International Journal of Biological Macromolecules 127 (2019) 606–617

Contents lists available at ScienceDirect

International Journal of Biological Macromolecules

journal homepage: http://www.elsevier.com/locate/ijbiomac

Review

Cellulose/calcium phosphate hybrids: New materials for biomedical and

environmental applications
Ahmed Salama
Cellulose and Paper Department, National Research Centre, 33 El-Bohouth st., Dokki, P.O. 12622, Giza, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: The use of cellulose as an alternative to synthetic polymers might permit the decrease of environmental impacts
Received 16 November 2018 by achieving more easily biodegradable or reusable materials. Recently, cellulose and inorganics are synergisti-
Received in revised form 23 January 2019 cally coupled to tailor promising functional hybrids with unique properties. The current review presents an over-
Accepted 23 January 2019
view of the recent trials for preparing cellulose/calcium phosphate hybrid materials and offers prospects for
Available online 25 January 2019
many new applications in diverse fields. During the whole review, different cellulose forms and cellulose deriv-
Keywords:
atives are being explored as fillers or templates for the design of new functional materials and support for the
Cellulose loading of different calcium phosphate phases. The functionalization of cellulose with calcium phosphate was
Hybrid carried out to construct new and attractive physicochemical properties that are being exploited for different ap-
Calcium phosphate plications such as bone regeneration, drug delivery vehicles, dental repair and adsorption. The studying of cellu-
Biomineralization lose/calcium phosphate hybrid materials is supported by increasing concern in providing smart materials that
combine best of the calcium phosphate properties along with cellulose. The review also aims to study the driving
forces and limitations towards structuring of cellulose/calcium phosphate hybrid materials. It appears that the
use of cellulosic materials for constructing new hybrids is very promising for biomedical and environmental
applications.
© 2019 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
2. Cellulose structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
3. Hybrid materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
4. Calcium phosphate phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
5. Applications of cellulose/calcium phosphate hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
5.1. Bone grafting and regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
5.2. Drug delivery applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
5.3. Adsorption of heavy metals and dyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
6. Cellulose forms widely used in calcium phosphate-based materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
6.1. Microcrystalline cellulose/calcium phosphate hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
6.2. Cellulose nanomaterials/calcium phosphate hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
6.3. Bacterial cellulose/calcium phosphate hybrid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 611
6.4. Cellulose derivatives/calcium phosphate hybrid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612
6.4.1. CMC/calcium phosphate hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612
6.4.2. Other cellulose derivatives/calcium phosphate hybrids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
7. Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615

E-mail address: Ahmed_nigm78@yahoo.com.

