REVIEWS

The potential of 3D printing in

urological research and patient care
Marc Colaco1, Daniel A. Igel2 and Anthony Atala1,3
Abstract | 3D printing is an evolving technology that enables the creation of unique organic and
inorganic structures with high precision. In urology, the technology has demonstrated potential
uses in both patient and clinician education as well as in clinical practice. The four major
techniques used for 3D printing are inkjet printing, extrusion printing, laser sintering, and
stereolithography. Each of these techniques can be applied to the production of models for
education and surgical planning, prosthetic construction, and tissue bioengineering.
Bioengineering is potentially the most important application of 3D printing, as the ability to
produce functional organic constructs might, in the future, enable urologists to replicate and
replace abnormal tissues with neo-organs, improving patient survival and quality of life.

1
Department of Urology,
Wake Forest School
of Medicine.
2
Wake Forest School
of Medicine.
3
Wake Forest Institute for
Regenerative Medicine;
Wake Forest School of
Medicine, Medical Center
Blvd., Winston-Salem,
NC 27157, USA.
Correspondence to M.C.
mcolaco@wakehealth.edu
doi:10.1038/nrurol.2018.6
Published online 6 Feb 2018
“Any customer can have a car painted in any colour that
he wants so long as it is black” (REF. 1). This excerpt from
industry tycoon Henry Ford illustrates the manufactur-
ing process brought about by standardization and pro-
duction lines, wherein mass production by tooling and
stepwise assembly made amenities, such as automobiles
and appliances, accessible to the general population. This
process sacrificed the personalization and craftsmanship
of bespoke construction, but it enabled production of a
wide variety of goods at affordable prices and in a vol-
ume that was unprecedented. This paradigm of produc-
tion persists and is the basis of the modern consumer
economy. However, homogeneity of the fabricated goods
is inherent to assembly-line mass production. In 1986,
a technique, termed stereolithography, was described
that used ultraviolet light to sequentially harden layers
of plastics or other polymers from a liquid bath to gen-
erate complex 3D structures2. This technology had the
potential to create unique structures while maintaining
the precision and high throughput of assembly-line
manufacturing.
Since that time, several 3D printing methods have
been developed for which a variety of applications
have been found, including creating prototypes of new
products, fabricating architectural models, and rapidly
generating replacement parts and other products for
consumers. The medical field in particular has been
an early adopter of 3D modelling technology. 3D con-
structs are used in various specialties, including ophthal­
mology 3 and orthopaedic surgery 4. Early adopters used
computer-assisted milling machines to create computer-­
generated surgical models as early as 1980 (REF. 5), and
the use of these machines to generate orthopaedic
endoprostheses was reported as early as 1983 (REF. 6).
These techniques generated constructs by a subtractive
method from a block of substrate rather than an addi-
tive method as used in printing technologies, but they
set the stage for the implementation of products created
using printing technologies. The early constructs had to
provide only structural support and, therefore, were the
most easily modelled and produced. Implementation
of 3D‑printed objects in urology and other specialties
that involve soft tissue has lagged, owing to the need
for dynamic constructs with the ability to conform to
multiple states. Additionally, urological bioengineering
applications of 3D printing require solid and hollow
viscous organs, such as the bladder, ureter, or kidney,
and fabrication of such structures adds a further level
of complexity.
In this Review, we describe the three principle appli-
cations of 3D printing that are relevant to urology and
have demonstrable or anticipated medical applications:
the use of 3D printing to generate inorganic models for
surgical planning and education; the use of 3D printing
for the production of inorganic prostheses and devices;
and the current and future use of 3D printing for bio-
engineering of organic structures. We also provide an
overview of the four printing technologies that are most
commonly used for medical applications.
3D printing techniques
All 3D printing processes start with the design of a vir-
tual model regardless of the printing technique used.
This step includes collecting size and tensile require-
ments for a construct and entering them into a 3D mod-
elling software. For the generation of medical constructs,

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Key points created by modifying home desktop 3D printers that

