solution. This process also reduces silk
molecular weight and can be used to produce silk of specified
molecular weights.
Degummed silk fibroin can be spun into fibers and ropes, cast as
a non-woven, or further treated for aqueous dissolution. The first
two processes are more common industrially and limited in
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materials research and design. Aqueous dissolution, also known as
reconstitution, opens silk to a wide array of fabrication methods;
thus, aqueous dissolution is a preliminary step for developing most
silk containing devices.
From the solution state, silk can be electrospun to form mats,
lyophilized to form porous sponges, noncovalently crosslinked to
make gels, or cast into films. Silk reconstitution begins with
dissolving silk in 9.3 M LiBr solution then dialysis against water.
LiBr is a chaotropic salt used to disrupt inter and intramolecular
hydrogen bonds inherent to the silk II structure of degummed silk
[369]. Other lithium based salts and chaotropic salt/solvent blends
work as well, however, silk is most soluble in LiBr. However, like
degumming, treatment with chaotropic salts has adverse effects.
Disrupting silk-silk hydrogen bonds shifts the structure from silk II
to silk I, a weaker polymorph and less stable. To this end, Koebley
et al. reported that the dissolution process damages binding sites
that enable native silk to assemble into 1D fibers upon shearing
while reconstituted silk cannot [370].
There are a few viable alternatives to these noxious processes.
For silk harvested from silkworm glands, copious washes with
deionized water will remove sericin and produce an aqueous silk
slurry, requiring no noxious agents to achieve an aqueous silk
suspension [370,371]. Unfortunately, this method is only viable for
fundamental studies and interaction studies, not for large-scale
composites. For cocoon silk, ionic liquids used to solvate cellulose
were employed to dissolve silk prior to and after sericin removal. 1-
butyl-3-methylimidazolium (BMIM) based ionic liquids success-
fully reverted the silk II–silk I, disrupting protein-protein hydrogen
bonds [369]. BMIM with bromide counter ion did this while
dissolving sericin, showing that BMIM Br could be used to bypass
the alkaline salt and chaotropic agent treatments for degumming
and reconstitution, respectively [369].
Furthermore, methods have been established to tune silk
primary and tertiary structure in attempt to partially recover pre-
Fig. 20. (a) The effect of thermal vapor annealing on silk crystallinity, reproduced from [375] with permission. Copyright 2011 American Chemical Society; (b) Silk ionomer
electrostatic interactions on silk microcapsule fabrication, reproduced from [378] with permission. Copyright 2015 American Chemical Society.
25
processing mechanical properties. Silk assembly is primarily
controlled by shear stresses and water loss during processing,
which causes assembly of rod-like structures and branched linear
structures of native and reconstituted silk fibroin, respectively
[372]. In addition to shear and water loss, silk fibroin structure may
be tuned by chemical modification, solvent and water annealing in
order to alter hydrogen bonding and ion pairing [373,374]. By
manipulating b-sheet content, silk fibroin toughness and strain at
break can be tuned over a wide range of values. For instance, it has
been shown that exposure to alcohols, particularly methanol,
induces a rapid conformational transition from amorphous
random coils to crystallization as b-sheets thus increasing strength
but reducing ultimate strain [365].
Water as a solvent may also induce a conformational shift from
random coils to helices and b-sheets [375]. At temperatures below
60 ○C, the random coil content decreases and leads to an increase in
helices and b-sheets secondary structures. At higher temperatures
b-sheets become the dominant structure (Fig. 20a). In this method,
water molecules effectively plasticize silk fibroin to increase local
chain mobility while thermal mobility provides energy necessary
to transition from random coils to crystalline b-sheets. Initial
studies implementing this method saw silk crystallization of 60%,
the maximum achievable with silk fibroin.
Genetic engineering affords greater control of silk-based
biomaterial properties [376,377]. These methods tend to be
truncated silk-like structures primarily used for fundamental
adhesion and cell encapsulation studies. Drachuk et al. created cell
and drug capsules using alternating layers of silk modified with
lysine and glutamate (Fig. 20b) [378]. The lysine and glutamate
functionalities have opposite charges whose electrostatic attrac-
tion allow for LbL membrane assembly. Silk-like peptides modified
either with poly-lysine and poly-glutamate are used to create drug
delivery vehicles. Addition of charged amino acids and much more
is possible with silk fibroin thanks to the hydroxyl groups on
26 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
threonine, serine, glutamic acid, aspartic acid, and tyrosine
residues. However, less than 4% of silk residues contain hydroxyl
groups.
Silk is amphiphilic and contains many sites for hydrogen
bonding, van der Waals interactions, and electrostatic interactions
[48,349,350,361]. Hydrophobic species will adhere to silk surfaces.
Ionic interactions with silk fibroin are similarly mediated. For
instance, Yin et al. created laminated silk-GO composites to
capitalize on these interactions between polar silk moieties and
GO’s hydroxyl and epoxide groups. In doing so, they achieved a 6%
increase tensile modulus and three-fold increase in elasticity over
contemporary silk-GO composites [379]. The complementary
multi-domain interfacial interactions facilitated stress transfer
through the composite. The silk crystalline formation fostered via
silk-GO hydrogen bonds provided added reinforcement.
Despite the existence of many modification methods, the
performance characteristics of raw silk remains elusive. While
many methods exist for silk crystallization, few methods allow
exact control over degree of crystallinity or directionality of
crystallites [380]. However, these methods grant control over
reconstituted silk fibroin structure and interfacial interactions that
define mechanical and active performance. This control matched
with degummed silk’s biocompatibility make silk readily applica-
ble to a variety of design challenges.
6.3. Applications of silk nanocomposites
Numerous studies have shown silk’s potential utilities in a host
of applications including hydrogels, core-shell particles, tissue
scaffolds, and nanocomposites [381–388]. Highly elastomeric
natural biomaterials enable the effective load transfer between
reinforcing and functional nanoscale fillers through an array of
hydrophobic, van der Waals, electrostatic, and hydrogen bonding
interactions. Generally, silk materials serve as a matrix for reactive
and functional components with a variety of inorganic or carbon
components [389]. Optically active components lend functionality
as sensing and energy storage devices while the elastomeric
bioderived matrix confers flexibility and biocompatibility [390].
Silk also offers a matrix for nanofiller loading and adjustable
mechanical, degradation, thermal, and optical properties.
6.3.1. Biomedical applications
Biological processes on the human body such as blinking,
breathing, and renewing are highly complex processes. These
processes rely on controlled concentration gradients to send
messages along a synapse, unraveling of DNA to encode production
of new cells, and pH and thermal control to ensure key enzymes
retain their activity. Hydration, ion concentration, pH, and
hydrophobic interactions effect the hierarchical structure of our
body’s tool and processes needed for daily function. Biomaterials
must be designed to perform to their desired functions without
adversely impacting the body’s regular functions and answer some
critical questions. Does the composite match the mechanical
properties and structure of the organelle it supports? How does the
construct impact adhesion, growth, and differentiation of cells?