https://doi.org/10.1016/j.ijbiomac.2019.01.130
0141-8130/© 2019 Elsevier B.V. All rights reserved.
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
1. Introduction
Organic/inorganic hybrid materials have gained great interest for
biomedical and environmental applications due to their exciting chem-
ical, physical, and biological properties [1–3]. Polysaccharides have re-
cently developed as sustainable polymers for preparing various hybrid
materials in biomedical applications [4–9]. Polysaccharides are exten-
sively investigated in biomedical applications owing to their remarkable
physicochemical properties, abundance, structure diversity and low
cost. Chemically, polysaccharides may be composed of a single kind of
monosaccharides or two or more different monomeric units and can ac-
quire positive or negative charges through functionalization. The
charged groups are useful for building networks, increasing the bioac-
tivity and to adsorb different organic and inorganic species [10,11].
This review will report about the trials for using cellulose, in different
forms, and its derivatives in calcium phosphate mineralization. The re-
view will also include a brief account about definition of the terms hy-
brid and calcium phosphate mineralization with various examples of
these hybrids, which represented ever-increasing interest in the past
few years.
2. Cellulose structure
Cellulose is a naturally occurring, renewable, biodegradable and bio-
compatible polymer. Soft and hard wood from higher plants, certain
bacteria, fungi and several marine animals are the most exploited
sources of cellulose [5,12]. There are several polymorphs of crystalline
cellulose (I, II, IIII, IIIII, IVI, and IVII) with cellulose I and II being the dom-
inant crystalline forms [5]. Cellulose I, crystalline cellulose, is naturally
produced by variety of organisms (trees, plants, tunicates, algae, and
bacteria). Its structure is thermodynamically metastable and can be
converted to either cellulose II or III. Cellulose II, with monoclinic struc-
ture, has the most stable structure and can be produced by either regen-
eration or mercerization [13]. Cellulose III can be formed from cellulose I
or II through liquid ammonia treatments, and subsequent thermal treat-
ments can then be used to form cellulose IV. Cellulose is a long-chain,
high molecular weight homopolymer composed of dimers or disaccha-
rides from D-anhydroglucopyranose units (AGU) joined together via β-
1,4-glycosidic bonds [13] and every other monomer is rotated 180° with
respect to its neighboring unit. The degree of polymerization (DP) varies
from few hundred to 20,000 AGU unit depending on the source and ex-
traction technique [14]. The intermolecular and intramolecular hydro-
gen bonds not only provide cellulose with excellent mechanical
properties but also render it insoluble in most solvents [12]. The reactiv-
ity of the three hydroxyl groups at C-2, C-3 and C-6 offers possibilities
for preparing useful derivatives. The properties of the derivatives de-
pend mainly on the type, distribution and uniformity of the substituting
groups. The average number of hydroxyl groups replaced by the substit-
uents is the degree of substitution (DS), the maximum being three.
When side-chain formation is possible, molar substitution (MS) is
used to denote the length of side chain. Properties that are most strongly
affected by DS and MS are the solubility and plasticity. Chemical
modifications of cellulose were performed for increasing cellulose func-
tionality and consequently increasing its bioactivity for inorganic min-
eralization [15,16].
Cellulose and its derivatives can be used as sustainable alternatives
to many synthetic polymers required for many industries. Several ex-
amples of cellulose derivatives which are widely applied in biomedical
and industrial fields include cellulose ethers and cellulose esters such
as carboxymethyl cellulose (CMC), cellulose acetate, hydroxyethyl cel-
lulose and cellulose propionate [17]. Cellulose exhibits unique features,
such as low density (1.5–1.6 g cm−3), bio degradability, high tensile
strength (290–600 MPa for crystalline cellulose), and high Young's
modulus (100–140 GPa for the crystalline region) [17]. However, cellu-
lose suffers from significant drawbacks such as poor solubility in aque-
ous and organic solvents, poor functionality and poor dimensional
607
stability. Research efforts have focused on improving cellulose function-
ality to expand the scope of its use. Hybrid materials made from cellu-
lose and inorganics are promising class of materials which have been
widely applied as composite polymer films, sponges, hydrogels, ion ex-
changers, membranes, dressing shells for encapsulated drugs, etc. These
materials are also very attractive from a sustainability point of view,
since they enable using of renewable resources and reduce the use of
petroleum-based synthetic polymers [16,18].
3. Hybrid materials
Hybrid materials are composites obtained by mixing at least two
components, commonly inorganic and organic materials on the molec-
ular scale. The use of hybrid materials in biomedical formulations is
highly beneficial owing to the combined properties of both the organic
moiety, such as functionality and flexibility, with heat resistance and
stability of the inorganic materials [19,20]. Hybrids can be synthesized
via different approaches: Biomimetic mineralization, sol-gel process,
exchange or grafting. The interaction between the organic and inorganic
parts in the hybrid can be via weak bonds (hydrogen, van der Waal's or
ionic bonds) or strong chemical bonds (covalent or iono-covalent
bonds) [21].
Bio-hybrids such as bones, teeth, and shells exhibit distinct mor-
phologies and created by animals for exact functions such as structural
support, sensing, and toxic waste removal. Preparation of new hybrids
with distinct structure and morphology is very effective for biomaterials
such as bone tissue engineering [22] and encapsulation of hydrophobic
drugs [23]. Moreover, hybrid materials have the merits of organic mate-
rials such as lightness, pliability and functionality besides the heat resis-
tance and the stability of inorganic compounds [20]. Polysaccharides/
inorganic hybrid materials represent generic importance in the formu-
lation of biocompatible microcapsules [24,25]. For example, the incor-
poration of montmorillonite into regenerated cellulose film was
significantly improved thermal stability, mechanical and gas barrier
properties of the cellulose materials [26]. Moreover, the mineralization
in the presence of organic polymers can led to different mineral phases.
Cellulose/CaCO3 hybrid showed that increasing cellulose concentration
was found to favor CaCO3 growth and has an influence on the morphol-
ogies change of CaCO3 from polyhedral to cube [27]. However, poor in-
teraction between the polymer and inorganic represents obstacles that
cannot be entirely ignored.
Biomineralization is the process of in-vivo formation of inorganic
minerals. Recently, mineralization has emerged as a smart technique
for the design of innovative materials and systems [28]. Moreover,
bio-inspired strategies are fascinating tool for constructing wonderful
sophisticated and hierarchical features. Biomimetic hybrid materials
composed of cellulose and calcium phosphate components have
attracted increasing interest in biomaterials [1]. The development of
biomineralization-inspired (bio) materials based on cellulose and its
derivatives is a promising technique. There are many publications on
bioinspired mineralization of calcium phosphate controlled by synthetic
polymers (see refs [1, 22]), the research work on cellulose and its deriv-
atives as interesting candidates for calcium phosphate growth is still
limited.
4. Calcium phosphate phases
Calcium phosphate is the main inorganic constituent of biological
hard tissues such as bone and teeth. It gives organs stability, hardness,
and function. Biologically formed calcium phosphate is often
nanocrystals that are precipitated under mild conditions. Calcium phos-
phate has an excellent biocompatibility and consequently it has found
biomedical applications, particularly for hard-tissue regeneration [29].
It can be prepared in different amorphous and crystalline phases ac-
cording to the preparation conditions. The different phases vary in
their chemical and mechanical properties [22]. In polymer-controlled
608 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
calcium phosphate mineralization, different phases such as amorphous
calcium phosphate (ACP), dicalcium phosphate dihydrate (DCPD,
brushite CaHPO4·2H2O), dicalcium phosphate anhydrous (DCPA,
monetite CaHPO4), hydroxyapatite (HAP, (Ca5(PO4)3OH)),
chloroapatite (ClAP, (Ca5(PO4)3Cl)), floroapatite (FAP, (Ca5(PO4)3F))
were reported [30]. Studying the biomimetic crystallization of calcium
phosphate is crucial to design biocompatible implants and to treat dis-
eases related to mineralization. In the field of calcium phosphate miner-
alization, the details about the transformation pathways into crystalline
materials are not intensely investigated like calcium carbonate [22].
However, few models have been proposed to interpret the calcium
phosphate mineralization and Fig. 1 shows a recent example proposed
the mineralization at the interfaces.
In the field of biologically inspired mineralization process, many ef-
ficient additives are available with complex influence on the mineraliza-
tion reaction. During this review, the outcome of the mineralization
experiments produced from using cellulose or its derivatives as addi-
tives will be discussed.
5. Applications of cellulose/calcium phosphate hybrids
5.1. Bone grafting and regeneration
Bone, the major normal calcification presented in mammals, serves
as structural support for the body and as the reservoir of calcium and
phosphate ions needed for different functions in the body. It is a com-
posite material of biological apatite and type I collagen. The hierarchical
organization of bone has been successfully simulated by HA mineraliza-
tion on amphiphilic peptide nanofibers, collagen and synthetic poly-
mers [1].
Cellulose has been established to be biocompatible polymer for both
granulation tissue and bone regeneration. The presence of hydroxyl
groups facilitates the immobilization of cell adhesive proteins such as fi-
bronectin [32]. Searching for new human-derived bone tissue is re-
quired due to the donor supply shortage and the infection risk.
Therefore, to overcome these problems, the regeneration of bone tissue
using sustainable hybrid materials has developed as a promising tech-
nique in tissue engineering. Hybrid materials designed for bone regen-
eration applications should have distinct properties. These hybrids
must be biocompatible, biodegradable and osteoconductive.
Calcium phosphate hybrids have attracted great interest and recom-
mended for many medical tasks due to their bioactivity, biocompatibil-
ity and the compositional resemblance with the humane bone. HAP and
tricalcium phosphate are the most commonly applied famous phases in
