2019 The Current Versatility of Polyurethane 3D Printing For Biomedical Applications

Tissue Engineering
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© Mary Ann Liebert, Inc.

DOI: 10.1089/ten.TEB.2019.0224
1
The current versatility of polyurethane 3D‐printing for biomedical
applications
This paper has been peer‐reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Griffin Michelle MBChB MRes MSc MRCS PhD1‐3, Castro Nathan PhD4, Bas Omar PhD4,
Saifzadeh Siamak4, Butler Peter MD FRCS (Plast)4, Dietmar Hutmacher PhD4
1. Charles Wolfson Center for Reconstructive Surgery, Royal Free Hospital, London,
United Kingdom, NW32AW
The current versatility of polyurethane 3D‐printing for biomedical applications (DOI: 10.1089/ten.TEB.2019.0224)
2. Division of Surgery & Interventional Science, University College London, London,
Downloaded by Karolinska Institutet University Library from www.liebertpub.com at 02/27/20. For personal use only.
United Kingdom, NW32AW, 02077940500.
3. Department of Plastic Surgery, Royal Free Hospital, London, United Kingdom,
NW32AW, 02077940500.
4. Institute of Health and Biomedical Innovation, Queensland University of
Technology, Brisbane, Queensland, Australia, 313, GPO Box 2434, Brisbane QLD
4001, Phone: 3138 6000, Fax: 3138 6030.
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Corresponding Author;
Dr Michelle Griffin: 12michellegriffin@gmail.com
Division of Surgery & Interventional Science, University College London, London, United
Kingdom, NW32AW, 02077940500.
Authors Details:
1) Castro Nathan PhD, nathan.castro@qut.edu.au, Institute of Health and Biomedical
Innovation, Queensland University of Technology, Brisbane, Queensland, Australia,
313, GPO Box 2434, Brisbane QLD 4001, Phone: 3138 6000, Fax: 3138 6030
2) Bas Omar PhD, o.bas@qut.edu.au, Institute of Health and Biomedical Innovation,
Queensland University of Technology, Brisbane, Queensland, Australia, 313, GPO
Box 2434, Brisbane QLD 4001, Phone: 3138 6000, Fax: 3138 6030
3) Siamak Saifzadeh, siamak.saifzadeh@qut.edu.au, Institute of Health and
Biomedical Innovation, Queensland University of Technology, Brisbane,
Queensland, Australia, 313, GPO Box 2434, Brisbane QLD 4001, Phone: 3138 6000,
Fax: 3138 6030

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NW32AW, 02077940500.
University College London, London, United Kingdom, NW32AW, 02077940500.
Interventional Science, University College London, London, United Kingdom,

6. Dietmar Hutmacher, dietmar.hutmacher@qut.edu.au, Division of Surgery &
5. Peter Butler, peter.butler1@nhs.net, Division of Surgery & Interventional Science,
2
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Abstract
Reconstructive surgery aims to restore tissue defects by replacing them with similar
autologous tissue to achieve good clinical outcomes. However, often the defect is too large
or the tissue available is limited requiring synthetic materials to restore the anatomical
shape and partial function. The utllisation of three‐dimensional (3D)‐printing allows for the
manufacture of implants with complex geometries and internal architectures that more
closely matches the required clinical needs. Synthetic polymers offer certain advantages
over natural polymers as biomedical materials due to their ability to more closely mimic
the mechanical and chemical properties of the native tissue. Synthetic polymer materials
such as Poly(lactic Acid) (PLA), Acrylonitrile butadiene styrene (ABS) are easily 3D‐printed
to generate 3D objects due to their flexibility in their chemical and mechanical properties
and physical form. Polyurethanes are widely used as short‐ and long‐term implantable
medical devices due to their good mechanical properties, biocompatibility and
haemocompatibility. This article provides an overview on the advancement 3D printable
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polyurethane‐based materials for biomedical applications. A summary of the chemical

structure and synthesis of polyurethanes is provided to explain how polyurethanes may be
processed into medical devices using additive manufacturing techniques. Currently
polyurethanes are being explored by several 3D‐printing approaches including fused
filament fabrication (FFF), bioplotting and sterolithography (SLA) to fabricate complex
implants with precise patterns and shape with fine resolution. Polyurethane scaffolds
using 3D‐printing have shown good cell viability and tissue integration in vivo. The
important limitations of polyurethane printing are identified to stimulate future research.
Polyurethanes offer a biocompatible synthetic polymeric material that can be 3D‐printed
to manufacture implants, which are tailored to meet specific anatomical, mechanical and
biological requirements for biomedical applications.
Key Words
Polyurethane, 3D‐printing, additive manufacturing, synthetic polymer, fused deposition