• 3D printing is a technology that has been used in manufacturing for a few decades
and multiple medical fields have adopted this technology for the creation of both
inorganic and organic constructs
• Inkjet printing, extrusion printing, laser sintering, and stereolithography, each with its
own advantages and disadvantages, are the four major techniques used for
3D printing
• 3D printers were previously expensive, but new models can now be purchased from
~US$300; the printing times can be highly variable depending on the desired
resolution of the construct
• In urology, 3D printing is currently being applied to create implantable devices such
as ureteral stents, as well as inorganic models for surgical planning
• Animal studies are already underway for the creation of 3D organic constructs that
are intended to replace vital organs, including the bladder, kidneys, and urethra
• The goal of bioprinting 3D organic constructs is to provide a personalized solution for
organ replacement, alleviating the shortage of suitable transplant organs and
associated complications
size requirements are often generated through medical
imaging, such as CT and MRI. Modern imaging software
generally saves files in the digital imaging and communi-
cations in medicine (DICOM) format and is the standard
for most hospital information technology setups. Modern
3D modelling packages, such as Mimics (Materialise,
Belgium)7 or OsiriX (Pixmeo, Switzerland)8, are able to
convert these data into the stereo­lithography (.stl) format
that is used by 3D printers. These files can be produced
using DICOM data from both CT and MRI with equal
efficacy. Once the model has been created, four differ-
ent techniques can be used to create the construct: inkjet
printing; extrusion printing; laser-assisted sintering; or
stereolithography 9 (FIG. 1).
cost as little as US$300, making them widely available
for experimentation14. They also have fast printing times
(up to 10,000 droplets per second)10. Depending on the
desired resolution, printing times are highly variable, but
for biological constructs requiring high resolution, drop-
lets generally are 5–50 μm in diameter; hence, to produce
constructs on the scale of centimetres requires around
100 million droplets and 3 hours per cm (REFS 2,15).
Acoustic printers generate the force for droplet
release through the pressure wave generated either
by sending voltage through a piezoelectric crystal16 or by
using an ultrasound generator 17. These machines have
an advantage over thermal printers, as pressure waves
enable more precise droplet sizes and direction of extru-
sion. This process also enables biological substrates to
be extruded in a gradient by altering droplet size, pro-
viding the possibility of modifying the superstructure
of the printed object, which can be important for recon-
struction of spatial patterns, such as those of hormones
in wound healing 18,19. Similar to thermal printing, the
acoustic technique has the potential risk of pressure fre-
quencies causing cell damage within the biological sub-
strate, but viable biological skin constructs have been
generated with this method17,20.
Extrusion printing. Extrusion printing is another in­­
expensive and widely available method for printing bio-
logical and nonbiological materials. Extrusion printers
work by applying pneumatic pressure to force a poly-
mer through a syringe-like extrusion head. In contrast
to inkjet printing, which requires the substrate to be
liquid enough to form droplets, this technique enables
production using continuous beads of material and

Inkjet printing. Printing with the inkjet technique is

similar to printing with a standard inkjet printer; how-
ever, instead of using printer ink that is deposited in a
single 2D layer, the machine deposits successive layers
of substrate to create 3D constructs. Furthermore, if
bio­logical objects are manufactured, bio-ink composed
of the appropriate cells, extracellular matrix, and other
organic components is used10. The bio-ink is delivered
drop by drop from a bio-ink cartridge until the structure
is fabricated11. The inks are composed from a hydrogel
base owing to its high water content, low toxicity profile,
and ability to handle the temperature and pressure asso-
ciated with the printing process12. The functional cells
for the target tissue are embedded into these matrices.
3D inkjet printers are classified as thermal or acoustic on
the basis of their extrusion force.
Thermal printers function by electrically heating
the print head to produce pulses of pressure that force
droplets from the nozzle. Using these printers for bio-
logical materials was initially met with concern, as they
were thought to generate undue mechanical stress on
the substrate, but various studies have demonstrated
that the localized heating does not have a substantial
effect on the stability or viability of biological printing
media, including those of neural cells13. These machines
are inexpensive and, for some applications, can be
Figure 1 | 3D printing techniques. After creation of a ▶
virtual 3D model, four different 3D printing techniques can
be used to create the construct.  A | Inkjet printers are
classified as thermal or acoustic on the basis of their
extrusion force. In thermal printers, the print head is
electrically heated to produce pressure pulses that force
droplets from the nozzle. In acoustic printers, the force for
droplet release is generated by a pressure wave, for
example, by sending voltage through a piezoelectric
actuator. Different substrates can be printed using the
same print head. Ba | In extrusion printers, the dispensing
force is created through air-pressure-driven pneumatic
extrusion or mechanical, piston-based extrusion, forcing
the substrate through a syringe-like extrusion head.
Bb | Extruded tubes of a cell-containing hydrogel mature
over time into cellularized tubes, in which the hydrogel has
been replaced by extracellular matrix (ECM).
C | In laser sintering of organic components, the energy
source (for example, a laser) is directed at a transparent
carrier ribbon that has the desired substrate on its
underside. The biomaterial is then propelled onto a
collecting dish, enabling stepwise production of a 3D
construct. D | In stereolithography, a focused energy beam
selectively heats an area in a bath of a liquid polymer. As
the heated area of the polymer hardens, the completed
layer gradually descends, and the next layer is created from
the overlying substrate. Figure adapted with permission
from REF. 9, Springer.