Fig. 1. Model of calcium phosphate nucleation and growth at the air water interface.
Reprinted from Ref. [31] with permission from Springer Nature, copyright 2010.
the preparation of hybrid materials for biomedical applications [33]. The
mineralization of calcium phosphate phases on the artificial implant is
crucial for joining the implant to the natural bone [34]. Biomimetic
strategy is an essential route for the formation of calcium phosphate
on the polymers for developing new polymer based bioactive materials
[35]. Polysaccharides such as cellulose, chitin [36], chitosan [37], algi-
nate [38] or their derivatives are subjected to a solution mimicking the
inorganic ingredients in the human blood plasma, which is generally re-
ferred to simulated body fluid (SBF) for studying the capability of cal-
cium phosphate growth.
5.2. Drug delivery applications
Controlled drug delivery aims to deliver the drug at a predetermined
rate for a specified period of time. Inorganic materials or polymers, or
their combination, were used for preparation of drug delivery systems
such as vesicles, micelles, nanocapsules, nanospheres, microspheres,
microemulsions, films, or hydrogels [39]. The drug release can be by dif-
fusion, degradation, swelling and affinity-based mechanisms [40]. The
most important strategies of controlled release drug systems is the
maintenance of drug level within a desired range and to achieve more
effective therapies. Controlled drug delivery occurs when a drug or an
active substance, embedded within or combined with the excipient, is
released in a predesigned manner, whether constant or cyclic, over a
long period. Polymers are commonly used to modify the drug release
characteristics not usually offered by conventional dosage forms, such
as solutions, ointments etc.… [41].
Polysaccharides/calcium phosphate hybrid materials are interesting
smart materials that can overcome the burst release problems of drugs
from the organic matrices [25]. Hydroxyapatite, the main calcium phos-
phate form in humane natural bone, can be readily resorbed into bone
tissues. Moreover, calcium phosphate has been extensively studied for
medical applications and is characterized by excellent biocompatibility,
bioactivity as well as osteoconductivity.
5.3. Adsorption of heavy metals and dyes
Higher consumption of synthetic dyes and heavy metals for many
industrial applications has led to generating hazardous wastes. Syn-
thetic dyes which commonly used in printing and dyeing industries
are often highly toxic, carcinogenic and mutagenic [42]. Many attempts
have been carried out for preparing cheap and effective adsorbents con-
taining natural polymers to adsorb the toxic dyes from waste water
[43–45].
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
Calcium phosphate is capable to establish bonds with organic mole-
cules of different size. However, the powder form or calcined pellets
form limits its applications. Organic polymer/calcium phosphate hy-
brids materials have been investigated for the removal of environmen-
tal pollutants such as dyes [46–48]. The few trials for using
polysaccharides/calcium phosphate hybrid materials for the removal
of environmental pollutants will be reported during the current review.
6. Cellulose forms widely used in calcium phosphate-based
materials
Various cellulose forms and various cellulose derivatives are widely
used for the construction of different cellulose/inorganic hybrid mate-
rials, especially cellulose/calcium phosphate hybris. Incorporation of
such rigid materials into the cellulose endows it improved mechanical
strength as well as stability in the physiological environment. In this re-
view we will focus on different cellulosic forms such as microfibrillated
cellulose (MFC), cellulose nanomaterials, bacterial cellulose (BC) and
some cellulose derivatives as promising additives for biomimetic cal-
cium phosphate mineralization.
6.1. Microcrystalline cellulose/calcium phosphate hybrids
The abundance, low cost, mechanical robustness and biocompatibil-
ity of cellulose are key advantages for using cellulose as a sustainable
candidate for preparing new hybrid materials. The regeneration of
bone tissues using cellulose based materials is preferred, and has devel-
oped as new technique in tissue engineering [49,50]. Different cellulose
based bioceramics have been accommodated to increase the osteogen-
esis properties of cellulose [51]. Howeover, the low processability of cel-
lulose can be an obstacle for constructing a vital complex structure
through various modern techniques such as 3D-printing method. Cal-
cium phosphate mineralization on microcrystalline cellulose may pro-
duce new hybrids with properties that are required for regeneration
of hard tissues.
Several trials have been carried out for preparing cellulose-based
materials for bone tissue regeneration. For example, 3D pore-structure
composite consisting of cellulose and calcium-deficient-hydroxyapatite
was prepared via an electrohydrodynamic printing process supple-
mented with an ethanol bath. The osteogenic activities of Alkaline phos-
phates level and calcium mineralization experiments suggested fibrous
cellulose/ceramic composite as efficient platform for inducing bone
mineralization [32]. However, low solubility in aqueous media and
low bioactivity arising from low functionality of cellulose hamper the
preparation of real cellulose based hybrid materials. Various research
articles have described the successful mineralization of cellulose with
various calcium phosphate phases. For example, oriented calcium phos-
phates were deposited as amorphous form on the surface orientation of
the nematic ordered cellulose templates [52]. Langmuir-Blodgett
trimethylsilyl cellulose films were treated with HCl vapors for preparing
regenerated multilayers. This film was employed as a template for bio-
mimetic calcium phosphate mineralization after activation with a Ca
(OH)2-suspension prior to the biomimetic mineralization from SBF.
The results showed that a layer of highly carbonated apatite lacking hy-
droxyl ions phase was formed. Moreover, mineralization of carbonated
apatite is enhanced on the regenerated cellulose fabrics activated in Ca
(OH)2-suspension compared to as-prepared cellulose as shown in
Fig. 2 [35]. González et al. tried to activate the three hydroxyl groups
presented in the cellulose backbone via reaction with titanium
isopropoxide as coupling agent. The authors studied the bioactivity of
the three new labile hydroxyl groups originated from the reaction be-
tween cellulose and titanium isopropoxide to initiate the growth of cal-
cium phosphate crystals. The results showed that the coupling agent
increases the number of labile hydroxyl groups which act as active
sites to enhance the combination of calcium and phosphate ions to ini-
tiate hydroxyapatite mineralization [53].
609
Aqueous solutions are the dominant solutions used for calcium
phosphate mineralization. Mineralization of non-soluble cellulose in
aqueous solutions often produces heterogeneous materials with prop-
erties that are not suitable for biomedical applications. The most inade-
quate issue of cellulose is again its limited solubility in aqueous
mineralization media. This restricts the processing and mineralization
efficiencies. The insolubility of cellulose reduces the penetration of the
calcium and phosphate ions and the mineralization process produces
surface or near-surface mineral layers. Ionic liquids (ILs) were emerged
as green solvents for dissolving neat cellulose and efficient reaction
media for the synthesis of new homogenous cellulose/inorganic hybrids
[54–56]. ILs have also been shown to occasionally lead to inorganic ma-
terials that cannot be made via conventional approaches [57–61]. ILs
permit to incorporate inorganics, fillers and metal nanoparticles into
cellulose matrix which open the avenue towards completely new com-
posite materials with a tailored chemical composition. ILs have been
evaluated as convenient strategy for producing real homogenous and
hierarchical cellulose/calcium phosphate hybrids. 1-butyl-3-methyl
imidazolium chloride, IL, was used as a reaction medium to prepare cel-
lulose/calcium phosphate hybrid materials. This trial proved that the re-
action environment controlled the crystal phase of the formed calcium
phosphate. Cellulose/hydroxyapatite, cellulose/chlorapatite, or cellu-
lose/monetite hybrids were precipitated at different reaction condi-
tions. MC3T3-E1 pre-osteoblasts cells proliferated on the hybrids
proposing that the ionic liquid-based process produces valuable mate-
rials for regenerative therapies [2].
In our previous study, 1-butyl-3-methyl imidazolium chloride was
used as common solvent to dissolve cellulose and natural wool. The re-
generated cellulose/wool blend was examined as a sustainable bioactive
material for calcium phosphate growth from SBF solution. The morphol-
ogy of regenerated cellulose/wool blend is homogenous without phase
separation appearance which may be arising from the intermolecular
hydrogen bonding between wool and cellulose, as shown in Fig. 3. How-
ever, the mineralized blend showed fibers-like shape with nanometer
sized ordered aggregates composed of hierarchical nanofibers less
than 300 nm. These fibers exhibit Ca/P ratio 1.57 ± 0.1 which suggest
HAP growth. The results showed also that the uniform crystalline HAP
nanofibers mineralized onto the blend is homogenous. The cytotoxicity
of the mineralized blend exhibited good cytocompatibility, offering the
current material for tissue engineering applications [62].
Another trials have been carried out to increase the functionality and
hence the bioactivity of cellulose via grafting with plant protein. Cellu-
lose grafted with soy protein isolate was studied as new functionalized
cellulose derivative for calcium phosphate mineralization. The authors
found that HAP with a rod-like shape was precipitated. The cytotoxicity
of cellulose/soy protein isolate/calcium phosphate hybrid was evaluated
using animal fibroblast baby hamster kidney cells and the results sug-
gested this material as potentially useful hybrid for tissue engineering
[63]. Moreover, cellulose/soy protein isolate/calcium phosphate hybrid
was reported as efficient adsorbent and promising material for water
purification. This material showed high adsorption capacity for methy-
lene blue removal and the adsorption capacity reached to 454 mg/g.
The adsorption results of the sustainable cellulose grafted SPI/hydroxy-
apatite hybrid material present the current material as a likely adsor-
bent for water treatment [3].
6.2. Cellulose nanomaterials/calcium phosphate hybrids
Microcrystalline cellulose, the structural units in higher plants, con-
tains highly ordered (crystalline) domains alternating with disordered
(amorphous) regions. Cellulose nanomaterials can be isolated from var-
ious lignocellulosic materials such as wood (hardwood and softwood)
and other agriculture residues (bagasse, rice straw, cotton stalk, etc.)
through various techniques including mechanical, chemical and enzy-
matic treatments [5,64].
610 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617