modeling, stereolithography

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Impact Summary
Polyurethane materials have been utilized for a number of biomedical applications due to
their good biocompatibility versatile properties. With advancements in 3D‐printing

technologies, processing of polyurethanes to more closely mimic the native extracellular
matrix of human tissues and organs and provide enhanced tissue engineering applications
can be achieved. This review highlights how various 3D‐printing processes offers a
platform by which to manufacture implants with precise control over internal and external
structure to create tissues with the desired outcomes.

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1. Introduction
The aim of reconstructive surgery is to enable the body to heal and allow for restoration of
tissue form and function.1 Reconstructive surgery is constantly evolving developing
alternative strategies to repair damaged tissues. 2 Bone, cartilage and soft tissue defects
can be restored using local tissue or tissues from elsewhere in the body in the form of free‐
flaps, where a blood supply is also delivered to the defect site.2 However, when the
available tissue is insufficient to repair the defect, the reconstructive surgeon will need to
rely on incorporating synthetic materials to provide a solution.2 Biocompatible materials
are currently being explored, to provide a role in the manufacturing of functional
replacements of damaged tissues and organs.3 Such scaffolds aim to provide a platform for
tissue repair or regeneration to occur.3 The scaffolds can remain for the life‐time of the
patient or degrade and allow for new tissue formation depending on the clinical scenario.3
Cells have shown to react to subtle physical, chemical and mechanical cues in their
environment.4 Considering such behaviour, scaffolds are commonly fabricated to have
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specific pore sizes and shapes to create structures that allow for tissue ingrowth from the
host tissue.5 The presence of pore and architectures in biodegradable materials for the
consideration of tissue‐engineering applications provides cell migration and tissue
ingrowth to cause eventual replacement of the scaffolds.5 In non‐biodegradable scaffolds,
ingrowth is useful to provide attachment and anchorage to the surrounding tissue and
prevent migration of the implant.5
A number of synthetic and natural polymers have been studied and proposed as
scaffolds.6 Natural polymers including polysaccharides and proteins are frequently
investigated due to their biocompatibility, minimal toxicity and low costs.6 Furthermore,
natural polymers have shown to direct cell responses for tissue engineering applications.6
However, their mechanical properties do not always match the native tissue and their
biodegradability can be unpredictable.6 On the other hand synthetic polymers can offer
versatility in their physical and mechanical properties.7 Several synthetic polyester‐based
polymers have already been approved by the FDA including poly(glycolic acid) (PGA),
poly(lactic acid) (PLA) and poly(ε‐caprolactone) PCL. Another group of synthetic polymers
are the polyurethanes.7 Polyurethanes are among the most popular synthetic biomedical
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polymers due their biocompatibility, ease to modify their chemical properties and
mechanical properties.8 Polyurethanes present a class of polymers used in the medical,
industrial and automotive fields.9 Polyurethanes are currently used for several medical
applications including tubings10, dressings11, catheters12‐13, surgical drains14, cardiovascular
devices15‐17 and device coatings for devices including breast implants18. They are highly
resistant to degradation by water, oil and solvents making them a frequently used plastic
material.19‐20 As coatings polyurethanes provide excellent adhesion, abrasion resistance
and weather resistance for industrial purposes.19‐20
Polyurethane scaffolds can be fabricated using multiple techniques including