And, any biocomposite desired to be used in situ must be either
retrievable or biodegradable.
Fibrous proteins, particularly silks, have proven adept at
meeting these design criteria. Silk suture have been employed
as biocompatible sutures for centuries. Silk sutures elicited few
adverse reactions, and those sited have been linked sericin. When
properly degummed and sterilized, silk has proven successful in
short term uses with biocompatibility comparable polylactic acid
and collagen [391]. However, it falls short like many of its
contemporaries in extended use applications in the body. A major
immunological trigger is debris.
When biomaterials remain in the body, degradation occurs and
the degradation products become a kind of debris that set off
adverse reactions. There are many ongoing investigations into
understanding this immunologic response and how this response
is affected by the size and morphology of degradation products.
The degradation rate of reconstituted silk depends on secondary
and supramolecular structure. For example, silk fibers degrade
faster than fibroin. Wang et al. [392] reported the degradation of
3D silk scaffolds implanted in rat models within three weeks with
complete disappearance after one year. The study showed that silk
is both biodegradable and resorbable, meaning that silk will break
into smaller components that can be carried by fluid transfer and
filtrated or metabolized by the body.
Silk’s ease of modification also allows one to engineer its
degradation path and kinetics. And the same means used to control
degradation can be used to tune mechanical properties. In nature,
silk produced by the same organism can have vastly different uses
and performance characteristics. This differentiation derives from
changes in inter- and intra-molecular interactions which define
their supramolecular structure. These differences are enacted via
changes in composition, ionic gradients, drawing speed, and drying
conditions of released silk [48]. Likewise, silk-based composite
mechanical properties can be tuned via chemical and non-
chemical modification of silk microstructure.
One common problem for reconstituted silk fibroin is poor
control over crystal confinement and composition. Methanol-
annealing, shearing, heating, and many more methods can
facilitate a full transition from silk I to silk II within a few minutes,
but the degree of crystallinity is difficult to control [393–395].
Hydrogen bonds form quickly within silk molecules, leaving little
time for reorientation into directions for maximized strength
[395]. Resulting silk structures have high moduli but exhibit brittle
fracture. Poor control over crystallinity also effects degradation
kinetics because increased crystallinity lengthens degradation
time. Hu et al. showed that the thermal water vapor annealing
method enables better control over degree of crystallinity and
degradation kinetics [375]. The study provided a discrete outline of
which temperatures to use in this process to achieve specific
degrees of crystallinity, degradation rate, and toughness.
Similar results were achieved by introducing plasticizer
glycerol to silk films. Glycerol impede some intra- and intermo-
lecular silk-silk interactions, while facilitating others. This results
in change from silk I to disordered silk II structures, where
heterogeneity and dispersion of beta sheets allows for retained
flexibility. Glycerol infused films exhibited comparable crystallini-
ty to water and methanol annealed silk films after removal of
glycerol and with ductility 21 times greater than water annealed
samples [396].
Di-tyrosine crosslinking is a chemical alternative to non-
chemical modification of hydrogen bonding. Most notably
horseradish peroxidase facilitates tyrosine crosslinking of proteins
in the presence of free radicals from hydrogen peroxide. Partlow
et al. have demonstrated the utility of HRP crosslinking in tuning
elastomeric properties of silk hydrogels that are also fully
degradable thanks to their all-natural constituents [397]. Resulting
systems have the elastic modulus up to 10 kPa and Exhibit 100%
strain rarely seen in silk-based hydrogels. Even hydrogen peroxide
alone can induce a silk I–silk II shift comparable to methanol by
redox driven disulfide crosslinking of cysteines on silk-elastin-like
proteins [398].
Silk has been applied to many biomaterial applications
including as capsules, scaffolds, and films. Beyond meeting
fundamental design criteria, silk has broad applicability in
biomaterial design owed to its multifunctionality [399–401].
Silk-like peptides can also be used to create actuating films. For
instance, Ye et al. constructed LbL films using alternating active silk
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 27

Fig. 21. (a) The fabrication of bimorph silk ionomer films using lithography, reproduced from [399] with permission. Copyright 2016 American Chemical Society; (b) The
effects of dip coated then crystallized silk films on strawberry preservation, reproduced from [401] with permission. Copyright Marelli et. al licensed under CC BY 4.0; (c) Silk
microneedle patches for subcutaneous delivery (d), reproduced from [405] with permission. Copyright 2011 John Wiley & Sons.

ionomer and passive crosslinked silk b-sheet layers as shown in
Fig. 21a [399]. After deprotonation, the silk ionomer layer swells,
and the differential stress between the swollen silk ionomer layer
and constant volume crosslinked layer will induce film folding
[399]. This folding effect was also achieved with silk-polymer
composites. In another example, Romera et al. constructed
actuating silk-polypyrrole composites [400], where the polypyr-
role was functionalized onto porous silk fibroin films. Upon
electrical stimulation, polypyrrole releases anions and contracts as
the silk layer expands.
Silk microstructure control also open paths toward preserving
organic matter. To this end, Marelli et al. exerted control over
crystal confinement to produce silk membranes that prevent fruit
degradation [401]. They dip coated various fruits including
bananas and strawberries in aqueous silk fibroin followed by
water annealing for twelve hours to reach 53% beta-sheet content.
Fig. 21b shows pictures of untreated (i and iii) and treated (ii and
iv) at time zero (i and ii) and after seven days (iii and iv). The highly
crystalline protein film impeded permeation of air and preserved
the strawberries for up to a week at room temperature. This
capability is being applied to preservation of enzymes and other
active biological matter.
The tunability of silk makes it adept in this area where selective
degradation determines a drug’s effectiveness and controlled
permittivity ensures activity even after shipping. Silk based
structures are used to stabilize enzymes like HRP and lipase
[402,403]. More recently, silk has proven effective in stabilizing of
complex matter such as blood. Blood contains proteins, lipids,
peptides, enzymes, and metabolites used as biomarkers by
physicians. Kluge et al. used silk matrix encapsulation to preserve
blood through elevated temperatures and freeze-thaw cycles
(Fig. 21c) [404]. These initial results can be considered as a proof of
concept for the future of blood sample transport and preservation.
Silk’s suitability for enzyme entrapment stems from its ease of
functionalization. This property, partnered with facile aqueous
processing, make it possible to design many constructs with drugs
or other functional components loading. Just as silk capsules and
films have been used for enzyme entrapment and release, other
more complex structures can be built using silks. Thanks to
micromolding, drug loaded silk-microcapsules have been designed
to deliver drug innocuously from a microneedle patch (Fig. 21d)
[405].