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Piezoelectric
Heater actuator

Polymer droplet

Stage

Ba Bb

Pneumatic Piston

5 mm 2.5 mm

Stage Printed Cellularized ECM-

tube 4 weeks containing tube

C
Laser

Laser pulse
Transparent
carrier
Ribbon
with cells
Printed
biomaterial
with cell
Stage

D Laser

Layer 2
Layer 1

Stage
Resin
Reservoir

Lowering of stage

Nature Reviews | Urology

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viscous substrates. The material dispensing force is cre-
ated through air-pressure-driven pneumatic extrusion21
or mechanical, piston-based extrusion22. The substrate
can either be fed by a liquid reservoir or, as is the case
in fused filament fabrication, from a filament of sub-
strate that is heated and liquefied by the extrusion head
immediately before deposition.
The primary advantage of extrusion printing over
inkjet printing is the ability to print with highly viscous
substrates. In bioprinting, substrates with high cell densi-
ties can be required to achieve physiological density levels
in printed constructs; hence, extrusion printing seems
particularly suitable. However, owing to the increased
pressure and shear stress put on the substrate, extrusion
printing results in lower cellular viability (50–80%) than
inkjet printing 23. This disadvantage can be remedied by
using reduced pressure and an increased extrusion nozzle
size, but these strategies result in reduced resolution in
the printed object. Furthermore, with a printing speed of
10–50 μm per second, extrusion printing is much slower
than inkjet printing (5–50 μm per droplet)10.
Laser sintering. Selective laser sintering and related
techniques that are classified as powder bed fusion are
other approaches to 3D printing currently employed
in medical disciplines. This technology was tradition-
ally used in nonbiological printing, for example, with
metals, but it is increasingly also being used for bio-
logical substrates10. For inorganic constructs, laser sin-
tering printers function by focusing a high-­powered
energy beam into a powdered substrate, causing
fusion of the substrate into the desired shape. Once
a layer of substrate has been sintered, a new layer of
substrate is added on top of the developing construct,
and energy is again applied. Laser sintering of organic
components functions slightly differently. In this
process, the energy source is selectively directed at a
transparent carrier ribbon with the desired substrate
on the underside. When the energy of the laser is applied
to the ribbon, it propels the substrate onto a collecting
dish, producing a 3D construct in a stepwise fashion24,25.
In comparison with inkjet or extrusion printing, an
advantage of laser sintering is that it does not require a
printer head and, therefore, does not suffer from poten-
tial clogging. However, the small printing volume of each
laser pulse makes it very time consuming, especially for
large tissues. Furthermore, for constructs that require
multiple substrates, each substrate would require a sepa­
rately prepared ribbon, further increasing production
time. However, following preparation, the printing pro-
cess itself is relatively fast and can cover up to 1,600 mm
per second10.
Stereolithography. In stereolithography, a focused
ultraviolet beam, laser, or other energy source is used to
selectively heat an area in a bath of liquid polymer. As
the heated area of the polymer hardens, the completed