solvent casting/particle leaching, gas foaming and freeze drying to obtain 3D‐scaffolds with
a porous architecture.9 However, they are often limited by production of thin scaffolds or
the inability to create uniform pore patterns.9 However, 3D‐printing is an alternative
fabrication technique that allows for the precise control over shape and dimensions of the
scaffolds.21 Furthermore, 3D‐printing, also referred to as additive manufacturing, rapid
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prototyping or solid freeform, is a process where an object is created from a 3D model
data layer‐by layer.22 Pore size, shape and overall dimensions can be tailored to create the
desired response in the host tissue.22 Such control of the scaffold, allows the
vascularization, oxygenation and the nutrient supply to be optimised to ensure a good
outcomes once implanted in the clinical setting.22 The ability to control architecture allows
is valuable for biomedical field as it allows for the manufacture of bespoke patient specific
implants or repeatability and reproducibility of a number of implants.22 Despite the wide
applicability and versatility of 3D‐printed polyurethanes for biomedical applications, a
review of the current status of polyurethanes for biomedical applications has not been
performed. This review aims to introduce the polyurethane polymer family, demonstrates
it applicability as a 3D‐printing biomaterial, and provide an insight into how the material
can be further utilised in 3D‐printing for biomedical applications.
2. Background to Polyurethanes
The first polyurethanes were developed in the 1950s after World War I by Bayer and
demonstrated to be a very versatile materials used in both domestic and industrial
applications.23 Polyurethanes are a family of polymers in which the repeating unit contains
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a urethane moiety (Figure 1A).24,25 Polyurethanes are created by the reaction of
diisocyanate, oligodiol (i.e macrodiol or polyol and a chain extender (diol or diamine).24‐27
Polyurethane polymers are considered multi‐block polymers with the isocyanate being
either aromatic or aliphatic.19,23,24 Aromatic polyurethanes have a higher reactivity and
better mechanical properties than aliphatic isocyanates.19,23,24 Common aromatic
isocyanates are 2,4‐toluene diisocyanate (TDI), 4,4‐diphenylmethane diisocyanate (MDI),
and 1,5‐naphthalene diisocyanate. Aliphatic isocyantes are considered less toxic and more
stable to light.19,23,24,27 The oligodiols are normally polyether, polyester or polycarbonate
based.24‐27 Polycarbonate‐based polyurethanes are more durable, with good mechanical

properties and hydrolytic resistance. The chain extenders are low molecular weight diols
or diamines, normally below 400Da.24,25,27 Segmented polyurethanes consist of a soft and
hard segment. The soft segment is the oligodiol and the hard segment is built from the
isocyanate and the chain extender.24‐27 The separation of the hard and soft segment,
termed the microphase separation provides the elasticity to the polyurethane and
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determines its mechanical properties, thermal stability and hydrolytic resistance.24‐27 The