6.3.2. Biodevices from silk materials
The advantages of silk as a biomaterial carry over into its usage
in bioelectric composites. Although, silk fibroin is not electrically
conductive, it can be integrated into conductive biocomposites by
compounding with electronically active components. If for use in
vivo, degummed silk offers the benefits of low immunogenicity and
controllable biodegradation. For use on spherical or non-uniform
surfaces, silk confers flexibility. This same flexibility partnered
with engineered extensibility make it ideal for use in strain sensors
for skin deformation. In all these areas, silk fibroin forms a
lightweight flexible, extensible, bio-compatible matrix for loading
of electrically active components.
For example, Hu et al. created skin-mounted tactile sensors
using one-pot batch processes to make large-area films. They used
one-pot silk-GO mixture to lay large area, conformal bio-paper and
used electrochemical reduction by aluminum paste to form circuits
(Fig. 22a) [5]. Moistening the metal-GO junction, either by
deionized water or human skin, generates an electrical potential.
The humidity sensing films exhibited fast activation, deactivation,
and recovery rates when cycled with each output of equal and
opposite magnitude. Additionally, the output did vary according to
the magnitude of water molecular and bio-electrolyte ion
presence, suggesting that this could also be used for qualitative
28 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41

Fig. 22. (a) Silk-graphene oxide composite based tactile sensor, reproduced from [5] with permission. Copyright 2016 John Wiley & Sons; (b) Depicts stress and thermal
sensor with silk fibroin substrate for cardiac mapping in animal models, reproduced from [25] with permission. Copyright 2010 Springer Nature; (c) Silk based sensor for
detection of food degradation, reproduced from [28] with permission. Copyright 2012 John Wiley & Sons.

Similar techniques have been applied to for detection across the

analysis of water ionic content. Ma et al. then expedited the process
electromagnetic spectrum.
for creation of similar devices capable of operating as proximity
Optical biological sensing applications not only benefit from the
sensors with large-volume scalable screen printing [191].
previously mentioned substrate characteristics but also from silk’s
Kim et al. constructed similar devices where silk fibroin, not its
capacity for enzyme stabilization [187]. As Domachuk et al. show,
functional filler, was the most prominent component (Fig. 22b)
silk matrices can be readily loaded with optical elements using
[25]. They fabricated transparent, soluble substrates for electrode
lithography [409]. At the same time, they immobilize hemoglobin
arrays from concentrated silk fibroin. Polyimide undergoes
onto the silk film. This creates an oxygen sensor since hemoglobin
photolithography and patterned etching to form wire like planar
is an enzyme used to in the body to oxygenate blood cells. Added
electrode arrays. The high concentration silk fibroin forms a more
structural complexity in the form of microfluidic pathways
gel-like film. This partnered with the thin circuitry design rendered
demonstrate the breadth of conformations and microstructures
films that conformed to a feline brain. The devices successfully
for optical and electrical devices enabled by silk substrates and
mapped neural activity over select electrodes, however half had
matrices. Just as silk can be a passive component, it can also
poor contact with the brain and didn’t produce reliable neural
contribute optical activity. In nature, sericin affords silk cocoons
response data.
their color and protection from electromagnetic radiation. In one
This same technology has even been applied to map deforma-
instance, Muller et al. submerged silk fibroin fibers in PEDOT-S
tion of the heart as it pumps [406]. The main design modification
solution to create electrochemical transistors [410]. Integrating
was use of kirigami in creating the nanowire electrode. The wires
functionality in to silk fibroin itself rather than substrate or matrix
were cut to have curvilinear profiles, introducing added extensi-
functionalization enables the creation of optical and electrically,
bility through effectively longer interconnects. This technique
active textiles.
enhanced the composites’ ability to actively deform with the heart.
Finally, even if silk shares strengths with its fellow fibrous
The device mapped temperature, electrophysical signals, and
proteins like keratin and collagen, key differences between the
strain in animal models. Recent implementations have been used
proteinaceous components define their different properties as
ex vivo in proofs of concept for wearable device platforms. These
outlined in the following section.
include strain sensing temporary tattoos and temperature
mapping films with energy storage capability [407,408].
Silk’s lightweight and dexterity have also found use in optically 6.4. Other fibrous proteins for bionanocomposites
active devices. Tao et al. took advantage of constructs previously
discussed and exchanged electrodes and metal-GO junctions for 6.4.1. Collagen and gelatin
optical or photonic components like dyes or quantum dots [28]. Fibrous proteins have compositions, and therefore require
They printed a gold array on silk substrate. The resulting film different processing conditions and yield different performance
readily conformed to several edible samples: a banana, a slice of characteristics. Although silk has been an area of intense research
cheese, and, as shown in Fig. 22c, an egg. The devices detected focus, here we explore existing literature in three other major
bacterial contamination on solid foods as well as in a glass of milk. classes of fibrous proteins: collagen, gelatin, and keratin. Although,
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 29

Fig. 23. Schematic summarizing the sources, extraction process, and applications of collagen, gelatin, and keratin. Ocular lens is reproduced from Ref. [416]. Copyright 2011
Elsevier; Knee scaffold is reproduced from [417] with permission. Copyright 2015 Springer Nature; flexible film is reproduced from [418] with permission. Copyright 2015
Johns Wiley & Sons.

distinct materials, they share similar sources, extraction methods,
and a broad range of applications as shown in Fig. 23.
Collagen is the main structural protein in human connective
tissue and comprises 90–95% of organic bone matter and accounts
for tensile strength in blood vessels, cartilage, bones, etc. as well as
fibrils and membranes in vivo [411]. Collagen’s primary structure
consists of glycine-x-y triads where x is mostly proline and y is
mostly hydroxyproline. The molecule has 1000 amino acids at
100 kDa molecular weight wound into a triple helix. Alpha chains
may be the same (homotimer) or different (heteotrimer), thus
multiple forms of collagen exist within the animal kingdom.
When secreted into the extracellular matrix, collagen mole-
cules align head to tail in a staggered array, bringing molecule
crosslinking sites into proximity. The sites link by oxidative
amination with age. The age of collagen, i.e. degree of crosslinking,
determines its solubility. Un-crosslinked, fresh collagen is salt-
soluble. Crosslinked collagen is mostly acid soluble with high
crosslinking necessitating proteolysis by pepsin. In research, type 1
collagen is the most frequently used – often harvested from rat
tails or bovine hooves, soaked in salt, dissolved in acid, and then
dialyzed for aqueous processing.