layer gradually either moves out of the bath or descends
depending on the production configuration, and the
focused energy beam renders the next layer according
to the shape and size of the object being printed2.
Stereolithography is mainly used for the production
of nonbiological constructs, but it is increasingly being
used to create cell-free biological scaffolds and, in the
past 5 years, cell-containing scaffolds26. Systems to create
biological constructs employ alternative energy sources
for hardening to avoid the damage that ultraviolet light
would cause to cellular substrates. Stereolithography
remains uncommon for bioprinting applications and
can be a very slow process, dependent on the employed
substrate; thus, this technology is unlikely to see
large-scale use in the future.
Applications of 3D printing in urology
3D printing in surgical planning and education. The
advent of advanced 3D imaging modalities, such as MRI,
CT, and ultrasonography, enables the early identification
of pathological developments, as well as the planning
and execution of minimally invasive and increasingly
complex surgical procedures27. Similarly, 3D printing
has the potential to be increasingly important in sur-
gical planning, in training residents and students, and
in educating patients about complicated conditions
and procedures. 3D printing currently enables the crea-
tion of models with features that are unique to a patient’s
anatomy, including aberrant vasculature and specific
tumour locations and dimensions. The 3D‑printed
representations are derived from a patient’s individual
imaging data on the basis of CT and MRI. These models
enable evaluation of a patient’s anatomy in its actual 3D
form and surgical planning in a more realistic manner
than review of imaging findings alone. In addition, the
personalized constructs can inform robotic, laparo­
scopic, and endoscopic systems for patient-specific
surgical simulation, providing an unprecedented edu-
cational opportunity in both safety and effectiveness, as
trainees can learn and practise on the unique anatomy
of a patient before an actual incision is made. Finally,
these models can be used during consultation visits to
help patients better understand their disease and treat-
ment plans by enabling patients and their relatives to see
and feel the affected area in a manner that is much more
accessible than reviewing CT or MRI images.
When a high degree of precision is required, for
example, in urological procedures such as nerve-sparing
radical prostatectomy, partial nephrectomy, and uretero­
scopic lithotripsy, 3D‑printed constructs can provide
essential additional visualization of anatomical varia-
tions and the extent of pathological alterations. The use
of a 3D‑printed model to plan a precise bilateral partial
adrenal­ectomy for primary macronodular adrenal hyper-
plasia enabled the surgical team to obtain the exact sur-
gical margins desired, resulting in restoration of normal
endocrine function in the patient28. 3D printing of unique
patient anatomy has also been applied to the simulation
of robotic-assisted laparoscopic partial neph­rectomy in
patients with complex tumours with accurate simulation
of enucleation time and tumour dimensions to facili-
tate precise resection. In one study from 2017, tumour
dimensions in the 3D‑printed construct were almost
identical to those estimated in the computer-­generated
model (average construct volume was 38.50 mm3 and