Fig. 2. SEM of regenerated cellulose fabrics activated in Ca(OH)2-suspension: (a) as-prepared, (b) after 3 weeks soaking in 1.5 × SBF. TEM of mineralized calcium phosphate on pretreated
cellulose after 3 weeks soaking in 1.5 × SBF.
Reprinted from Ref. [35] with permission from Elsevier, copyright 2005.

Cellulose nanocrystals (CNCs) were extracted mostly through acid
hydrolysis process using sulfuric acid, hydrochloric acid and phosphoric
acid which cleave the amorphous domains and leaving well-defined
crystalline rods (crystalline regions as shown in Fig. 4) [14].
In the field of hybrid materials, CNCs have received great attention
due to their unique properties such as high surface area of
150–250 m2 g−1, low density, excellent mechanical properties, high as-
pect ratio and high crystalline order and chirality. CNCs were applied as
additives for foods and cosmetics, drug delivery, insulator aerogels,
bone or tooth replacement materials etc. [14,66]. Different hybrid mate-
rials and hydrogels have been constructed based on CNCs [64,67,68]. For
example, the presence of different functional groups onto the CNCs sur-
face has direct impact on the mineralization and growth of HAP from
SBF. The HAP content and the surface area measurements showed that
the sulfonate and phosphonate groups, originate during acid hydrolysis,
significantly contribute in the hydroxyapatite mineralization on the
CNCs particles. The biocompatibility of the CNCs/hydroxyapatite mate-
rials were evaluated by cell viability measurements using fibroblast
cells and the results supported these materials for bone tissue engineer-
ing. CNCs extracted using sulfuric acid/hydroxyapatite hybrid exhibited
an improvement in the cell viability compared with pure HAP [69].
Mai Ishikawa et al. prepared nanosized hybrids through controlled
nucleation and growth of a c-axis-oriented HAP onto CNCs. The authors
reported the formation of transparent thin coatings via evaporation-
induced assembly of CNCs/HAP nanocomposites [70].
Cellulose nanofibers (CNFs) can be prepared from agricultural wastes
using mechanical disintegration methods in combination with enzymatic
or mechanical treatments. Using strong mechanical shearing such as
grinding, and high-pressure homogenization was found to promote the
progressive release of constitutive microfibrils. CNFs have gained increas-
ing attention due to their unique properties such as high surface area,
good strength properties and abundant availability. One of the most im-
portant CNFs is TEMPO-oxidized nanofibrillated cellulose which can be
prepared from (2,2,6,6-tetramethyl-1-piperidinyloxy)-mediated
oxidization (TEMPO) of cellulose followed by mechanical defibrillation
using high-pressure homogenization. Fig. 5 shows TEM images of CNF
and TEMPO-CNF isolated from date palm fruit stalk pulp using Masuko
grinder or high-pressure homogenizer.
TEMPO-oxidized nanofibrillated cellulose was investigated as a sus-
tainable material for preparing injectable hybrid materials for bone re-
generation. The hybrid martial was prepared via incorporation of
biphasic calcium phosphate at a ratio of 50 wt%. Cytotoxicity and alka-
line phosphatase level tests revealed that the TEMPO-oxidized
nanofibrillated cellulose based hybrid has nontoxic effect on
osteoblast-like cells [49]. Abouzeid et al. studied the mineralization of
3D scaffold of TEMPO-oxidized nanofibrillated cellulose/alginate mate-
rials for bone tissue engineering applications, as shown in Fig. 6. The re-
sults showed the growth of hydroxyapatite layer with Ca/P ratio 1.76.
The thermal analysis estimated the hydroxyapatite content and was cal-
culated to be 20.1% [72]. In a recent study, the effect of carboxyl content
in oxidized CNFs on the HAP growth was investigated. The study
showed that the increasing of carboxyl content in the TEMPO-oxidized
nanofibrillated cellulose up to 9.9% enhanced the nucleation of HAP
from SBF solutions [73].

Fig. 3. SEM of cellulose/wool before and after hydroxyapatite mineralization and TEM of cellulose/wool/hydroxyapatite hybrid.
Reprinted from Ref. [62] with permission from Elsevier, copyright 2016.
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617 611

Fig. 4. TEM micrographs of CNC obtained from acacia bark by using solvent extraction (left side) and without solvent extraction (right side).
Reprinted from Ref. [65] with permission from Elsevier, copyright 2017.

6.3. Bacterial cellulose/calcium phosphate hybrid
Bacterial cellulose (BC) can be produced by some microorganisms,
such as Acetobacter xylinum and Gluconacetobacter xylinus [74]. In
comparison to the plant-derived cellulose, bacterial cellulose (BC) has
amazing properties as respects to the crystalline structure, fibrous as-
pect, increase surface reactivity, mechanical resistance, biological fea-
tures, high water holding capacity and high purity [33,75,76]. The
diameter of BC is in a range from approximately 25 to 45 nm. It is also
considered as nanocellulose. As a consequence, BC is preferred for vari-
ous biomedical applications, for example artificial skin, blood vessels
and scaffolds for tissue engineering and wound dressing [77]. BC has
the same plant cellulose structure and exhibits a highly fibrous, and
three-dimensional non-woven network structure. Moreover, it is free
from the other contaminants such as lignin and hemicellulose [78]. BC,
however, is economically unfavorable due to high cost of carbon source
[79]. In the aspect of tissue engineering, the important criteria for tissue
engineering materials include inhibition of infection, acceleration of cal-
cium phosphate mineralization and a template for the synthesis of inor-
ganic materials having controlled morphologies. BC has recently
emerged as promising material with these respects [80]. BC and calcium
phosphate materials have been reported for developing of biomaterials
addressed to the prosthetics domain and artificial bone. Despite the va-
riety of hydroxyl groups presented on the BC surface, these groups are
not reactive to growth the calcium phosphate particles. Different re-
search groups modified the reactivity of individual fibers using various
techniques to enhance their bioactivity towards inorganic mineraliza-
tion [81]. For example, BC/HAP nanocomposites were prepared using
phosphorylated and unphosphorylated BC. After soaking the raw BC
and modified BC in SBF for 14 days, few crystals of HAP were formed
on the surface of BC fibers, when phosphorylation was not performed.
However, phosphorylated BC enhances the growth mineralization of
HAP crystals. The results exhibited that the formed HAP was partially
carbonate substituted, similar to natural bone in structure and crystal
size [82].
There have been some studies for employing BC hydrogel in calcium
phosphate mineralization through biomimetic process in SBF [83]. Dur-
ing the biomimetic mineralization, BC were negatively charged or func-
tionalized via introducing new anionic functional groups or mixing with
anionic polymers. The presence of such acidic groups will initiate the
heterogeneous nucleation and regulate the crystal growth of calcium
phosphate. For example, Hutchens et al. prepared new hybrid material
from BC hydrogel and calcium-deficient hydroxyapatite. BC was incu-
bated in CaCl2 solution followed by Na2HPO4 solution and high apatite