Denaturation of collagen produces gelatin, a structural protein
commonly encountered in the kitchen but has great utility in
biomedical device design due to its high biocompatibility and
ability to promote cell adhesion, differentiation and proliferation
[412]. Fundamental research focuses on the same gelatin sources
prized in the culinary community, predominately bovine and
porcine skin collagen. Of the two, porcine skin is most popular
because it has greater crosslinking and has many glycine and
proline groups, which result in superior modulus, as well as free
hydroxyl groups that enable facile hydrogen bonding with water
[413]. Other factors of consideration when using gelatin are its
sensitivity to environmental conditions like temperature, humidi-
ty, and pH. At room temperature, gelatin forms semi-crystalline
network that is brittle when dry, so plasticizers like glycerol
usually accompany it to inhibit interchain interactions and thereby
improve toughness and flexibility for use in films, fibers, and 3D
structures.
Duration of denaturation and method of extraction are
important factors in resulting gelatin mechanical properties
[412]. Thermal denaturation disassembles and truncates the
tropocollagen structure, leaving much smaller and less ordered,
30 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
water-soluble gelatin molecules. Denaturation decreases the
propensity of triple helices, secondary structure, molecular weight,
and hydrophobicity, while increasing chain polydispersity. These
factors affect mechanical strength and must be tailored for each
targeted application. Depending on the extraction method,
different gelatins may be produced. Extraction from collagen via
acidic and basic treatments yield type A and type B gelatin,
respectively.
Collagen and gelatin are largely used as matrices for tissue
scaffolds [414]. Like silk they are biocompatible and lightweight.
Their proline residues are sites for crosslinking with glycine or
loading with electrically, optically, or biologically active compo-
nents. However, they mostly were used in scaffolds for tissue
regeneration [414]. For flexible electronics, Moreno et al. recently
asserted collagen’s utility in this field [415]. They fabricated
collagen films and e-beam deposited electrodes directly on
collagen, illustrating the hardiness of collagen compared to silk
whose electrodes are fabricated separately then loaded to the film.
Flexible film-based applications using gelatin are less prevalent,
and research suggests this may be due to its brittleness. Plasticizers
like polyethylene glycol help mitigate this issue as showed by
Ahmed et al. [415] They crosslinked gelatin and chitosan, using a
plasticizer to create flexible, biodegradable packaging films. The
abundant presence of aromatic groups in gelatin enable it to serve
as an ultraviolet light barrier. Applications for gelatin and collagen
are limited, and their implementation outside of scaffolds and
capsules are relatively recent compared to silk fibroin. However,
more time could see its range of utility grow to match the research
and application uses of silk fibroin.
6.4.2. Keratin components
As one of the most ubiquitous fibrous proteins in nature, keratin
enables animals to protect themselves from predators, competi-
tion, and environmental hazards. The fibrous protein does this as
aqueous slime, flexible high strength hair follicles, whale baleen
and feathers as well as high toughness nails, horns, and beaks
[416–418]. Like silk and collagen, keratin derives its strength and
dexterity from hierarchical structure and inter-/intra-molecular
crosslinks. Keratin polypeptide chains containing cysteine amino
acids that crosslink upon oxidation and form filamentous matrices
that organize into lamellar and tubular structures that form
compact, porous structures at the macroscale. Varying degrees of
microscale organization and mesoscale compaction and porosity
can yield a wide variety of mechanical properties, readily tailorable
for use higher performance and niche biomedical applications.
Though available from many sources, for research purposes,
keratin is typically extracted from bovine hooves using the general
approach applied to collagen (Fig. 23). Raw hooves are washed
with distilled water, dried and pulverized then defatted via Soxhlet
extraction. Further incubation and dialysis yields pure keratin. No
additional modification is needed for biocompatibility thanks to
keratin’s natural derivation and cell adhesion promoting factors
RGD and LVD in its sequence.
Due to keratin’s high biocompatibility and high strength,
keratin is used broadly in tissue scaffolding applications. However,
keratin as a pure material tends to be brittle and readily degrades
during use, and so is often used as part of a composite to with other
proteins or polysaccharides to add toughness and stability. Another
way to add toughness is through crosslinking. However, cross-
linking is an expensive option that would alter keratin’s inherent
properties and reduce its biocompatibility [419,420]. Introducing a
plasticizer like glycerol may be the simplest fix for brittleness
when flexibility and aqueous permeability are most desired as
shown by Reichl et al. [416] They used keratin films as scaffold for
ocular surface reconstruction. As was the case for collagen and
gelatin, use of keratin outside of scaffolds or matrices for cell
proliferation is limited. More research into methods to manipulate
the mechanical and structural properties of these proteins is
needed.
7. Polynucleotides for bionanocomposites
7.1. Overview of polynucleotides
Polynucleotides have been intensively used as components in
bionanocomposites because of their robust helical structure and
rich presence of available functional groups that enable strong
interactions with other composite components [421]. The human
body uses polynucleotides RNA and DNA to synthesize biomole-
cules, determine their function, and trigger cell death. Polynucleo-
tides also encode a wide range of genetic predispositions such as
for diseases like diabetes and for environmental protection in
melanin production [422]. Structurally, polynucleotides are chains
of nucleotides – RNA is a single polynucleotide, while DNA consists
of a polynucleotide pair wound helically. Each nucleotide has a
nitrogenous base, a five-carbon sugar (ribose for RNA and
deoxyribose for DNA), and at least one phosphate group. In vivo,
the liver produces nucleotides via de novo synthesis from
metabolized carbohydrates and amino acids. In vitro, nucleotides
are produced by modification of protective groups. And, bacterial
gene expression is used for high throughput production.
While structural proteins primarily impart flexibility and
mechanical reinforcement, polynucleotides confer functionality.
Of most interest for in polynucleotides their use in assembling
bionanocomposite materials and organized structures for bio-
chemical sensing and supramolecular assembly [24,423–426].
Polynucleotides allow fast, label-free detection of biochemical
markers. For instance, Wang et al. fabricated such a system, a
laminated composite of highly conductive chemically modified
graphene and self-reducing sulfonic-acid doped polyaniline with
polynucleotide binding probe on the surface [423]. When DNA
hybridizes with the analyte, this perturbs the self-reduction of
polyaniline and signals the analyte’s presence. Tran et al. used
relatively the same construct, modified GO, to make an immuno-
sensor for microRNA [187]. Similar DNA hybridization based
sensing platforms have been made using gold, ruthenium and
other metals as redox indicators of target hybridization with
binding probes of various levels of specificity. Polynucleotides have
available hydroxyl amine moieties that allow easy silane mediated
surface functionalization.
7.2. Soft nanostructures: DNA origami
Polynucleotides such as DNA have been explored extensively
for their conformation into custom geometries through directed
self-assembly processes. For complex hierarchical nanostructures,
lithographic techniques are currently used, however, difficulty
inducing precisely-directed self-assembly has limited bottom-up
scalability [427]. One way of overcoming this challenge is DNA-
mediated controlled assemblies into these well-defined architec-
tures which are spontaneously created will be precisely duplicated
into composite 3D structures in large quantity.