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average computer model volume was 38.88 mm3)29. These
dimensions were statistically similar to those of the actual
tumours (the average volume of pathology specimens
was 41.79 mm3). The vasculature of the kidney can also
be accurately represented with 3D printing, enabling
an improved understanding of anatomical variations
in renal vasculature. This application has been used
experimentally in off-clamp robot-assisted laparoscopic
partial nephrectomies. In one study, 3D‑printed mod-
els were used to aid partial nephrectomy in ten patients
with renal tumours with R.E.N.A.L. nephrometry scores
≥8. All patients had acceptable perioperative outcomes
and negative surgical margins. The models were nearly
identical to the tumours, and patients felt that their use
provided them with a better understanding of their
condition30. Similar approaches would undoubtedly be
useful for renal transplants and other procedures involv-
ing renal vasculature. In addition, early results of the
use of 3D‑printed prostate models for planning resec-
tion of high-Gleason-score tumours in close proximity
to the prostatic capsule and neurovascular bundle have
been published (FIG. 2). In this proof‑of‑concept study,
five patients with MRI-demonstrated prostate imaging
reporting and data system (PIRADS) 4 or 5 lesions and
biopsy-proven cancer had models created that demon-
strated the size and location of their index lesion31. These
models were then used to determine the nearness of the
lesion to the neurovascular bundle and subsequently
the possibility of performing a nerve-sparing surgery.
The researchers reported a high degree of accuracy of
pathological margins between the model and the patient’s
tumour; hence, this approach is promising in aiding
technically complex nerve-sparing radical prostatectomy.
In addition to accurately replicating tumour texture
and dimensions in simulation, 3D‑printed models have
been shown to objectively increase trainee understand-
ing of patient anatomy and pathology without com-
promising patient safety or comfort. In one study,
trainees assigned R.E.N.A.L. nephrometry scores
(which require measurements of a tumour’s radius,
exophytic properties, nearness to the collecting system,
anterior positioning, and location relative to poles)
to six patients with increased accuracy when using
3D‑printed kidney models of renal cell carcinoma com-
pared with imaging alone (P < 0.1)32. Interpretation of
the models resulted in less inter-rater variability than
CT image interpretation, including no significant
difference in identification of exophytic properties,
which can determine surgical approach and poten-
tial for radical versus partial nephrectomy. Improved
understanding of patient anatomy and pathology has
also been demonstrated for training with 3D‑printed
models of the pelvicalyceal system before percutaneous
nephrolithotripsy 7. In this study including five patients,
identification of the anterior calyx and the posterior
calices by residents improved by 52% (P = 0.018) and
76% (P = 0.009), respectively, when using models com-
pared with when using CT alone. Identification of cor-
rect stone location improved by 28% (P = 0.035) and
determination of optimal calyceal entry improved by
64% (P = 0.020).
3D‑printed models of renal anatomy also provide a
platform for patient education (FIG. 2). The increasing
complexity of urological procedures complicates educa-
tion of patients regarding pertinent details of their dis-
ease and intervention options. In a study including seven
patients, when compared with review of CT images
alone, 3D models substantially increased patient under-
standing of renal physiology (16.07%), anatomy (50%),
disease and tumour characteristics (39.3%), and, most
importantly, surgical procedures (44.6%) on the basis
of Likert scales33. Increased use of 3D constructs could
improve overall patient satisfaction and the process of
obtaining informed consent, providing a new approach
to ensure that patients truly understand the risks and
benefits of the urological procedures they are electing
to undergo.
Personalized 3D‑printed models with both realistic
anatomy and texture derived from imaging could lead
to a major paradigm shift in the way we plan surgeries,
train medical students and surgical trainees, and edu-
cate patients. The cost of the models is currently the pri-
mary barrier to the implementation of this technology.
Creation of kidney-sized models using current technol-
ogy costs around $150–500. However, these costs are
predominantly incurred by the capital cost of the print-
ers and software themselves, and once these costs have
been recouped, the per unit cost of a patient-specific 3D
model is only $10–30 (REFS 34,35). In clinical practice,
3D models printed according to a CT or MRI scan will
be useful to plan the surgical approach, enabling physi-
cians to use the construct as a visual aid in discussions
with the patient and then use that same model in the
simulation laboratory to practise the procedure and
educate medical students and other trainees.
3D printing of inorganic prosthetics and medical
devices. 3D printing enables the on‑demand generation
of medical devices, implants, and prosthetics that are
unique to a patient. This ability is in sharp contrast to
the current paradigm of using devices that are a rough
approximation of patient anatomy in standardized sizes.
In other medical fields, such as orthopaedic surgery,
neurosurgery, and maxillofacial surgery, the level of
precision and customization offered by 3D printing has
been effectively utilized. A variety of prosthetic implants
have been manufactured with 3D printing, including zir-
conium dental implants36, hydroxyapatite–­polyamide
maxillofacial prosthetics37, and moulds for customized
auricular prostheses38. In addition, surgical devices and
tools, such as titanium cutting guides4 and acrylate drill
guides for lumbar pedicle screw placement 39, have been
personalized using 3D printing. These disciplines have
been successful in making extensive clinical use of 3D
printing of implants and surgical devices because they
require solid devices, such as drill guides and polymer-­
based solid implants, that can be fabricated with a high
degree of geometric precision and personalization.
In urology and other disciplines, clinicians predomi-
nantly operate on soft tissues, and implementation of
this aspect of 3D printing is still in its infancy, as the
generation of soft tissue prosthetics and implants