Fig. 5. TEM of CNFs (left) and TEMPO-oxidized CNFs (right) isolated from date palm fruit stalks [71].
Image courtesy of M. Hassan.
612 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617

Fig. 6. Fabrication process for 3D printing scaffolds from TEMPO-oxidized nanofibrillated cellulose/alginate.
Reprinted from Ref. [72] with permission from American Chemical Society, copyright 2018.

content was homogenously precipitated in the hydrogel. SEM images
showed that the mineralized calcium phosphate is uniform spherical
calcium-deficient hydroxyapatite particles contained nanosized crystal-
lites with a lamellar morphology as shown in Fig. 7. The chemical struc-
ture of this composite is similar to natural bone apatite indicating that
BC is a promising template for biomimetic apatite formation [84].
Also, in the field of tissue engineering, the preparation of calcium
phosphate scaffolds was carried out using BC as template. The prepared
scaffolds were heated under high temperature in air to remove the bac-
terial cellulose and mineral phases with different morphologies were
obtained. Varying the calcination temperature and the time period
was found to effect on the porosity and grains dimension of the mineral
scaffolds. The pyrophosphate produced after calcination has porous ar-
chitectures consisting of grains connected on the three spatial directions
as illustrated in Fig. 8. Moreover, the bioactivity and biocompatibility of
the prepared materials have established to be suitable for bone regener-
ation purposes [33].
6.4. Cellulose derivatives/calcium phosphate hybrid
Besides cellulose, cellulose derivatives such as CMC and
hydroxyethyl cellulose are important materials in the field of calcium
phosphate mineralization. Two of the key advantages of cellulose deriv-
atives are their solubility in aqueous solutions and the different proto-
cols available for chemical modification. As a result, many research
groups have evaluated the preparation of cellulose derivatives/calcium
phosphate hybrids.
6.4.1. CMC/calcium phosphate hybrids
Carboxymethyl cellulose (CMC) is one of the most water soluble cel-
lulose derivatives. CMC with a DS ranging from 0.4 to 1.3 has gained
special concern because of its versatile applications in, for example, cos-
metics and adhesives. CMC degrades at low rates in the environment
forming nontoxic intermediate [85]. Moreover, CMC has good packing
ability for insoluble drugs and bioactive materials [86]. The chemical
modifications of CMC can offer additional properties that improve its
overall characteristics. The synthesis of cellulose derivatives containing
dispersed inorganic nanoparticles is expected to add new properties
and hence open new avenues for applications in catalysis, electronics,
sensors, nanocomposites, drug delivery, and food packaging [87].
The presence of carboxyl groups in CMC will initiate the nucleation
of calcium phosphate in analogy with calcium phosphate growth in
collagen-based natural bone tissues. Various cellulose derivatives
which exhibit a higher water solubility in aqueous solutions have
been used as alternatives for preparing calcium phosphate scaffolds.
CMC/HAP hybrids display good osteoconductivity and biodegradability
in different biomedical applications. HAP nanocrystals were drowned
in CMC-based hydrogel matrix for preparing hybrid material. CMC hy-
drogel was dipped in HAP solutions with different concentrations. Al-
though the authors reported a degree of distribution for

Fig. 7. SEM images of BC (a) and BC-53%HAP (b) with magnification.

Reprinted from Ref. [84] with permission from Elsevier, copyright 2006.
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617 613

Fig. 8. SEM images of the as prepared composite (A), calcium phosphate obtained after calcining at 800 °C (B) and 1000 °C (C), adapted from ref.
Reprinted from Ref. [33] with permission from Elsevier, copyright 2018.

hydroxyapatite crystals on the surface and inside the hydrogel matrix,
the morphology of this kind of hybrids is far from the structure of the
humane bone. The most real and efficient strategy for preparing hybrid
materials resemble natural bone is biomimetic mineralization tech-
nique [88].
The calcium phosphate nucleation on CMC/silica hybrids was inves-
tigated for biomimetic calcium phosphate mineralization. The authors
suggested that the bioactivity of CMC/silica hybrids is governed by the
CMC content. Although, amorphous calcium phosphate was formed in
the presence of low CMC content, HAP was formed in case of high
CMC content. The compressive modulus and strain at failure of CMC/sil-
ica hybrids increased with the increasing of CMC content up to 15% [89].
Various trials have been carried out to increase the bioactivity of
CMC through various techniques such as grafting with synthetic mono-
mers. Polyacrylic acid (PAA) is an acidic polymer that can absorb the
ions to initiate the mineralization process. PAA was grafted onto CMC
to increase its bioactivity towards inorganic mineralization. CMC-g-
PAA hydrogel was prepared and evaluated as a bioactive hydrogel for
biomimetic calcium phosphate mineralization. After immersing in SBF,
calcium phosphate layers comprised of spherical particles with diame-
ter ~2 mm were formed. The in-vitro assessment displayed that the pre-
pared CMC-g-PAA/calcium phosphate nanocomposite possess pH
sensitivity. The swelling and drug release properties showed that the ef-
fect of mineralization process onto in-vitro bovine serum albumin re-
lease showed pH sensitivity and efficient capability for BSA
encapsulation and delivery [90]. In our previous study, CMC backbone
was grafted with crosslinked polydimethylaminoethyl methacrylate
(CMC-g-PDMAEMA) and then subjected to biomimetic calcium phos-
phate mineralization. The resulted CMC-g-PMAEMA/calcium phosphate
hybrid was investigated as a drug carrier and the results showed signif-
icant efficiency of the formed hybrid to deliver bovine serum albumin
[91]. In another study, CMC-grafted polymethacrylic acid (CMC-g-
PMAA) was prepared by graft copolymerization technique. CMC-g-
PMAA was examined as graft copolymer controlled calcium phosphate
mineralization at different copolymer concentration and pHs. At acidic
conditions, a fiber-like structure consisting of dicalcium phosphate
dihydrate was formed at high graft copolymer content. However,
plate-like structure was formed at low concentration of CMC-g-PMAA.
In basic condition, uniform nanosphere particles with different sizes of
hydroxyapatite were precipitated. CMC-g-PMAA/calcium phosphate
hybrid with bone-like composition could be examined as a bone
grafting material [92]. In our previous study, PMAA/hydroxyapatite hy-
brid was prepared and applied as efficient adsorbent for methylene blue
removal from aqueous solutions. TEM exhibited rods-like appearance of
the mineralized hydroxyapatite with diameter less than 100 nm. The
lattice structure of the crystalline rods showed interplanar spacing
∼0.34 nm and selected area electron diffraction pattern showed
apatite-crystal diffraction features with Arc-shaped and some addi-
tional diffraction spots as shown in Fig. 9. The hybrid material exhibited
adsorption capacity up to 671 mg/g and the adsorption process follow
Pseudo-second- order and Langmuir isotherm models [93].
In another study, CMC/calcium phosphate hybrid sheets were pre-
pared via alternate soaking the disc-shaped CMC sheet in CaCl2/Tris-
HCl (Ca solution) and Na2HPO4 (P solution). The mineralization process
of protonated-CMC sheets produced mineralized sheets with mixed
phase of brushite and hydroxyapatite. The CMC/calcium phosphate
sheet was found to encourage marker gene expressions for later phase
of osteoblast differentiation. Moreover, the mineralized sheets promote
the calcification osteoblast differentiation of human mesenchymal stro-
mal cells [94].
CMC, hydroxyapatite and lysine were used to prepare new mem-
branes either by conventional casting or double decomposition
methods. There is a great difference in the physical and mechanical
properties of the two membranes. Although the membrane produced
from casting method exhibited rough, stiff properties and partially sol-
uble in water, the other membrane exhibited smooth, flexible

Fig. 9. TEM and SAED of CMC-g-PMAA/hydroxyapatite hybrid.

Reprinted from Ref. [93] with permission from Elsevier, copyright 2016.
614 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617

properties and low water solubility. The prepared trifunctional mem-
brane is useful for extracting toxic material bisphenol A (BPA) from
baby food containers. Also it exhibited antimicrobial and antifungal
properties and could be a suitable candidate for use in bone tissue engi-
neering [95].
In the field of drug delivery, cellulose derivatives/calcium phosphate
hybrids were investigated to design a novel simple technique to control
the release rate of the drugs and overcome the repeatedly observed
burst release problems of drugs from organic matrices. CMC/chitosan
polyelectrolyte was prepared and investigated as a sustainable template
for biomimetic calcium phosphate mineralization through different SBF
concentrations. The results showed that different hybrids with different
organic/inorganic ratios exhibited different equilibrium swelling ratios.
The CMC/chitosan/calcium phosphate hybrids attain the equilibrium
swelling after long time. The equilibrium swelling and drug release pro-
file was controlled with increasing the calcium phosphate% in the hy-
brids. The mineralized calcium phosphate crystals could hinder the
permeability of the encapsulated drug and decrease the drug release
profile [96]. Regenerated cellulose acetate (CA) of electrospun mat
was modified with the CMC to increase its carboxylic content and con-
sequently increase its bioactivity for inorganic mineralization. HAP
growth on electrospun fibers was found to be enhanced by the presence

Table 1
Summary of the different cellulose/calcium phosphate hybrids compiled from the literature.