Sophisticated DNA nanotechnology demonstrated various
designs including 2D and 3D crystals [428,429], nanoscale shapes
[430,431], and nanoscale devices [432,433]. In this technique, pre-
designed cocktails of polynucleotide sequences can self-assemble
and fold in a self-controlled manner under controlled temperature
and chemical conditions to form desired 2D and 3D nanostructures
in a practice known as DNA origami (Fig. 24). This DNA origami
process leverages the highly specific hybridization between
complementary polynucleotide sequences, increasingly available
polynucleotide sequences either synthesized or extracted (i.e. from
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
Fig. 24. DNA origami to creat various nanoscale structures. Reproduced from [430] with permission. Copyright 2006 Springer Nature.
the M13 phage), and increasingly powerful computation suites
such as caDNAno to design complex polynucleotide structures
[434]. Both predictable and programmable, DNA can serve as a
scaffold or frame to enable the construction of 1D–3D structures of
varying complexity. For example, Jorgenson et al. successfully
induced microscale assembly of DNA into rigid L, T, and Y shapes
[425].
Directed assembly can be used to enable assembly of gold and
silver particles as well as other optically active materials into
complex superlattices to form metamaterials by using comple-
mentary interactions and spatial frame of templated DNA
constructs. Young et al. [435] employed similar self-assembly
properties in DNA to construct silver and bimetallic gold and silver
superlattices.
Initially, the authors identified proper constructs with poten-
tially interesting optical activity using electrodynamic modeling,
which predicted the selected structures would exhibit epsilon-
near zero behavior and some optically metallic response. To build
this structure, Young et al. relied on the helical structure of DNA to
orient the chirality of noble metal nanospheres to form liquid
crystal metamaterials then dried to form dense thin films. The
ultimate film exhibited a metallic glossy facade and dielectric
properties as predicted by electrodynamic simulations. This
approach highlights another benefit of DNA-mediated assembly
for optical materials which is that the reliability of DNA induced
assembly enables achievement of results that are a near match
with theory and allows one to precisely nail down specific
compositions and organization with unique functions not achiev-
able in trial-and-error approaches.
Just as DNA-templated nanostructures can be used to manipu-
late visible light, some have used it to manipulate fluorescence.
Typically, detection of biomolecules is limited to tags with distinct
colors in the visible range. However, DNA enables fabrication of
angstrom-sized tags with tunable brightness and color, meta-
fluorophores [436]. This enables better biomolecule detection as
well as a potential disrupter of geometric barcoding since the DNA
assembled metafluorphores can form dynamic intensity-based
barcodes whose color and brightness can be tuned by specific
biomolecular triggers.
Beyond aiding in assembly of optically active nanomaterials,
DNA assembly can also be used to construct complex nano-
electronic “devices” by templating 2D and 3D nanocircuits. Early
31
experiments relied on DNA as a framework to which conductive
metal nanoparticles were loaded[437,438]. Recent experiments
have begun to pave the way towards using DNA backbones as
nanowires without additional modification and biometallization.
Initially, understanding the conductivity of DNA molecules was
compromised by its polyelectrolytic behavior. However, after
significant efforts, it has been demonstrated that the helical, tube-
like structure of DNA could serve as a channel for long-range
charge transfer on long distances with both transfer of vacancies
and electrons demonstrated for helical DNA nanowires.
Building upon this, Magro et al. created a mechanism to trigger
DNA electrical conductivity [439]. In this work, they immobilized
DNA using surface active maghemite nanoparticles (SAMN) and
formed nanobioconjugates that could self-assembled into 1D–3D
structures. When in solution, DNA demonstrated electric conduc-
tion between electroactive solute and SAMN. The opposite was
achieved with free DNA, indicating that triggering by the nano-
particles was necessary for electrical conduction through DNA.
Further investigation of this phenomena at the mesoscale using 3D
structures to form metamaterials exhibited electrical conductivity
comparable to carbon paste (0.013–0.014 S/cm) and durability as it
withstood cycles of voltammetry without losing performance.
Though a long way from forming a device, works like this enable
broader utilization of DNA in bioelectronics and more develop-
ment of more sensitive biosensors. These works provide better
understanding of transport behavior of DNA backbones which is
useful for DNA nanowires and DNA-templated biometallized 3D
nanocircuits.
7.3. Sensing applications of bionanocmposites
One of the areas that has extensively employed polynucleotides
as a component is the field of plasmonic nanosensors for
colorimetric detection of specific biomolecular events. As men-
tioned earlier, LSPR can be excited in metallic nanostructures that
are far smaller than the wavelength of light. The spectral feature of
the far-field radiation from these plasmonic nanoantennae are very
sensitive to the resonant conditions, such as local refractive index
changes, and coupling between individual plasmonically active
structures [440]. Such a peculiar property makes these structures
strong candidates for nanoscale molecular sensors [441]. However,
the electrical field decays exponentially from the surface of the
32 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
metal, meaning the effective sensing radius and coupling distance
of plasmonic nanostructures is in the range of tens of nanometers.
Thus, precise nanoscale positioning of active nanocomponents is
required.
There is already a plethora of examples reported in the literature
with suggestions of plasmonic nanostructures of remarkable
sophistication and versatility that have been fabricated via DNA
guided assembly [442]. These examples include homogeneous
nanoparticle oligomers with specific geometries such as triangle,
square, and hexagon, heterogenous planet-satellite assemblies of
different nanoparticles, even linear chains of different nano-
particles with individually programmable interparticle spacing
[442]. More complex systems such as 1D–3D plasmonic crystals
with programmable anisotropy, mutual positing, and lattice
constants have also been demonstrated (Fig. 25) [442,443].
An obvious application of these DNA linked plasmonic nano-
structures in sensing would be to use them as detection platforms
for complimentary DNA strands in the so called “plasmonic ruler”
setup with high specificity [444,445]. Specifically, pairs of Au or Ag
nanoparticles are linked into dimers by a flexible single strand DNA
that is complimentary to the target sequence. Once the target DNA
is introduced, it hybridizes to the linker DNA, reducing the
flexibility of the linker, and subsequently extends the inter-particle
spacing of the dimer, causing observable color changes. One can
even investigate the specifics of DNA hybridization dynamics by
continuously monitoring the spectral change of the ruler [446].
This approach can be generalized to the detection of other
molecules via the incorporation of DNA aptamers, which are
specific DNA sequences that are artificially evolved to have
selective affinity towards certain molecular targets such as
adenosine [447].