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a b extravasation of contrast, and proper placement was

Figure 2 | 3D‑printed models for training and education. 3D printing enables the
Nature Reviews | Urology
creation of models with unique features of a patient’s anatomy, such as aberrant
vasculature and specific tumour dimensions, which can be useful in surgical planning,
in training residents and students, and in educating patients about complicated
conditions and procedures. a | A T2‑weighted MRI of the prostate shows a prostate
tumour (red outline), which was modelled as a 3D‑printed object. In the model, the
prostate itself is clear, the tumour is red, and the neurovascular bundles are yellow.
b | A coronal CT scan shows a left-sided renal tumour. A 3D‑printed model of the kidney
including the tumour, as well as the main vasculature, was fabricated, enabling realistic
appreciation of the tumour location and dimensions. Part a is adapted with permission
from REF. 31, Elsevier. Part b is adapted with permission from REF. 33, Springer.
often requires a level of tissue engineering that is cur-
rently an active area of research but has not yet entered
widespread medical practice.
One potential application of 3D printing that is
being investigated is the generation of antireflux ure-
teral stents. One team of researchers sought to take
advantage of 3D printing’s rapid prototyping, effective
miniaturization, and high level of precision and repro-
ducibility to generate one-way valves for ureteral stents
to reduce retrograde flow of urine40. The team developed
antireflux stents that showed great promise in in vitro
testing for the prevention of vesicoureteral–renal reflux:
retrograde flow decreased 28‑fold in comparison with a
traditional double J stent at normal maximum bladder
pressure of 50 cm H2O while maintaining an adequate
forward flow at a physiological anterograde pressure of
15 cm H2O. The valves for these stents measured only
2.8 mm in diameter, closely conforming to the size of
the 7F stent to which they were applied40. Furthermore,
traditional ureteral stents fabricated by 3D printing have
been successfully used in a porcine model41. Collecting
system integrity was maintained, which was demon-
strated by retrograde ureteropyelogram, showing no
confirmed with cystoscopy distally and dissection of
the renal pelvis proximally. Trocars for laparoscopic
surgery have also been manufactured by 3D printing to
test the utility of printed surgical equipment to reduce
waste and solve potential issues of instruments not being
available when needed41. These instruments have been
successfully used in animal models, and all instruments
effectively maintained pneumoperitoneum at 15 mmHg
and tolerated the passage of laparoscopic instruments,
albeit, with modest increases in superficial tissue defects
(mean defect length was 14.3 mm for 3D‑printed trocars
versus 12.1 mm for standard Ethicon trocars (P < 0.001)).
These constructs did function effectively, but printing
of four trocars using the stereolithography technique
required ~6 hours, bringing into question the time
efficacy of such projects41.
These initial efforts to generate surgical instruments
and implants for urological procedures demonstrate the
immense potential that 3D printing has for the specialty.
When working in the pelvis, finding the appropriate
instruments for and operating in small enclosed spaces
are consistent restrictions for urologists. The advent
of robotic surgical systems and increasingly advanced
cystoscopes and ureteroscopes assist in alleviating these
problems. Undoubtedly, a demand exists for personal-
ized, miniaturized surgical instruments, devices, and
implants engineered with an increased level of precision,
which 3D printing is uniquely poised to fulfil. In addi-
tion, 3D printing has the benefit of self-sterilization. The
temperature applied in 3D printing can generate sterile
constructs from a nonsterile feedstock of thermo­plastic,
obviating the need for further treatment after fabrica-
tion42,43. This characteristic can be especially useful for
situations in which medical practitioners might not
have access to a full array of disposables. For example,
in battlefield hospitals, sterile medical constructs could
be printed directly in the operating room, reducing the
expense of transport and maintenance.
In the future, a number of other devices could be
further customized through 3D printing. Patients who
require chronic intermittent catheterization sometimes
try several different catheter types and remain un­­satisfied;
hence, urethral catheters fabricated by 3D printing or
with 3D‑printed moulds that more accurately conform
to individual anatomy, such as prostate middle lobe
size and bladder contour, could be useful to reduce
trauma and discomfort. Customization with 3D print-
ing might also be useful for urethral slings, enabling the
generation of devices that more accurately fit a patient’s
anatomy, possibly decreasing the amount of mesh needed
for these devices. Finally, prosthetic devices, such as arti-
ficial urethral sphincters and penile prostheses, might
also be improved by customization through 3D printing.
3D printing in bioengineering. 3D printing will poten-
tially be highly valuable in the creation of synthetic
urological devices, but perhaps the most useful future
application will be in the printing of biologically active
materials. During the past 30 years, solid organ transplan-
tation has become one of the most successful surgeries