Cellulose form Preparation Calcium and phosphate precursors Ca/P Phase and morphology Applications References
ratio

Microcrystalline Electrohydrodynamic printing Tricalcium phosphate 1.4 Calcium-deficient-HAP Inducing bone [32]
cellulose process mineralization
Microcrystalline Trimethylsilyl derivative of 1.5xSBF 1.55 to Single nano-platelet – [35]
cellulose cellulose 1.62
Microcrystalline Cellulose matrix previously CaCl2 and (NH4)2HPO4 1.75 HAP – [53]
cellulose modified using titanium
isopropoxide
Microcrystalline Using IL as solvent and reaction CaCl2 and K2HPO4 1.3 HAP and ClAP Bone tissue [2]
cellulose medium engineering
Microcrystalline Using IL as solvent and reaction CaCl2 and K2HPO4 0.9 Monetite Bone tissue [2]
cellulose medium engineering
Microcrystalline Cellulose/natural wool enhance HA SBF 1.57 Crystalline HAP nanofibers Bone tissue [62]
cellulose growth engineering
Microcrystalline Cellulose-graft-soy protein isolate SBF 1.6 HAP with a rod-like shape Bone tissue [63]
cellulose engineering
Microcrystalline SBF 1.6 HAP with a rod-like shape Dye removal [3]
cellulose
CNCs CNCs prepared with different acids SBF – HA (different content) Biomaterials [69]
CNCs Simplified SBF – HAP Water-resistant [70]
transparent
coatings
TEMPO-oxidized Mechanical mixing Prepared HA and β-TCP – Biphasic calcium phosphate Bone graft [49]
nanofibrillated
cellulose
TEMPO-oxidized 3D Printing SBF 1.76 HAP – [72]
nanofibrillated
cellulose
TEMPO-oxidized 1.5xSBF 1.54 HAP and β-tricalcium – [73]
nanofibrillated phosphate
cellulose
BC Phosphorylated BC 1.5xSBF Needle-like HA Candidate for tissue [82]
engineering
BC CaCl2 and Na2HPO4 – HAP – [84]
BC Scaffolds calcination Ca(NO3)2·4H2O Pyrophosphate Bone regeneration [33]
(NH4)2HPO4 purposes
CMC CMC hydrogel Prepared HA 1.67 HAP Bone tissue [88]
engineering
CMC CMC/silica hybrids SBF 1.1 to ACP – [89]
1.35
CMC CMC-g-PAA hydrogel SBF 1.53 HAP Drug delivery [90]
CMC CMC-g-PDMAEMA hydrogel SBF 1.53 HAP Drug delivery [91]
CMC CMC-g-PMAA CaCl2*2H2O, K2HPO4 1 to 1.69 HAP and Brushite – [92]
CMC CMC-g-PMAA CaCl2*2H2O, K2HPO4 1.69 HAP Dye removal [93]
CMC Alternate soaking the CMC sheet CaCl2/Tris-HCl and Na2HPO4 – Brushite with a small [94]
amount of HAP
CMC Calcium phosphate/carboxymethyl HAP – HAP Extracting toxic [95]
cellulose/lysine composite material bisphenol
A
CMC CMC/chitosan polyelectrolyte SBF 1.42 to ACP Drug delivery [96]
1.69
Cellulose acetate Cellulose acetate electrospun SBF – HA Candidate for tissue [97]
modified with the CMC engineering
Cellulose derivatives Polyanion, polycation, and Diammonium hydrogen phosphate Different HAP (at low concentration) [98]
polyzwitterion and calcium nitrate tetrahydrate ratios or DCPD
Hydroxyethyl HEC/polyvinyl alcohol nanofibers 10xSBF – Calcium phosphate hydrate Promising material [99]
cellulose and apatite for bone
Ethyl cellulose or CaCl2*2H2O and (NH4)2HPO4 N2 Amorphous calcium [100]
Hydroxypropyl phosphate and less ordered
cellulose HAP
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
of carboxyl groups originated from CMC adsorption on the electrospun
fibers. The study exhibited that surface chemical modification of the cel-
lulosic substrates can provide promising materials for bone regenera-
tion [97].
6.4.2. Other cellulose derivatives/calcium phosphate hybrids
Different cellulose derivatives were studied as growth modifier and
templates for biomimetic calcium phosphate mineralization. A. Taubert
et al. studied the effect of the charges presented on the cellulose surface
on the growth of calcium phosphate. Various water soluble cellulose de-
rivatives a polyanion, a polycation, and a polyzwitterion were studied
for the synthesis and design of bioinspired and bio-based hybrid mate-
rials. The authors studied three variables, polymer composition, poly-
mer concentration, and precursor concentration on the mineralization
process. The results showed that the precursor concentration controls
the phase of the precipitated calcium phosphate, either HAP (at low
concentration) or DCPD (at high concentration). This is independent
of the presence or absence of cellulose derivatives as additive. EDXs el-
emental analysis results exhibited that a higher cellulose derivative con-
centration enhances the formation of cellulose-enriched hybrids. This
study shows that water-soluble cellulose derivatives enhanced the
growth of true calcium phosphate/polymer “real” hybrid material [98].
Hydroxyethyl cellulose (HEC) is widely applied in various fields es-
pecially pharmaceutical industries. HEC, non-ionic and water soluble
polymer, is appropriate for bone tissue engineering applications. HEC
functionalized with bone-like calcium phosphate was prepared through
electrospinning and mineralized by incubating in concentrated SBF. The
mineralized HEC/polyvinyl alcohol hybrid improved cell proliferation
and was suggested as promising material for bone regeneration [99].
Chiral nematic liquid crystalline gels of (ethyl) cellulose/PAA and
(hydroxypropyl) cellulose/PAA in a film form were investigated as scaf-
folding medium for precipitation of calcium phosphate. Immersing the
cellulosic/PAA films in a salt solution containing calcium and phosphate
ions showed the growth of amorphous calcium phosphate and less or-
dered HAP. The results of the study revealed that the calcium phosphate
mineralization significantly improved the thermal and mechanical
properties of the optically functionalized cellulosic/synthetic polymer
composites [100].
It is clear from this review that using cellulose as a biomaterial for
calcium phosphate mineralization instead of synthetic polymers is a re-
cent trend in material science. There are some recent trials for preparing
specific cellulose/calcium phosphate hybrids that are promising candi-
dates for further materials development. It is clear that extended inves-
tigation of different cellulosic forms and cellulose derivatives will enable
a much better understanding of how hybrid materials formed through
biomineralization. Comparison of data obtained from different cellulose
derivatives suggests that cellulose solubility and functionality is the
main factors that control the nucleation and morphologies of the final
hybrid materials. In recognition of the many trials available from the lit-
erature, we have attempted to collect all cellulosic materials used for
preparing hybrid materials and to compile the most important informa-
tion into a table (Table 1).
7. Summary
Cellulose, the most abundant biopolymer, and its derivatives are
widely used for developing and constructing smart organic/inorganic
hybrid materials. Cellulose/calcium phosphate hybrid materials com-
bine the properties of both components, functionality and flexibility of
the cellulose with heat resistance and stability of the inorganic material.
This review summarizes and discusses the trials carried out to use cellu-
losic materials as promising candidate for bio-mimetic calcium phos-
phate mineralization. There has been an increasing interest for
applying cellulose/calcium phosphate hybrids in different biomedical
and environmental applications such as building high performance
and novel natural bone, drug delivery systems and adsorbents.
615
Moreover, increasing the functionality of cellulose through different
techniques to enhance the bioactivity of cellulosic materials towards
mineral nucleation and growth has significantly improved. These trials
suggest that cellulose/calcium phosphate hybrid materials could be-
come promising generation for environmental and biomedical applica-
tions. However, there is still a need to investigate much deeper into the
individual steps that lead to a useful well-defined complex cellulose/cal-
cium phosphate hybrids.
Acknowledgments
I thank Prof. Dr. Andreas Taubert from Potsdam University for
hosting me in his research group during my PhD, where I learned the
principles of calcium phosphate mineralization.
References
[1] S. Schweizer, A. Taubert, Polymer-controlled, bio-inspired calcium phosphate min-
eralization from aqueous solution, Macromol. Biosci. 7 (2007) 1085–1099, https://
doi.org/10.1002/mabi.200600283.
[2] A. Salama, M. Neumann, C. Günter, A. Taubert, Ionic liquid-assisted formation of
cellulose/calcium phosphate hybrid materials, Beilstein J. Nanotechnol. 5 (2014)
1553–1568, https://doi.org/10.3762/bjnano.5.167.
[3] A. Salama, New sustainable hybrid material as adsorbent for dye removal from
aqueous solutions, J. Colloid Interface Sci. 487 (2017) 348–353, https://doi.org/
10.1016/j.jcis.2016.10.034.
[4] C. Sanchez, K.J. Shea, S. Kitagawa, B. Julia, Applications of advanced hybrid organic–
inorganic nanomaterials: from laboratory to market, Chem. Soc. Rev. 40 (2011)
696–753, https://doi.org/10.1039/c0cs00069h.
[5] M.S. Islam, L. Chen, J. Sisler, K.C. Tam, Cellulose nanocrystal (CNC)-inorganic hybrid
systems: synthesis, properties and applications, J. Mater. Chem. B 6 (2018)
864–883, https://doi.org/10.1039/c7tb03016a.
[6] J. Chen, P. Pan, Y. Zhang, S. Zhong, Q. Zhang, Preparation of chitosan/nano hydroxy-
apatite organic-inorganic hybrid microspheres for bone repair, Colloids Surf. B:
Biointerfaces 134 (2015) 401–407, https://doi.org/10.1016/j.colsurfb.2015.06.072.
[7] A. Salama, P. Hesemann, Synthesis of N-guanidinium-chitosan/silica hybrid com-
posites: efficient adsorbents for anionic pollutants, J. Polym. Environ. 26 (2018)
1986–1997, https://doi.org/10.1007/s10924-017-1093-3.
[8] A. Salama, Polysaccharides/silica hybrid materials: new perspectives for sustain-
able raw materials, J. Carbohydr. Chem. 35 (2016) 131–149, https://doi.org/10.
1080/07328303.2016.1154152.
[9] A. Salama, Dicarboxylic cellulose decorated with silver nanoparticles as sustainable
antibacterial nanocomposite material, Environ. Nanotechnol. Monit. Manag. 8
(2017) 228–232, https://doi.org/10.1016/j.enmm.2017.08.003.
[10] C. Alvarez-Lorenzo, B. Blanco-Fernandez, A.M. Puga, A. Concheiro, Crosslinked ionic
polysaccharides for stimuli-sensitive drug delivery, Adv. Drug Deliv. Rev. 65 (2013)
1148–1171, https://doi.org/10.1016/j.addr.2013.04.016.
[11] A. Salama, P. Hesemann, New N-guanidinium chitosan/silica ionic microhybrids as