variation of these segments results in the varying elastic and tensile properties of different
polyurethanes.24‐27 The biocompatibility of various polyurethanes has been extensively
evaluated for in vitro and in vivo applications from long lasting polyurethane devices such
as vascular catheters to biodegradable scaffolds for tissue engineering applications.27,28
Multiple cell types have been used to assess the toxicology of polyurethane materials in
vitro including fibroblasts, endothelial cells, osteoblasts and adult stem cells demonstrating
good adhesion, proliferation and short‐term bio stability in vitro.29 Early studies in vivo
studies have showed the application of polyurethanes as regenerative scaffolds for bone
tissue engineering and confirmed biocompatibility and haemocompatibility.28,30‐31
3. Synthesis of Polyurethanes
Polyurethanes are synthesized in a one or two‐stage process.26 In a one‐stage process the
isocyanates, oligodiols and chain extenders are reacted simultaneously (Figure 1B).26 The
two‐stage process involves the creation of a pre‐polymer before further chain extension,
to create a polyurethane with more uniform structure (Figure 1B).26,33 Polyurethanes can
be classified as thermosetting or thermoplastic.33‐34 Thermosetting polyurethane polymers
is a pre‐polymer in a viscous liquid state that changes irreversibly into an insoluble
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polymer network due to the chemical bonds formed by the action of heat, radiation, or
with the mixture of a catalyst.34 Thermoplastic polyurethanes are polymers which can be
melted and reformed and are highly elastic and flexible. 33‐34
4. Biomedical Polyurethanes
Polyurethanes for biomedical applications should have good biocompatibility and physical
properties mimicking the tissue it is replacing.35 Polyurethanes have been found to be
susceptible to degradation. The chemical composition and topology alter the degradation
properties. Regularity of the synthetic polymer chain, creates crystalline regions, limiting
the polymer chains to degradative agents.35
The first biomedical polyurethanes were poly (ether urethanes) based, which
demonstrated good mechanical properties, biocompatibility and resisted hydrolytic
degradation in vitro.36 However, polyether polyurethanes, showed to degrade significantly
faster under enzymatic attack and oxidative environments in vivo.37 The polyurethanes
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were also susceptible to cracking at points of high stress after long‐term implantation.37
Foreign body giant cells were also found to adhere to polyurethane materials causing free
radical attack.38 In conclusion, polyether‐based polyurethanes were considered not
suitable for long‐term implantation.39 To overcome such problems polycarbonate‐based
polyurethanes were synthesized which exhibited greater tolerance to hydrolytic and
oxidative resistance when compared to poly (ether urethane) polymers. The excellent
biostability, biocompatibility, haemocompatibility and mechanical properties of such
materials prompted their adoption as biomedical materials.35,39 Biodegradable
polyurethanes are also available by introducing biodegradable content into the
backbone.40‐41 Biodegradable materials including cellulose, alginate and starch can be
incorporated into soft segments of the polyurethane.40‐42 Synthetic biodegradable
polymers can also be blended with polyurethane polymers including polylactides and
polycaprolactone42 where degradation of the polyurethane ensues by hydrolysis of the
ester soft and hard segment bond.24,35 The soft segments often degrade faster than the
soft segment due their lower accessibility.35 Several factors determine the degree of
biodegradability of the polyurethanes in vivo including hydrolysis, environmental stress
cracking, oxidation, enzymatic degradation and oxidation leading to excretion via the liver
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and or/kidney.35 It has also been advised to avoid aromatic isocyanates because during
hydrolysis toxic amines can be formed.35
5. Polyurethanes Fabricated using 3D printing
The goal of tissue engineering is to closely resemble the native extracellular matrix (ECM)
to guide cells towards new tissue with appropriate function.43 Additive manufacturing can
fabricate scaffolds with specified dimensions and geometry.44 Thus, 3D‐printing is a
controlled process that provides flexibility and reproducibility to create high performance
products.44 There are several types of 3D printing including fused filament fabrication
(FFF), low temperature deposition, stereolithography (SLA), selective laser sintering (SLS)
and bioplotting. Each of the techniques has advantages and disadvantages (Table 1).42‐45
Synthetic polymers can be printed via several of these methods, with the fabrication