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to increase patient survival and improve quality of life.
However, the availability of suitable transplant organs
does not match the demand, and hundreds of thousands
of patients remain on donor waiting lists, with >93,000
people on the US renal transplant list alone44. 3D printing
applied to regenerative medicine is termed bioprinting
and is a methodology that might offer solutions to organ
shortage across the medical spectrum.
Traditional systems for bioprinting have operated
on an inorganic scaffold using biological substrates. In
these techniques, naturally derived polymers, such as
collagen, chitosan, or alginate44,45, or synthetic polymers,
such as polyethylene glycol46, poly(ε‑caprolactone), or
poly(lactide-co‑caprolactone)47, are deposited using one
of the aforementioned printing technologies to gener-
ate complex objects. These materials constitute the 3D
structural construct onto which the functional cells of
the target organ are then printed in a second overlying
layer (FIG. 3). After transplantation, the scaffold should
eventually degrade and be replaced by extracellular
matrix proteins produced by the functional cells. The
extent and difficulty with which these functional cells
are incorporated into the scaffold largely depends on the
level of tissue complexity.
Tissues can be ranked by four levels of complexity.
Although all organs are complex, the least complex are
flat 2D organs, such as skin. Such organs have already
been successfully fabricated in the experimental setting
and are in ongoing clinical trials for the management
of burn wounds48. Hollow tubes, such as urethras and
blood vessels, represent the second level of complex-
ity, as their architecture is more difficult to recreate.
Nonprinted constructs of these organs have been suc-
cessfully used in the clinics. In one study from 2011,
tissue-engineered urethras were established in five boys
with urethral defects by implanting cell-seeded tubular
scaffolds. The patients were monitored for up to 6 years,
showing long-term patency and functionality 49. These
studies used traditional manual pipetting techniques,
but newer studies have demonstrated that 3D printing
can replace these techniques and reduce production time
Figure 3 | 3D printing of a kidneyNature
scaffold. A hollow,
Reviews | Urology
cell-free collagen kidney scaffold is created by extrusion
printing.  Subsequently, functional cells will be layered
over this scaffold in the hollow space. Following
transplantation, the scaffold should eventually degrade
and be replaced by extracellular matrix proteins produced
by the functional cells.
and variability between constructs. In one study from
2017, a urethral construct was printed using an organic
polymer with smooth muscle and urothelial cells. The
cells maintained 80% viability at 7 days after printing 47.
Hollow, nontubular organs, such as the bladder and
vagina, represent the next level of organ complexity.
They are architecturally unique and have more exten-
sive interactions with other organs. These organs have
not yet been 3D printed, but bioengineered constructs
have been successfully studied in the clinical setting. In
one pilot study from 2014, neovaginas created from an
organic polymer scaffold seeded with native cells were
implanted into four patients with congenital vaginal
aplasia50. All constructs remain functional and viable
after 8 years of follow-up monitoring. Finally, solid
organs such as the kidney are the most difficult organs
to produce. These organs comprise many more cells
per cm than any of the other organ types, and main-
taining adequate nutrition through vascularization is
still a challenge in bio­engineering. Solid organs, such as
kidneys, are being created experimentally using various
bio­engineering techniques with and without 3D printing
but are not yet ready for clinical application10.
Engineered organs that have been implanted into
patients to date have been manufactured by hand, but
the goal is to create organs for clinical application using
bioprinting strategies to enable mass production and
reduce variability between units. Owing to the limita-
tions of the different printing techniques, achieving the
required structural and biological construct integrity
using 3D printers has proved difficult. However, a new
hybrid system called the integrated tissue–organ printer
(ITOP) has been developed to overcome these structural
issues51. This system utilizes multi-dispensing modules to
deliver various cell types and polymers in a single con-
struct rather than the commonly used two-step scaffold–
organic substrate approach. By depositing cell-containing
hydrogels together with synthetic biodegradable poly-
mers that impart mechanical strength, this system over-
comes previous limitations on the size, shape, structural
integrity, and ability for vascularization of bioprinted tis-
sue constructs. ITOP also enables printing of multiple cell
types to replicate the cell types of the target neo-­organ.
This system has demonstrated proof of concept in the
printing of ear cartilage, bone, and smooth muscle tis-
sue, and its utility in constructing more complex tissue,
including renal tissue, is currently being studied.
3D bioengineering is still in its infancy, but findings
to date are promising. Most studies created constructs
by hand pipetting, but they highlight the potential use of
3D printing. The bioprinting technology provides four
major advantages over existing technologies. In compar-
ison with manual pipetting, bioprinting enables fabrica-
tion of more precise constructs, as cells can be deposited
more accurately. Reproducibility is improved, as the
printing programme creates models with the same pro-
duction parameters. Bioprinting also enables large-scale
production owing to the automation provided by addi-
tive manufacturing. Finally, bioprinting has the poten-
tial to reduce production costs, potentially increasing
access to bioengineered organs in general health care.