These DNA strands will preferentially bind to target molecules
upon contact, therefore disrupting the existing nanoparticle
Fig. 25. Shape changing DNA–GNP films are fabricated via LbL deposition using a PDMS gasket, reproduced from [443] with permission. Copyright 2016 Springer Nature.
assembly [448]. Simply put, this is the fundamental underlying
principle for almost all LSPR based colorimetric apta-sensors
[441,449]. The exact structural change can vary by design, common
types include the dissociation of particle matrices [450], particle
pairing [451], aggregation formation [452], and induced particle
growth [453], Similar designs are also applied in photoluminescent
nanosensors where paring between a fluorophore and a quencher
(usually an Au nanoparticle) is used [449]. More complex sensing
scheme utilizes the structure actuation of DNA aptamers to directly
trap molecular analyte into ~nm sized gaps between plasmonic
nanoparticles in order to exploit the strong electrical field between
the couple nanostructure for enhanced Raman or infrared
spectroscopy [454,455].
Of course, the application of the nanostructural actuation
behavior of polynucleotides in nano-sensing is not limited to
optically-based devices [441]. The coil transformation of DNA
aptamers upon target binding has long been used in electrochem-
ical sensing of molecular analytes, in which the distance between a
redox center and the electrode surface is modulated by the binding
event [456]. DNA/RNA based aptamers are also frequently used in
field effect transistor based and microcantilever based nano-
sensors purely for their molecular recognition capabilities
[457,458]. The relative small size and chemical resistance of
polynucleotides compared to protein based antibodies help solve
many engineering problems faced by these devices such as sensing
surface regeneration and environmental tolerances.
8. Carbonized bioderived materials
Carbon materials are some of most essential materials for
electronic devices and various other functional applications such
as catalysis, optical devices, and pollutant remediation. Specially,
carbon nanomaterials derived from natural biopolymer are
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41 33

drawing increasing attention due to their low-cost, renewability,
and ease of modification. To transform biopolymers to carbon
materials, the biosource is degraded to release small molecules
such as H2, CO2, CH4, and C2H4, while collapsing to form aromatic
residual molecules that may stack to form a lamellar phase, and
transforming into a conjugated carbon structure (graphitization)
[459].
Although these bio-derived carbon materials exhibit only
modest electrical conductivity, thermal conductivity, and mechan-
ical performance due to their low degree of crystallization, they
possess impressive specific surface area that can reach 3700 m2/g—
even higher than that of graphenes [460]. This high specific surface
area is attractive for energy storage with supercapacitor and
lithium ion battery. Indeed, Zhu et al. reported CNC derived carbon
can be used as high-performance carbon anode of sodium-ion
batteries, which demonstrated high capacity of 340 mAh/g at
current density of 100 mA/g and good stability with 12% capacity
loss over 400 cycles [461]. Generally, the increase of the
carbonization temperature will improve the graphitic region,
resulting in the higher conductivity [462]. However, the high cost
of energy consumption and equipment make this approach not
very cost-efficient.
To solve this problem, other highly conductive carbon nano-
materials such as graphenes and CNT components can be added
(see Section 3.1). For example, the carbonization of well-aligned
GO (GO)-CNF hybrid fibers result in highly conductive carbon
fibers with conductivity of 649T60 S/cm, 20 times higher than
that of carbonized CNF fibers. Moreover, the addition of other
components into the biopolymer or the variation of the carbonized
environment can be used to prepare various element doped
carbon. Heteroatom-doped (P, N-P, B-P) three-dimensional (3D)
nanostructured carbon materials are successfully fabricated by
carbonizing bacterial cellulose pre-immersed in various aqueous
solutions (H3PO4, NH4H2PO4, and H3BO3/H3PO4) respectively,
exhibiting good supercapacitor performance [463]. Luo et al.
[464] reported that the nitrogen-doped (N-doped) carbon can be
prepared by the carbonization of cellulose paper under NH3
environment, which showed a large surface area up to 1973 m2/g.
For biopolymers containing nitrogen groups such as proteins,
direct carbonization without any other component or treating gas
change will lead to the N-doped carbon [465].
Another favorable property of carbonized biopolymer is that
the micro/nanostructure of biopolymer materials can be to some
extent replicated into the carbon materials, which will benefit
various multifunctional applications. For example, chiral nematic
mesoporous carbon can be derived from helical LC structure of CNC
film; highly porous, flexible, lightweight and compressive carbon
aerogel can be derived from bacterial cellulose aerogel for water
purification; stretchable carbon film can be fabricated from the
commercial silk fabrics for wearable strain sensors [466,467].
Active carbon with anisotropic microchannels can be derived from
natural wood [468]; carbon nanomaterials with fibrous stipes can
be obtained from the natural mushroom for solar steam-
generation devices [469].
9. Conclusions, trends, and perspectives
In this review, we highlighted recent research progress in the
structural design, fabrication, and applications of nanocomposite
materials derived from natural biopolymer components by

Fig. 26. Outlook of bionanocomposites. (a) 3D printing of bacteria for producing living cellulose bionanocomposites, reproduced from [470] with permission, Copyright 2017
Schaffner et. al licensed under CC BY 4.0. (b) Mechanically-robust nanostructure of nacre, reproduced from [472] with permission, Copyright 2010 Springer Nature. (c)
Structural color of butterfly, reproduced from [476] with permission. Copyright 2017 American Chemical Society. (d) Conductive structure in electric eel, reproduced from
[479] with permission. Copyright 2017 Springer Nature. (e) Programming DNA nanotechnology, reproduced from [481] with permission. Copyright 2017 Springer Nature.
34 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
focusing mainly on the two most popular representatives, nano-
cellulose and silk fibroins. Because of their abundant functional
groups, multi-leveled organized, and easily reconfigured second-
ary structure, biopolymers can produce complementary interfaces
with various synthetic components with tailored functionalities.
As a result, the combination of biopolymers and synthetic
components usually demonstrates advantages in structural
enhancement and high-performance multi-functionalities. For
example, controlling molecular and supramolecular organization
of biopolymers on graphene surfaces allows efficient load transfer
at synthetic and biological interface, facilitating the construction of
flexible wearable electronic biodevices with enhanced strength
and robustness. Furthermore, incorporation with other synthetic
functional components, such as metallic nanoparticles, adds new
physical and chemical properties of interest such as high electrical
conductivity, barrier transport, catalytic ability, and optical activity
for prospective applications in sensing, energy harvesting and
storage, biomedicine and structural nanomaterials.
Although the last few decades have seen impressive progress in
the applications of naturally derived nanocomposites, several
urgent challenges need great efforts to be addressed. Nano-
cellulose, spider silk, and DNA components still lack efficient
methods of extraction, synthesis, purification, and modification
that are low-cost, scalable, reproducible, and can generate highly
purified components with low polydispersity in dimensions and
composition. For example, current conventional synthesis meth-
ods of nanocellulose materials, including sulfuric acid hydrolysis
and mechanical exfoliation, not only are usually inefficient and lack
dimension control, but involve high energy consumption, hazard-
ous constituents, and capital-intensive manufacturing equipment.