technique dependent on the starting material, requirement of processing speed and
resolution, cost and performance requirements of the final product.45 Currently,
polyurethanes have been explored with FFF, SLA and bioplotting 3D‐printing techniques.
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5.1 Fused Filament Fabrication (FFF) of Polyurethanes
Fused filament fabrication (FFF) is the most commonly utilised and cost‐effective additive
manufacturing approach.46 It is a filament‐based approach, where the filament is fed into a
heating nozzle to be heated, melted and then extruded layer‐by layer to create a solid
object.46 FFF is widely used in the tissue‐engineering field due to the lower price of the
printers, ease of processing and minimal training and safety requirements compared to
other forms of 3D fabrication.46 Thermoplastic polymers such as polycarbonate (PC), ABS
and PLA are printed using this technique as they have low melting points.46 The quality of
the printed structure is dependent on the optimization of the printing parameters
including, layer thickness, printing orientation, printing speed and the physical parameters
of the printing nozzle head.46 To print polyurethane via FFF printing the material needs to
be in filament form.45 The most common filament forms for 3D‐printing using FFF include
1.75 mm and 3.0 mm.47 There are several commercial thermoplastic polyurethanes
filaments available labelled as the ‘flexible range’ (Table 2).47 Printing such polyurethane
filaments by FFF is not without its challenges, needing careful optimization and adjustment
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in printing parameters.47 Thermoplastic polyurethane becomes molten at high
temperatures, thus can be easily processed using FFF printing.
Several flexible filaments have been printed using FFF‐printing. Castro et al showed a
commercially available thermoplastic polyurethane‐based composite filament (Gel‐Lay)
could be printed via a FFF printer to create porous structures (Figure 2).48 The filament
contains the water‐soluble polymer polyvinyl alcohol (PVA) polymer within the filament in
addition to polyurethane, which when dissolves, rendering the rigid scaffold more porous
and elastic.48 To make the scaffolds more bioactive the flexible, they were incubated in
simulated body fluid (SBF). This induced mineral nucleation resulting in apatite formation
upon the material’s surface; enhancing cell behavior.48 Hence, this study also illustrates
the advantageous ability of implementing surface treatments of polyurethanes to induce
desired cell responses.48
Porolay, lay‐fomm40 and layformm60 have also been investigated as tracheal scaffolds
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along with a polyester (polycaprolactone) polyol based (TPU‐80) and a polyether polyol
based (TPU‐0) TPU using FFF printing.49 The novel formulations were extruded into
filaments.49 All polymers were able to create 3D‐printed tubular structures, with flexibility
in design of the infill density and pattern.47 The two formulations were able to printed
together to mimic the structural and mechanical biomimicry of an adult trachea.47 Dual
printing of the polyurethanes enabled complete, structural biomimicry of the
heterogenous tissue construct, with TPU‐90 mimicking the cartilage rings and the
trachealis muscle being printed with the TPU 80.49
Extrusion of polyurethane using FFF printing also allows thermoplastic polyurethanes to be
blended with other materials, forming filaments of multiple materials, which could offer
greater specificity and applicability in the medical field. Chen et al evaluated 3D‐printing
polyurethane/poly (lactic acid (PLA)/grapheme oxide (GO) nanocomposites using FFF
printing (Figure 3A‐B). PLA, is frequently used in biomedical applications due to high
biocompatibility and biodegradability. It is also mechanically strong and rigid.50 PLA was
blended with polyurethane for to improve the overall mechanical strength and impact
resistance.50 Modifications of the polyurethane and PLA weight ratios created polymers
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which can be tailored to meet different applications requirements. Graphene, a single
layer of sp2 hybridized carbon atoms, which has excellent thermal, electrical and
mechanical properties was also incorporated into the filament.50 Solutions containing
polyurethane, GO and PLA were formed, then precipitated in alcohol, vacuum dried then
extruded by a mini‐extruder to create a nanocomposite filament. The addition of the
graphene improved the mechanical and thermal properties of the polymer. Printing
orientation was observed to influence the mechanical properties. As well as ease of
printing, the nanocomposites demonstrated good biocompatibility with NIH3T3 cells,