efficient adsorbent for dye removal from waste water, Int. J. Biol. Macromol. 111
(2018) 762–768, https://doi.org/10.1016/j.ijbiomac.2018.01.049.
[12] D. Klemm, B. Heublein, H.P. Fink, A. Bohn, Cellulose: fascinating biopolymer and
sustainable raw material, Angew. Chem. Int. Ed. 44 (2005) 3358–3393, https://
doi.org/10.1002/anie.200460587.
[13] R.J. Moon, A. Martini, J. Nairn, J. Simonsen, J. Youngblood, Cellulose Nanomaterials
Review: Structure, Properties and Nanocomposites, Chem. Soc. Rev. 40 (2011)
3941–3994, https://doi.org/10.1039/c0cs00108b.
[14] Y. Habibi, L.A. Lucia, O.J. Rojas, Cellulose nanocrystals: chemistry, self-assembly,
and applications, Chem. Rev. 110 (2010) 3479–3500, https://doi.org/10.1021/
cr900339w.
[15] S.C. Fox, B. Li, D. Xu, K.J. Edgar, Regioselective esterification and etherification of
cellulose: a review, Biomacromolecules 12 (2011) 1956–1972, https://doi.org/10.
1021/bm200260d.
[16] T. Heinze, O.A. El Seoud, A. Koschella, Cellulose Derivatives, Springer International
Publishing, Cham, 2018https://doi.org/10.1007/978-3-319-73168-1.
[17] J. Van Rie, W. Thielemans, Cellulose-gold nanoparticle hybrid materials, Nanoscale
9 (2017) 8525–8554, https://doi.org/10.1039/c7nr00400a.
[18] S. Mun, M. Maniruzzaman, H.-U. Ko, A. Kafy, J. Kim, Preparation and characterisa-
tion of cellulose ZnO hybrid film by blending method and its glucose biosensor ap-
plication, Mater. Technol. 30 (2015) B150–B154, https://doi.org/10.1179/
1753555714Y.0000000197.
[19] Y. Qiu, K. Park, Environment-sensitive hydrogels for drug delivery, Adv. Drug Deliv.
Rev. 53 (2001) 321–339, https://doi.org/10.1016/S0169-409X(01)00203-4.
[20] Y. Chujo, T. Saegusa, Organic polymer hybrids with silica gel formed by means of
the sol-gel method, Adv. Polym. Sci. 100 (1992) 11–29.
[21] C. Sanchez, K.J. Shea, S. Kitagawa, Recent progress in hybrid materials science,
Chem. Soc. Rev. 40 (2011) 471–472, https://doi.org/10.1039/c1cs90001c.
[22] K. Bleek, A. Taubert, New developments in polymer-controlled, bioinspired cal-
cium phosphate mineralization from aqueous solution, Acta Biomater. 9 (2013)
6283–6321, https://doi.org/10.1016/j.actbio.2012.12.027.
[23] C.-H. Lee, S.-H. Cheng, I.-P. Huang, J.S. Souris, C.-S. Yang, C.-Y. Mou, et al., Intracel-
lular pH-responsive mesoporous silica nanoparticles for the controlled release of
616 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
anticancer chemotherapeutics, Angew. Chem. Int. Ed. 49 (2010) 8214–8219,
https://doi.org/10.1002/anie.201002639.
[24] D.W. Green, S. Mann, R.O.C. Oreffo, Mineralized polysaccharide capsules as biomi-
metic microenvironments for cell, gene and growth factor delivery in tissue engi-
neering, Soft Matter 2 (2006) 732–737, https://doi.org/10.1039/b604786f.
[25] A. Salama, Chitosan based hydrogel assisted spongelike calcium phosphate miner-
alization for in-vitro BSA release, Int. J. Biol. Macromol. 108 (2018) 471–476,
https://doi.org/10.1016/j.ijbiomac.2017.12.035.
[26] S. Mahmoudian, M.U. Wahit, A.F. Ismail, A.A. Yussuf, Preparation of regenerated
cellulose/montmorillonite nanocomposite films via ionic liquids, Carbohydr.
Polym. 88 (2012) 1251–1257, https://doi.org/10.1016/j.carbpol.2012.01.088.
[27] M.G. Ma, Y.Y. Dong, L.H. Fu, S.M. Li, R.C. Sun, Cellulose/CaCO3 nanocomposites: mi-
crowave ionic liquid synthesis, characterization, and biological activity, Carbohydr.
Polym. 92 (2013) 1669–1676, https://doi.org/10.1016/j.carbpol.2012.11.034.
[28] G. Wang, L. Zheng, H. Zhao, J. Miao, C. Sun, H. Liu, et al., Construction of a fluores-
cent nanostructured chitosan-hydroxyapatite scaffold by nanocrystallon induced
biomimetic mineralization and its cell biocompatibility, ACS Appl. Mater. Interfaces
3 (2011) 1692–1701, https://doi.org/10.1021/am2002185.
[29] S.V. Dorozhkin, M. Epple, Biological and medical significance of calcium phos-
phates, Angew. Chem. Int. Ed. Eng. 41 (2002) 3130–3146, https://doi.org/10.
1002/1521-3773(20020902)41:17b3130::AID-ANIE3130N3.0.CO;2-1.
[30] S.V. Dorozhkin, Calcium orthophosphates, J. Mater. Sci. 42 (2007) 1061–1095,
https://doi.org/10.1007/s10853-006-1467-8.
[31] H. Cölfen, A crystal-clear view, Nat. Mater. 9 (2010) 960–961, https://doi.org/10.
1038/nmat2911.
[32] M. Kim, M. Yeo, M. Kim, G. Kim, Biomimetic cellulose/calcium-deficient-
hydroxyapatite composite scaffolds fabricated using an electric field for bone tis-
sue engineering, RSC Adv. 8 (2018) 20637–20647, https://doi.org/10.1039/
C8RA03657H.
[33] C. Busuioc, C.D. Ghitulica, A. Stoica, M. Stroescu, G. Voicu, V. Ionita, et al., Calcium
phosphates grown on bacterial cellulose template, Ceram. Int. 44 (2018)
9433–9441, https://doi.org/10.1016/j.ceramint.2018.02.160.
[34] L.L. Hench, Bioceramics: from concept to clinic, J. Am. Ceram. Soc. 74 (1991)
1487–1510, https://doi.org/10.1111/j.1151-2916.1991.tb07132.x.
[35] P. Cromme, C. Zollfrank, L. Müller, F.A. Müller, P. Greil, Biomimetic mineralisation
of apatites on Ca2+ activated cellulose templates, Mater. Sci. Eng. C 27 (2007)
1–7, https://doi.org/10.1016/j.msec.2005.11.001.
[36] M. Kawata, K. Azuma, H. Izawa, M. Morimoto, H. Saimoto, S. Ifuku, Biomineraliza-
tion of calcium phosphate crystals on chitin nanofiber hydrogel for bone regener-
ation material, Carbohydr. Polym. 136 (2015) 964–969, https://doi.org/10.1016/j.
carbpol.2015.10.009.
[37] X. Wang, J. Shi, Z. Li, S. Zhang, H. Wu, Z. Jiang, et al., Facile one-pot preparation of
chitosan/calcium pyrophosphate hybrid micro flowers, ACS Appl. Mater. Interfaces
6 (2014) 14522–14532, https://doi.org/10.1021/am503787h.
[38] D. Das, S. Zhang, I. Noh, Synthesis and characterizations of alginate-α-tricalcium
phosphate microparticle hybrid film with flexibility and high mechanical property
as a biomaterial, Biomed. Mater. 13 (2018) 30–33, https://doi.org/10.1088/1748-
605X/aa8fa1.
[39] M. Joglekar, B.G. Trewyn, Polymer-based stimuli-responsive nanosystems for bio-
medical applications, Biotechnol. J. 8 (2013) 931–945, https://doi.org/10.1002/
biot.201300073.
[40] N.X. Wang, H.A. von Recum, Affinity-based drug delivery, Macromol. Biosci. 11
(2011) 321–332, https://doi.org/10.1002/mabi.201000206.
[41] D. Bhowmik, H. Gopinath, B.P. Kumar, S. Duraivel, K.P.S. Kumar, Controlled release
drug delivery systems, Pharm. Innov. 1 (2012) 24–32.
[42] W.S. Wan Ngah, L.C. Teong, M.A.K.M. Hanafiah, Adsorption of dyes and heavy
metal ions by chitosan composites: a review, Carbohydr. Polym. 83 (2011)
1446–1456, https://doi.org/10.1016/j.carbpol.2010.11.004.
[43] A. Salama, Preparation of CMC-g-P(SPMA) super adsorbent hydrogels: exploring
their capacity for MB removal from waste water, Int. J. Biol. Macromol. 106
(2018) 940–946, https://doi.org/10.1016/j.ijbiomac.2017.08.097.
[44] M. Monier, D.A. Abdel-Latif, Preparation of cross-linked magnetic chitosan-
phenylthiourea resin for adsorption of Hg(II), Cd(II) and Zn(II) ions from aqueous
solutions, J. Hazard. Mater. 209–210 (2012) 240–249, https://doi.org/10.1016/j.
jhazmat.2012.01.015.
[45] A. Salama, S. Etri, S.A.A. Mohamed, M. El-Sakhawy, Carboxymethyl cellulose pre-
pared from mesquite tree: new source for promising nanocomposite materials,
Carbohydr. Polym. 189 (2018) 138–144, https://doi.org/10.1016/j.carbpol.2018.
02.016.
[46] H. Hou, R. Zhou, P. Wu, L. Wu, Removal of Congo red dye from aqueous solution
with hydroxyapatite/chitosan composite, Chem. Eng. J. 211–212 (2012) 336–342,
https://doi.org/10.1016/j.cej.2012.09.100.
[47] N. Barka, S. Qourzal, A. Assabbane, A. Nounah, Y. Alt-ichou, Adsorption of Disperse
Blue SBL dye by synthesized poorly crystalline hydroxyapatite, J. Environ. Sci. 20
(2008) 1268–1272, https://doi.org/10.1016/S1001-0742(08)62220-2.
[48] H. El Boujaady, A. El Rhilassi, M. Bennani-Ziatni, R. El Hamri, A. Taitai, J.L. Lacout,
Removal of a textile dye by adsorption on synthetic calcium phosphates, Desalina-
tion 275 (2011) 10–16, https://doi.org/10.1016/j.desal.2011.03.036.
[49] E. Safwat, M.L. Hassan, S. Saniour, D.Y. Zaki, M. Eldeftar, D. Saba, et al., Injectable
TEMPO-oxidized nanofibrillated cellulose/biphasic calcium phosphate hydrogel
for bone regeneration, J. Biomater. Appl. 32 (2018) 1371–1381, https://doi.org/
10.1177/0885328218763866.
[50] S. Sotome, T. Uemura, M. Kikuchi, J. Chen, S. Itoh, J. Tanaka, et al., Synthesis and
in vivo evaluation of a novel hydroxyapatite/collagen–alginate as a bone filler
and a drug delivery carrier of bone morphogenetic protein, Mater. Sci. Eng. C 24
(2004) 341–347, https://doi.org/10.1016/j.msec.2003.12.003.
[51] H. Wang, Y. Li, Y. Zuo, J. Li, S. Ma, L. Cheng, Biocompatibility and osteogenesis of
biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue
engineering, Biomaterials 28 (2007) 3338–3348, https://doi.org/10.1016/j.
biomaterials.2007.04.014.
[52] K. Higashi, T. Kondo, Nematic ordered cellulose templates mediating order-
patterned deposition accompanied with synthesis of calcium phosphates, Cellu-
lose 19 (2012) 81–90, https://doi.org/10.1007/s10570-011-9627-7.
[53] M. González, E. Hernández, J.A. Ascencio, F. Pacheco, S. Pacheco, R. Rodríguez, Hy-
droxyapatite crystals grown on a cellulose matrix using titanium alkoxide as a cou-
pling agent, J. Mater. Chem. 13 (2003) 2948–2951, https://doi.org/10.1039/
b306846n.
[54] M. Isik, H. Sardon, D. Mecerreyes, Ionic liquids and cellulose: dissolution, chemical
modification and preparation of new cellulosic materials, Int. J. Mol. Sci. 15 (2014)
11922–11940, https://doi.org/10.3390/ijms150711922.
[55] O.A. El Seoud, A. Koschella, L.C. Fidale, S. Dorn, T. Heinze, Applications of ionic liq-
uids in carbohydrate chemistry: a window of opportunities, Biomacromolecules 8
(2007) 2629–2647, https://doi.org/10.1021/bm070062i.
[56] H. Wang, G. Gurau, R.D. Rogers, Ionic liquid processing of cellulose, Chem. Soc. Rev.
41 (2012) 1519–1537, https://doi.org/10.1039/c2cs15311d.
[57] Y. Zhou, J. Schattka, Room-temperature ionic liquids as template to monolithic
mesoporous silica with wormlike pores via a sol-gel nanocasting technique,
Nano Lett. 4 (2004) 477–481http://pubs.acs.org/doi/abs/10.1021/nl025861f,
Accessed date: 24 June 2012.
[58] H. Kaper, F. Endres, I. Djerdj, M. Antonietti, B.M. Smarsly, J. Maier, et al., Direct low-
temperature synthesis of rutile nanostructures in ionic liquids, Small 3 (2007)