On the other hand, spider silks demonstrate superior perfor-
mance and their structural properties are much higher than those
known for synthetic polymer fibers, but harvesting spider silk
microfibers in sizeable quantities is highly challenging because it
must be drawn from individual spiders in small quantities.
Building a large “spider factory” or other exotic approaches
suggested seem to be a questionable technology prospective and
other alternative approaches should be invented and proven.
Although biopolymer costs of extraction and synthesis have going
down, current costs are still prohibitively high. We believe there
will be persistant gap in materials that are industrially-scalable
and can be assembled into complex architectures within the next
several years. However, some emerging advanced extraction
nanotechniques, such as the enzymolysis and gene engineering,
demonstrate great potential for future large-scale and “green”
production.
Additionally, many naturally-derived polymers cannot be
readily derived from its source, or suffer reduced performance
(e.g., strength) after extraction, a more interesting alternative
approach to address the above issue is recombinant cells within
the composite generating bio-derived composite components. We
believe that the incorporation of recombinant organisms into
composites could generate living bionanocomposites whereby the
bio-derived component is constantly fixed and recycled by biota
within the material, rather than applied one-time in generation
(Fig. 26a). [470] Examples of such systems in nature include bone
or skin, where embedded cells fix and regenerate the material to
retain the organ’s functionality after wear and damage. Living
bionanocomposites could respond to internally programmed
scripts, or external signals, and readjust strength and properties
accordingly which is next to impossible to achieve in current
materials designs. In the very distant future one can imagine an
array of designed synthetic cells pre-programmed to integrate
themselves into biological environment and start generating
tailored biosynthetic components in order to create organized
self-grown materials with fully integrated biological and synthetic
functions.
Despite the aforementioned advantages of bio-derived poly-
mers for structural and functional applications, current applica-
tions of these materials usually rely heavily on the properties of
added synthetic components, rather than nanostructure design
alone. Although most isolated biocomponents are relatively
modest in mechanical robustness (compared with inorganic
nanofillers discussed in this review) and non-active in terms of
optical and electrical applications, their hierarchical nanostruc-
tures might provide unique added functionalities. However, these
abilities are rarely realized in current materials designs, let alone
living designs close to the complex hierarchical biomachines
exploited by nature. To this end, a new level of computational
simulations of near-exact replicas of natural and synthetic
components in realistic environments at multi-length and real-
time scales is needed for guiding design efforts. These computa-
tional approaches should be integrated into research efforts to
understand the complex network of interfacial interactions in
order to initiate targeted materials design instead of trail-and-
error approached widely exploited now [470].
The transformation of starting materials into functional
products has traditionally involved bottom-up and top-down
processing. For instance, biocomponents in LbL nanocomposites
build together a network of weak intermolecular bonds to produce
materials with exceptional strength and toughness; whereas
complex set of top-down lithographic processes can transform
polymer resists (including silks and celluloses) into well-defined
high-precision nanostructures. However, each approach is plagued
by current material and processing limitations. Bottom-up
material designs lack defined control over micro- and nanoscale
structure, while top-down approaches are prohibitively expensive
to generate massive structures on a per-unit basis unless at large
economies of scale. Functional and hierarchical nanomaterials
based on bio-derived polymers and complementary nanoscale
components present an unprecedented opportunity to circumvent
these traditional tradeoffs between top-down and bottom-up
approaches. Natural materials such as proteins and genetic
components are created with incredibly high precision, and with
low polydispersity. By using these bio-derived polymers as a
template for use alongside highly-specific reactions (i.e. click
chemistries, Diels-Alder, living polymerizations) would result in a
plethora of new bioenabled nanomaterials that can be solution-
scalable like bottom-up processing, while retaining the specificity
of top-down processing.
As the per weight cost of bottom-up assembled polynucleotides
and polypeptides goes down, these materials can be incorporated
en masse into a new class of active bionanocomposite whereby the
bio-derived component no longer just plays a passive role as a
matrix or is used for structural support. Although errors may arise
in the folding of bioconstructs in the composite, a large number of
such constructs will ensure that a sufficient number in close
proximity retain the functionality to serve the prescribed
application. Also, progress in organic chemistry is likely to yield
a diverse range of polynucleotide derivatives that can perform
various complex tasks at the molecular level, such as highly
selective molecular recognition and catalysis. Integration of these
new functional units into the previously mentioned hierarchical
structures will lead to a whole new generation of bio-nano-
composites. This kind of nanoconstructs will be able to perform
exceptionally sophisticated functions such as nanoscale optical
signal processing in nanophotonic circuits, coherent light genera-
tion and conversion, high speed biocomputing, in vivo multi-
molecular monitoring, and precise cell-targeted therapeutics that
never thought possible before.
 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
The mechanical performance of current generation of biona-
nocomposites is still unsatisfactory when compared with all-
natural materials themselves in many important aspects. Although
the reported bionanocomposite materials show advantages in
some specific properties (e.g. high modulus or strength), the global
performance in terms of a combination of all aspects still is far
below the best natural materials because well-developed multi-
scale structural hierarchy usually miss in man-made nano-
materials Fig. 26b. [472] For example, even if the best bionano-
composites with silks and nanocellulose show excellent toughness
far exceeding synthetic composites, the spider silk by itself still
shows a much more superior toughness and strength reaching
180 MJ m—3 and 1.5 GPa respectively [471]. The careful selection of
biocomponents and synthetic counterparts, as well as the
approaches for their efficient assembly into nanocomposites,
plays a crucial important role for realizing a myriad of structural
applications. To construct highly mechanically robust materials,
we foresee the combination of 1D biopolymers and 2D nanoplates
as choice materials because of their synergistic reinforcement
mechanisms such as sliding and re-orientation of constituent
components. On the other hand, the gamut of different fabrication
methods should be developed and refined to be available for the
reproducible production of bionanocomposites offer advantages
such as the low-cost, environmentally-friendly, potential for high
volume scale-up, and ease of reproduction.
In terms of optical functionalities, current bionanocomposites
basically only demonstrate existing intrinsic optical properties of
each components, such as the transparency of nanocellulose,
chirality of proteins and DNA molecules, and photonics, absorp-
tion, or light emission of nanostructures. Very few examples with
beyond optical properties have been explored. In sharp contrast,
many plants and animals can generate vivid and bright structural
colors via regulating the light scattering and reflection by “using”
the highly periodic photonic nanostructures organized in a tedious
fashion on a large spatial scale [472,473]. For example, Pollia
condensate fruits demonstrate a strong iridescence, caused by
Bragg reflection of large-scale helicoidally stacked CNC multilayers
in the cell walls of the epicarp [472]. The unique changing color at
different viewing angles, a phenomenon known as iridescence, of
the butterfly wing and the metallic beetle skins are suggested to be
generated by the constructive interference arising from the
complex 3D organization of porous and oriented elements
Fig. 26c [474,475,476]. We believe that patterning and constructing
bionanocomposites, using these patterning techniques we dis-
cussed in Section 4.5 (e.g. lithography and 3D printing), to mimic
these unique structures of plants and animals will open the route
toward new forms of optical materials for active biophotonics and
lasing.