showing growth, cell spreading and proliferation.50
One of the concerns with FFF printing is the physical properties of the printed object after
it has been extruded.51 Miller et al evaluated the fatigue properties of both FFF
polyurethane by physical crosslinking to photocuring chemically cross‐linked, elastomeric
polyurethane printed via continuous liquid interface production (CLIP). Both polyurethanes
were tolerate of 3D geometrical features compared to PEEK and titanium.51 Interestingly,
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the polymers performed similarly in tensile fatigue despite the presence of chemical
crosslinks and vastly different printing methods.51
Medical grade polyurethanes have also been explored using FFF‐printing to create
scaffolds for biomedical applications. Xiao et al utilized FFF technology to print the medical
grade thermoplastic polyurethane, Tecoflex LM‐95A Lubrizol.52 The material was an
aliphatic polyether‐based polyurethane, and a semi‐crystal polymer.52 The thermoplastic
polyurethane was first processed into a 1.75 mm filament, using a single screw extruder
and then fed into a desktop FFF printer (MakerPi M14).52 The effects of orientation angle
and extrusion temperature on the tensile properties of the 3D‐printing thermoplastic
polyurethane were explored.52 Printing with 45° and at 215°C provided the optimal
printing parameters, with small internal stress and good thermal bonding.52
FFF also allow the manufacture of scaffolds to allow for indirect printing of polyurethanes.
Indirect 3D‐printing is an approach whereby the final scaffolds is printed, as a sacrificial
structure, that is later removed after casting the polymer being investigated in and around
it. This allows for polymers such as polyurethanes to be manufactured into geometries
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that may not suitable using the direct 3D‐printing approach. Hernandez‐Cordova et al
utilized this technique to fabricate scaffold for cardiac tissue engineering using their
biodegradable polycaprolactone based polyurethane urea copolymer (Figure 3C‐D).53 PVA
was selected as the material for the sacrificial mould to its biodegradability,
biocompatibility and high‐water solubility. The 3D‐printing of dissolvable PVA porogen
scaffolds with different sized pores was printed using an FFF printer (Makerbot). The soft
polyurethane urea scaffold was then poured over the PVA mould and injected using a
nitrogen gas. The PVA porogen was completely removed by placing the scaffold in distilled
water over a 3‐day period.
Lastly, FFF printing has shown the ability to allow for the printing of combing
polyurethanes to enhance the properties of the material. Guney et al demonstrated that
polyurethanes based on poly(ɛ‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ɛ‐
caprolactone) (PCL‐b‐PEG‐b‐PCL) triblock copolymers and hexamethylene diisocyanate
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(HDI) could allow for the varying of mechanical properties to print scaffolds with higher
fracture toughness (Figure 3E‐H).54
5.2 Bioplotting of Polyurethanes
In a similar approach to FFF printing a 3D object can be designed and fabricated using
bioplotting techniques.55 In this approach, the object is also created using a layer‐by layer
approach as in FDM printing but uses bio‐inks instead of filaments. The bioplotter
dispenses bioinks onto a suitable substrate of choice using a cartridge or syringe.
Microextrusion is one bioprinting method that can print polymers, cell spheroids and many
hydrogels.45‐46 There are two main dispensing systems used to extrude the biomaterials
including mechanical and pneumatic.55‐56 Polyurethanes have been evaluated in different
bioplotting systems to create 3D scaffolds.
The main advantage of using bioplotting is the ability to create a complex structure
mimicking the structure of native tissue by using multiple synthetic biomaterials and cell
types. Merceron et al demonstrated tbe ability to create a muscle‐tendon unit construct
for musculoskeletal applications.56 Thermoplastic polyurethane was co‐printed with a cell‐
laden hydrogel‐based bioink for muscle elasticity development on one side, while PCL was
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co‐printed with a cell‐laden hydrogel‐based bioink for stiffness and tendon development
on the other side.54 The constructs showed viability up to day 7 with suitable mechanical
properties for muscle‐tendon engineering.57
Medical grade thermoplastic polyurethane has also been successfully printed using
bioplotting to create 3D‐printing tracheal scaffolds.57 A favorable element of the 3D‐
printing process is that the object can have different layers of densities, creating implants
that more closely mimic the natural design strategy of tissues and organs. The trachea was
designed with two parts demonstrating different internal patterns. The outer part was
non‐porous to create an air‐tightness and allow flow up and down the trachea. On other
hand the inner part was porous to allow for tissue integration and remodeling. The
tracheal scaffolds were printed with 200 μm printing beams and 400 μm pitch (distance
between centerlines of two neighbouring beams) for the porous layer. The thermoplastic
polyurethane was dissolved in chloroform (40% w/v) and then loaded into the metal
printing syringe for printing via a 200 nm metal nozzle at room temperature. The scaffolds
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showed a Young’s modulus of 2.81 ±0.58MPa and the native trachea cartilage was found
to have a modulus of 0.20±0.07MPa. The scaffolds were implanted into a 1.0 x 0.7 cm3
tracheal defect in rabbits, showing patency and maintenance of mechanical properties
after 16 weeks with ingrowth of connective tissue at 4 weeks.
Tissue engineering aims to optimize the functionality of the final tissue product, providing
appropriate cues to create the desired cell behavior.53 Mechanical stimuli including
compressive and tensile strain are known to influence cellular behaviour.59 Proving such
cues through bioreactors can enhance bone and cartilage formation by cells. However,
these are costly and have limited scope. As an alternative, materials that possess an
intrinsic mechanical stimulus can be used.59 Hendrikson et al fabricated 3D shape memory
polymer (SMP) scaffolds, which are able to change their shape in time during culture,
allowing for four‐dimensional (4D) SMP scaffolds to provide tissue regeneration.59 An
aromatic shape memory polyurethane was printed via a bio‐scaffolder extrusion system
with fiber spacing of 1000nm at 90 and 45‐angle between layers. The polyurethane
meshes were then brought to 65 degrees where a temporary shape is imparted by
applying a 50% strain and fixed by cooling to 40C. The scaffolds were then cultured at 300C
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to allow cell adhesion before the temperature was restored to 370C, to release the strain
imparted to the scaffolds through the recovery of the permanent shape. When human
mesenchymal stem cells were seeded on the scaffolds in the temporary shape and the