NATURE REVIEWS | UROLOGY ADVANCE ONLINE PUBLICATION | 7

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Future perspectives
3D printing of medical constructs is likely to have
widespread application in the future. In the past, 3D
printers were prohibitively expensive, but modern ink-
jet printers can now be purchased for $300, and even
extrusion printers can be purchased for <$2,000 (com-
pared with several tens of thousands of dollars in the
past). 3D‑printed medical constructs can be inorganic
or organic objects. The technology is already available to
apply inorganic constructs in clinical practice. Various
vendors have developed commercially available printers
and software that can convert CT and MRI data into
3D models, and the technology is already in use for
patient and physician education. These applications are
currently predominantly limited to academic settings,
but small-scale 3D printers can be purchased for <$500,
making this technology accessible across the clinical
practice spectrum.
Research of 3D printing of organic constructs is
progressing, but the technology and created constructs
have not yet reached the clinic. Particularly for com-
plex organs, technical aspects of both printer and bio-
ink need to be advanced further. Although researchers
have had some success with various constructs and
tissue complexities, the field is still at an early stage of
develop­ment for all medical applications, including
urological use. Technological challenges of 3D printing
include the need for increased resolution and speed, as
well as incompatibility with biologically relevant mate-
rials. Much work remains, but further advances with
bio­engineered organs will enable clinicians to provide
patients with personalized, functional constructs that
can be used for surgical reconstruction.
Conclusions
3D‑printed construct creation has considerably
advanced since the milling machines used to generate
surgical models in the early 1980s. These original con-
structs were simple structural supports, but modern
material technology has enabled the creation of dynamic
objects that can mimic real tissues. Four general tech-
niques are used for 3D printing (inkjet printing, extru-
sion printing, laser sintering, and stereolithography),
each with specific advantages and disadvantages. These
techniques are invaluable as they enable the creation of
not only on‑demand, patient-specific prostheses but
also teaching models that can inform both patients and
practitioners about the complexities and unique aspects
of a specific surgery. Perhaps the most important future
application of 3D printing will be the creation of organic
constructs. Such constructs might enable urologists to
replicate and replace diseased or lost organs with func-
tional equivalents and might improve the quality of life
for patients.

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Author contributions
All authors researched data for the article, made substantial
contributions to discussion of the article content, wrote, and
reviewed and/or edited the manuscript before submission.
Competing interests statement
The authors declare no competing interests.
Publisher’s note
Springer Nature remains neutral with regard to jurisdic-
tional claims in published maps and institutional
affiliations.

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