Progress towards the integration of conductive bionanocom-
ponents into bioelectronic materials and devices requires a
significant portion of conductive components such as carbon
nanomaterials and metal nanoparticles, usually limiting the
mechanical compliance, flexibility and biocompatability. Interest-
ingly, some animals, like the electric eel, are able to harness the
chemical energy available inside biological systems to output
ultrahigh power with peak potential differences of 600 V and
currents of 1 A [476]. In their specialized electric organs, thousands
of membranes with highly selective and actuating ion channels are
highly packed, allowing electricity generation from the ion flux
that is induced by the ionic gradients Fig. 26d [476]. This concept is
very attractive for the construction of soft biopower sources and
can be potentially realized using the LbL techniques.
Some other reconfigurable and adaptable functionalities that
are a response to the mild changes in the surrounding also are
achievable for bionanocomposites with special structure designs.
For example, the pine cones can switch their shapes responding to
35
the environmental humidity thus creating either highly open or
closed macroscopic shapes. The organized structural elements in
spider legs can detect the position of prey trapped on the silk web
from a complex strain pattern. Peculiar morphology hair on
different legs of wharf roaches initiates fast water propagation
along the legs against gravity driven by unidirectional capillary
forces. However, these unique abilities are rarely replicated outside
of laboratory settings due to a lack of a critical understanding of the
structural origins behind these properties, and of how to exploit
existing biological pathways toward generating these structures.
Naturally occurring phenomena (and only few of them are
mentioned above) show that nature still is a rich source of
engineering inspiration to draw upon in the design and
manufacturing of next generation bionanocomposite materials.
While some progress has been made toward understanding vivid
bionanocomposites with tunable structural color caused by
responsive layered structures with periodic refractive index
variation, the intimate combination of structural and functional
purposes observed in the natural materials is still largely
unexplored for current materials designs.
In previous sections of this review, we have shown the
seemingly infinite applications of nanocellulose and silks as
structural, encapsulating, and functional materials. However, in
each case, only micron scale proofs of concept usually exist. The
same is true for DNA constructs, which mostly serve as a binder for
biological sensors and structural template. Due to the highly
specific pairing of nucleobases, DNA and RNA strands can assemble
in an efficient and predictable manner, even in complex chemical
environments. Not surprisingly, such properties are considered
extremely attractive in the field of nano-fabrication, as different
nanocomponents can be easily functionalized via conjugation
chemistry and spontaneously assemble into desired superstruc-
tures that are otherwise very difficult, if not impossible, to
manufacture using traditionally top-down microfabrication tech-
niques Fig. 26e [477,481].
It is worth to note that although DNA nanotechnology is
currently entering the fourth decade since its inception by Seeman
[478], progress in DNA-guided assembly of such composites has
been limited by the availability, design, and knowledge over
control in DNA linker strands. Advancements in this field has only
accelerated after key innovations such as the establishment of
robust DNA-nanoparticle systems in spherical DNA nanoparticles
[21], new design themes of folding bio-derived scaffold strands
[430], and ever-decreasing costs of synthetic DNA as a source
material for large-scale development [479]. However, while
polynucleotides remain the premier polymer for the precise
localization of attachments and folding to form composite
structures—the barriers to source material cost is still one of the
major factors limiting their use as an engineering material. In the
short-term, we expect research interest in polynucleotide-guided
assembly to focus on applications that require high-precision and
low-scale. As the cost of polynucleotides and the cost of the design
of their structures continues to decrease, we expect to see the first
practical applications of polynucleotide-based nanocomposites in
some unique cases initially.
Utilization of DNA as self-assembled 3D templates opens a
route toward design of highly specific nanostructures through co-
and self-assembly processes such as DNA origami. But we believe
that this is only the first class of bio-derived molecules that can
leverage multistage folding by-design. Such pre-programmed
folding processes will be replicated as protein origami, whereby
we expect synthetic control over protein primary sequence,
assembly environment, and controlled introduction of synthetic
co-factors and co-enzymes could create even more versatile
structures and machinery than what we see today accessible with
DNA.
36 R. Xiong et al. / Materials Science and Engineering R 125 (2018) 1–41
The dual function of polynucleotides as both a molecular
recognition unit and a programmable structural scaffold/template
is a unique advantage that will likely continue to yield exciting
results in the field of nano-sensing. As advanced DNA technologies
such as extended genetic alphabet based aptamers and gigadalton-
scale brick-based assembly mature [480,481], significantly more
complex nanomachinery can be envisioned. Such nanomachines
will not only be vastly superior to existing DNA based nano-sensors
in terms of sensitivity, selectivity, and dynamic range, but might
also enable entirely new branch of functions such as stimuli
triggered orthogonal molecular responses. Also, progress in
organic chemistry is likely to yield a diverse range of polynucleo-
tide derivatives that can perform various complex tasks at the
molecular level, such as highly selective molecular recognition and
catalysis. Integration of these new functional units into known
hierarchical structures will lead to a whole new generation of bio-
nanocomposites. This kind of nanomaterials will be able to
perform exceptionally sophisticated functions that have never
being thought possible before.
Overall, thinking about far reaching efforts in future endeavors
relevant to the topic of this review for finding solution of solutions
to the biggest issues of our time we can suggest that providing
healthcare to world’s large ageing population remotely, enabling
preservation of food over longer periods to address food insecurity,
and creating more dynamic/protective human-surrounding inter-
faces are most relevant grand challenges to think about. Many
other advanced bionanocomposites based upon bio-derived
components, including nanocellulose, silks, and DNA discussed
in this review can play a role in addressing these challenges in near
future as sophisticated structural elements, protective clothing,
embedded sensing skins, self-diagnostic skins, self-powered
implants, actuators and sensors, self-navigating gene/drug deliv-
ery nanopills, enhanced vision lenses and hearing assisting
implants, or self-healing bones and skeletons, to name a few.
Acknowledgments
The research in this field is supported by the National Science
FoundationDMR 1505234, CBET-1401720, CBET-1402712, and
IMMI-1538215 Grants (interfacial assemblies, biosensing, and
nanocomposite fabrication), the U.S. Department of Energy, Office
of Basic Energy Sciences, Division of Materials Sciences and
Engineering Award # DE-FG02-09ER46604 (plasmonic nano-
structures), Air Force Office of Scientific Research Award FA9550-
14-1-0269 Award and 238-5404-GITAzimuth-AFRL Grant
(biointerfaces and bionanocomposites).
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