permanent shape was recovered, cells demonstrated a greater elongation. Thus, the single
mechanical stimuli‐initiated changes in the morphology of the cells.
One of the main problems of utilizing polyurethanes is they are often dissolved in toxic
organic solvents, which need to be removed for clinical translation. This can cause
problems as the solvents may remain after production, affecting long‐term
biocompatibility for implantation. Waterborne polyurethanes are synthesized by inserting
an ionic component that transforms polyurethane to an ionomer, making it dispersible in
water.60 Studies have shown that a water based polyurethane materials can be utilized in
3D‐printing. Waterborne processes for the synthesis of biodegradable polyurethane
nanoparticles based on mixed oligodiols have been reported.6‐ Hsieh et al described the
manufacture of two thermoresponsive water based polyurethane dispersions, which
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formed a gel near 37oC without any crosslinker. Murine neural stem cells were
encapsulated in the gel and 3D printed and maintained at 370C. The 3D bioprinting of NSC
laden constructs using the thermoresponsive polyurethane ink demonstrated excellent
proliferation and differentiation and rescued the function of the impaired nervous system
in a zerbrafish embryo.60 Hsu et al also demonstrated that water polyurethane polymers
can be printed with cellulose nanofibers using a water‐soluble viscosity enhancer
polyethylene oxide (PEO). Fibroblasts were able to proliferate on the scaffolds showing
that the combination of cellulose and polyurethane may over a unique way to tune
waterborne polyurethane materials for 3D printing.61
Similarly, printed scaffolds using the aqueous dispersion of polyurethane nanoparticles
with hyaluronan as a viscosity enhancer was used for cartilage tissue engineering.62 The
polyurethane (PU) ink offers several advantages including having a tunable biodegradation
rate, high compliance and bioactivity from the HA. In addition, the scaffolds were also
functioned to release Y27632(TGF‐β3) a known chondrogenic induction factor. The
compressive moduli of the PU/HA scaffolds were found to be in the range of native
cartilage. MSCs seeded in the scaffold self assembles and underwent chondrogenesis
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effectively.59 Furthermore, transplantation of the MSC seeded PU/HA/Y27632 scaffolds in
rabbit chondral defects improved cartilage regeneration.62
Tsai et al also evaluated a waterborne polyurethane using extrusion‐based printing.63 The
study utilized waterborne polyurethane based on PCL diol and a second oliogdiol
containing amphiliphilic blocks. The water‐based dispersion of polyurethane nanoparticles
with a solid content of 25‐30% were easily mixed with cells in a sol gel state and 3D printed
in layers. The cells within the material could easily be printed layer‐by‐layer as a gel,
remaining alive and proliferating in the printed hydrogel scaffold. These studies highlight
the development of potential 3D‐polyurethane based bioinks for tissue engineering.
5.3 Inkjet Printing of Polyurethanes
Similar to daily used inkjet printers, inkjet bioprinting deposits droplets from a nozzle in a
continuous strand or single dots to create a finalized product.64 Thermal inket printers
localized heat within the nozzle, which causes the ejection of a small droplet from the
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nozzle.65 Piezolectric actutators can be used to eject droplets from the nozzle to be able to
maintain the viability of cells or bioactive factors.65 Two studies have shown the ability to
incorporate polyurethanes into ink‐jet printing. Krober et al has shown that this
technology could be used to create micro‐scale polyurethane structures including dots,
lines and pyramids.66 The structured were fabricated by printing two separate inks
successively with two print heads. One of the heads contained the isophorone dissocyante
and the other consisted of an oligomer of poly (propylene glycol), catalyst and cross‐linking
agent.66 Another study manufactured gradients within the scaffolds using inkjet printing by
using three print heads, 2‐polyols and 1‐isocyanate. The mechanical properties of the
object were tailored by controlling the composition of the three components.67
Pfister et al compared scaffolds printed via bio‐plotting to inkjet printing of aliphatic
polyurethanes.68 The commercial ZP11 Z‐corp printer was used to bond starch particles
followed by infiltration and partial crosslinking of starch with lysine ethyl ester disocyanate
to create layer‐by‐layer biodegradable scaffolds. Alternatively, the bio‐plotting process
allowed for the 3D dispensing and reactive processing of oligoetherurethanes derived from
isophorone dissocyanate, olioethylene oxide and glycerol. Both techniques created 3D
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polyurethane scaffolds, suitable for osteoblast attachment and growth. The resolution,
speeds of printing and total time required for scaffold preparation were similar between
the two modes of printing. However, the bioprinting approach allowed for the mechanical
properties to be tailored unlike the post treatment requirements of the 3D‐printed
process. Furthermore, the 3D bioplotter could fabricate scaffolds from very small
quantities in comparison to the commercial 3D‐printers which require at least 2kg of
powder.68
5.4 Stereolithography (SLA) of Polyurethanes
In SLA printing, monomers are mixed with a photo‐initiator, which enables the polymer to
be cured by an ultraviolet (UV) laser. A UV laser is controlled in a bath of photocurable
resin, which is polymerized into a 2D patterned layer. After each layer is cured, the
platform lower for another layer to be cured.69
Fewer studies have reported the use of polyurethanes for SLA printing compared to
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extrusion and FFF based systems. Shie et al demonstrated that water borne polyurethane
could be 3D printed using SLA printing to fabricate customised cartilage scaffolds (Figure
4).70 During the curing process, the water in the water‐based light cured polyurethane
resin was removed and then hydroxyethylmethacrylate to adjust the viscosity and
photoinitiators for light curing were added. When a specific proportion of the water‐based
thermoplastic polyurethane was composed, the mechanical properties mimicked articular
cartilage. The polyurethanes also supported cell growth up to 3 days. The study also
highlighted the ability to add hyaluronic acid molecules to the scaffold, an important
component of articular cartilage, providing lubrication in the joint.70 Similarly, UV curable
polyurethanes have shown to the capability to be 3D printed with other materials. Mohan
et al printed UV curable polyurethane based resin with cellulosed nanofibrils and
polyethylene glycol (PEG) and reduced graphene oxide.71 Graphene nanoplatelets have
also been 3D‐printed with polyurethane using SLA techniques. The hardness of the
photocurable PU composites increased following the addition of graphene nanoplatelets.
72