1753–1763, https://doi.org/10.1002/smll.200700138.
[59] A. Taubert, CuCl nanoplatelets from an ionic liquid-crystal precursor, Angew.
Chem. 116 (2004) 5494–5496, https://doi.org/10.1002/ange.200460846.
[60] E.R. Parnham, R.E. Morris, Ionothermal synthesis of zeolites, metal-organic frame-
works, and inorganic-organic hybrids, Acc. Chem. Res. 40 (2007) 1005–1013,
https://doi.org/10.1021/ar700025k.
[61] A. Taubert, Z. Li, Inorganic materials from ionic liquids, Dalton Trans. (2007)
723–727, https://doi.org/10.1039/b616593a.
[62] A. Salama, M. El-Sakhawy, Regenerated cellulose/wool blend enhanced biomimetic
hydroxyapatite mineralization, Int. J. Biol. Macromol. 92 (2016) 920–925, https://
doi.org/10.1016/j.ijbiomac.2016.07.077.
[63] A. Salama, N. Shukry, A. El-gendy, M. El-sakhawy, Bioactive cellulose grafted soy
protein isolate towards biomimetic calcium phosphate mineralization, Ind. Crop.
Prod. 95 (2017) 170–174, https://doi.org/10.1016/j.indcrop.2016.10.019.
[64] J. Yang, C.-R. Han, X.-M. Zhang, F. Xu, R.-C. Sun, Cellulose nanocrystals mechanical
reinforcement in composite hydrogels with multiple cross-links: correlations be-
tween dissipation properties and deformation mechanisms, Macromolecules 47
(2014) 4077–4086, https://doi.org/10.1021/ma500729q.
[65] T. Taflick, L.A. Schwendler, S.M.L. Rosa, C.I.D. Bica, S.M.B. Nachtigall, Cellulose
nanocrystals from acacia bark–influence of solvent extraction, Int. J. Biol.
Macromol. 101 (2017) 553–561, https://doi.org/10.1016/j.ijbiomac.2017.03.
076.
[66] M.L. Hassan, R.E.A. Zeid, S.M. Fadel, M. El Sakhawy, R. Khiari, Cellulose nanocrystals
and carboxymethyl cellulose from olive stones and their use to improve paper
sheets properties, Int. J. Nanoparticles 7 (2014) 261–277, https://doi.org/10.
1504/IJNP.2014.067613.
[67] S.K. Rahimi, J.U. Otaigbe, Green hybrid composites from cellulose nanocrystal, Hy-
brid Polym. Compos. Mater, Elsevier 2017, pp. 65–99, https://doi.org/10.1016/
B978-0-08-100791-4.00004-5.
[68] C. Olivier, J.B. Mougel, P. Bertoncini, C. Moreau, I. Capron, B. Cathala, et al., Carbon
nanotube/cellulose nanocrystal hybrid conducting thin films, J. Renew. Mater. 6
(2017) 237–241, https://doi.org/10.7569/JRM.2017.634168.
[69] E.H. Fragal, T.S.P. Cellet, V.H. Fragal, M.V.P. Companhoni, T. Ueda-Nakamura, E.C.
Muniz, et al., Hybrid materials for bone tissue engineering from biomimetic
growth of hydroxiapatite on cellulose nanowhiskers, Carbohydr. Polym. 152
(2016) 734–746, https://doi.org/10.1016/j.carbpol.2016.07.063.
[70] M. Ishikawa, Y. Oaki, Y. Tanaka, H. Kakisawa, G. Salazar-Alvarez, H. Imai, Fabrica-
tion of nanocellulose-hydroxyapatite composites and their application as water-
resistant transparent coatings, J. Mater. Chem. B 3 (2015) 5858–5863, https://doi.
org/10.1039/c5tb00927h.
[71] M. Hassan, R. Abou-Zeid, E. Hassan, L. Berglund, Y. Aitomäki, K. Oksman, Mem-
branes based on cellulose nanofibers and activated carbon for removal of
Escherichia coli bacteria from water, Polymers 9 (2017) 335–349, https://doi.
org/10.3390/polym9080335 (Basel).
[72] R.E. Abouzeid, R. Khiari, D. Beneventi, A. Dufresne, Biomimetic mineralization of
three-dimensional printed alginate/TEMPO-oxidized cellulose nanofibril scaffolds
for bone tissue engineering, Biomacromolecules 19 (2018) 4442–4452, https://
doi.org/10.1021/acs.biomac.8b01325.
[73] S. Morimune-Moriya, S. Kondo, A. Sugawara-Narutaki, T. Nishimura, T. Kato, C.
Ohtsuki, Hydroxyapatite formation on oxidized cellulose nanofibers in a solution
mimicking body fluid, Polym. J. 47 (2015) 158–163, https://doi.org/10.1038/pj.2014.
127.
[74] H.-I. Jung, O.-M. Lee, J.-H. Jeong, Y.-D. Jeon, K.-H. Park, H.-S. Kim, et al., Production
and characterization of cellulose by Acetobacter sp. V6 using a cost-effective
molasses–corn steep liquor medium, Appl. Biochem. Biotechnol. 162 (2010)
486–497, https://doi.org/10.1007/s12010-009-8759-9.
[75] M.A. Mohamed, M. Abd Mutalib, Z.A. Mohd Hir, M.F.M. Zain, A.B. Mohamad, L.
Jeffery Minggu, et al., An overview on cellulose-based material in tailoring bio-
hybrid nanostructured photocatalysts for water treatment and renewable energy
applications, Int. J. Biol. Macromol. 103 (2017) 1232–1256, https://doi.org/10.
1016/j.ijbiomac.2017.05.181.
 A. Salama / International Journal of Biological Macromolecules 127 (2019) 606–617
[76] M. Ul-Islam, W.A. Khattak, M.W. Ullah, S. Khan, J.K. Park, Synthesis of regenerated
bacterial cellulose-zinc oxide nanocomposite films for biomedical applications,
Cellulose 21 (2014) 433–447, https://doi.org/10.1007/s10570-013-0109-y.
[77] G.F. Picheth, C.L. Pirich, M.R. Sierakowski, M.A. Woehl, C.N. Sakakibara, C.F. de
Souza, et al., Bacterial cellulose in biomedical applications: a review, Int. J. Biol.
Macromol. 104 (2017) 97–106, https://doi.org/10.1016/j.ijbiomac.2017.05.171.
[78] W.-C. Lin, C.-C. Lien, H.-J. Yeh, C.-M. Yu, S. Hsu, Bacterial cellulose and bacterial
cellulose–chitosan membranes for wound dressing applications, Carbohydr.
Polym. 94 (2013) 603–611, https://doi.org/10.1016/j.carbpol.2013.01.076.
[79] K. Qiu, A.N. Netravali, A review of fabrication and applications of bacterial cellulose
based nanocomposites, Polym. Rev. 54 (2014) 598–626, https://doi.org/10.1080/
15583724.2014.896018.
[80] M. Abrigo, S.L. McArthur, P. Kingshott, Electrospun nanofibers as dressings for
chronic wound care: advances, challenges, and future prospects, Macromol. Biosci.
14 (2014) 772–792, https://doi.org/10.1002/mabi.201300561.
[81] C. Busuioc, M. Stroescu, A. Stoica-Guzun, G. Voicu, S.I. Jinga, Fabrication of 3D cal-
cium phosphates based scaffolds using bacterial cellulose as template, Ceram. Int.
42 (2016) 15449–15458, https://doi.org/10.1016/j.ceramint.2016.06.196.
[82] Y.Z. Wan, Y. Huang, C.D. Yuan, S. Raman, Y. Zhu, H.J. Jiang, et al., Biomimetic synthe-
sis of hydroxyapatite/bacterial cellulose nanocomposites for biomedical applica-
tions, Mater. Sci. Eng. C 27 (2007) 855–864, https://doi.org/10.1016/j.msec.2006.
10.002.
[83] T. Kokubo, H. Takadama, How useful is SBF in predicting in vivo bone bioactivity?
Biomaterials 27 (2006) 2907–2915, https://doi.org/10.1016/j.biomaterials.2006.
01.017.
[84] S. Hutchens, R. Benson, B. Evans, H. Oneill, C. Rawn, Biomimetic synthesis of
calcium-deficient hydroxyapatite in a natural hydrogel, Biomaterials 27 (2006)
4661–4670, https://doi.org/10.1016/j.biomaterials.2006.04.032.
[85] G.V.G. Cornelis, G. Sarah, The biodegredability and nontoxicity of carboxymethyl
celulose (DS 0.7) and intermediates, Environ. Toxicol. Chem. 15 (1996) 270–274.
[86] Z. Rao, H. Ge, L. Liu, C. Zhu, L. Min, M. Liu, et al., Carboxymethyl cellulose modified
graphene oxide as pH-sensitive drug delivery system, Int. J. Biol. Macromol. 107
(2018) 1184–1192, https://doi.org/10.1016/j.ijbiomac.2017.09.096.
[87] S. Shankar, A.A. Oun, J.-W. Rhim, Preparation of antimicrobial hybrid nano-
materials using regenerated cellulose and metallic nanoparticles, Int. J. Biol.
Macromol. 107 (2018) 17–27, https://doi.org/10.1016/j.ijbiomac.2017.08.129.
[88] D. Pasqui, P. Torricelli, M. De Cagna, M. Fini, R. Barbucci, Carboxymethyl cellulose -
hydroxyapatite hybrid hydrogel as a composite material for bone tissue engineer-
ing applications, J. Biomed. Mater. Res. A 102 (2014) 1568–1579, https://doi.org/
10.1002/jbm.a.34810.
[89] A. Salama, R.E. Abou-Zeid, M. El-Sakhawy, A. El-Gendy, Carboxymethyl cellulose/
silica hybrids as templates for calcium phosphate biomimetic mineralization, Int.
617
J. Biol. Macromol. 74 (2015) 155–161, https://doi.org/10.1016/j.ijbiomac.2014.11.
041.
[90] A. Salama, Carboxymethyl cellulose-g-poly (acrylic acid)/calcium phosphate com-
posite as a multifunctional hydrogel material, Mater. Lett. 157 (2015) 243–247,
https://doi.org/10.1016/j.matlet.2015.05.088.
[91] A. Salama, M. El-Sakhawy, S. Kamel, Carboxymethyl cellulose based hybrid mate-
rial for sustained release of protein drugs, Int. J. Biol. Macromol. 93 (2016)
1647–1652, https://doi.org/10.1016/j.ijbiomac.2016.04.029.
[92] A. Salama, R.E. Abou-Zeid, M. El-Sakhawy, Calcium phosphate mineralization con-
trolled by carboxymethyl cellulose-g-polymethacrylic acid, Soft Mater. 14 (2016)
154–161, https://doi.org/10.1080/1539445X.2016.1171781.
[93] A. Salama, Functionalized hybrid materials assisted organic dyes removal from
aqueous solutions, Environ. Nanotechnol. Monit. Manag. 6 (2016) 159–163,
https://doi.org/10.1016/j.enmm.2016.10.003.
[94] P. Qi, S. Ohba, Y. Hara, M. Fuke, T. Ogawa, S. Ohta, et al., Fabrication of calcium
phosphate-loaded carboxymethyl cellulose non-woven sheets for bone regenera-
tion, Carbohydr. Polym. 189 (2018) 322–330, https://doi.org/10.1016/j.carbpol.
2018.02.050.
[95] K. Azzaoui, E. Mejdoubi, A. Lamhamdi, S. Jodeh, O. Hamed, M. Berrabah, et al., Prep-
aration and characterization of biodegradable nanocomposites derived from
carboxymethyl cellulose and hydroxyapatite, Carbohydr. Polym. 167 (2017)
59–69, https://doi.org/10.1016/j.carbpol.2017.02.092.
[96] A. Salama, M. El-Sakhawy, Preparation of polyelectrolyte/calcium phosphate hy-
brids for drug delivery application, Carbohydr. Polym. 113 (2014) 500–506,
https://doi.org/10.1016/j.carbpol.2014.07.022.
[97] K. Rodríguez, S. Renneckar, P. Gatenholm, Biomimetic calcium phosphate crystal
mineralization on electrospun cellulose-based scaffolds, ACS Appl. Mater. Inter-
faces 3 (2011) 681–689, https://doi.org/10.1021/am100972r.
[98] A. Taubert, C. Balischewski, D. Hentrich, T. Elschner, S. Eidner, C. Günter, et al.,
Water-soluble cellulose derivatives are sustainable additives for biomimetic cal-
cium phosphate mineralization, Inorganics 4 (2016) 33, https://doi.org/10.3390/
inorganics4040033.
[99] S. Chahal, F.S. Jahir Hussain, A. Kumar, M.M. Yusoff, M.S. Bahari Abdull Rasad,
Electrospun hydroxyethyl cellulose nanofibers functionalized with calcium phos-
phate coating for bone tissue engineering, RSC Adv. 5 (2015) 29497–29504,
https://doi.org/10.1039/c4ra17087c.
[100] T. Ogiwara, A. Katsumura, K. Sugimura, Y. Teramoto, Y. Nishio, Calcium phosphate
mineralization in cellulose derivative/poly(acrylic acid) composites having a chiral
nematic mesomorphic structure, Biomacromolecules 16 (2015) 3959–3969,
https://doi.org/10.1021/acs.biomac.5b01295.