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Most polycarbonates are produced by the reaction of polyols with isocyanates. These
isocyanates are commonly derived from highly toxic phosgene compounds and can cause
toxic byproducts down‐stream. One method to avoid such products is to create
polyurethanes using ‘green chemistry’. This is using ring‐opening polymerization to
produce polymer without toxic additives, which can be applied to six membered functional
cyclic carbonates. The cyclic carbonates can then be modified with functional groups such
as methacrylate groups to impart different properties. Pyo et al demonstrated that with
green chemistry‐derived isocyante free aliphatic polyurethanes they could create

photosensitive scaffolds. The polyurethane created with amines and cyclic carbonates
functionalized with methacrylate groups could be UV crossed linked into 3D structures.
High‐resolution 3D biomimetic structures were printed, along with high cell viability on the
printed structures.73
To date only a few commercial polyurethanes have shown to be printed using the SLA
process. Bayer Demosin® have released a new flexible thermoplastic polyurethane called
Tissue Engineering
TPU 92A‐1 that is suitable for SLA printed, with good mechanical properties, durable
elasticity, high tear and abrasion resistance.74
5.5 Low Temperature Deposition of Polyurethane
Low temperature deposition printing is a recently developed manufacturing technique. It
is considered a green manufacturing technique, which can fabricate scaffolds with
controlled and inter‐connected micropores.75 It creates scaffolds in a layer‐by‐layer fashion
in a low temperature chamber, with temperatures below 0oC, with scaffolds being freeze
dried to remove the solvent.72 This technique can be utilised to incorporate growth factors
into the scaffold.75 Polyurethane materials have been successfully 3D‐printed into specific
implants using this technique.75
Gelatin and alginate hydrogels are highly investigated in bioplotting approaches due their
ability to mimic the ECM.72 However, the mechanical properties of such hydrogels are too
low to withstand the load and stresses that occur in the native setting. Low deposition 3D‐
printing can overcome this limitation and improve the mechanical properties of
hydrogels.76‐78 Low temperature deposition polyurethane printing has been successfully
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utilised in the field of vascular tissue engineering. Huang et al combined cell assembly, low
temperature deposition and cell cryopreservation techniques to fabricate a tubular
polyurethane sandwich like cell hydrogel.76 The construct demonstrated good cell viability
and the ability to preserve the 3D construct for more than a week.76
Other studies have shown that low temperature deposition printing is useful in creating
specific anatomical implants. An elastomeric polyurethane, based on polycaprolactone and
poly (ethylene glycol) was shown to be fabricated into a 3D object with an intrinsic
network of interconnect channels, printing at low temperatures (‐28oC).77 In addition, Cui
et al demonstrated that low temperature deposition polyurethane printing is useful for
preparing double‐layer polyurethane‐collagen nerve conduits for peripheral nerve
engineering.78 The group demonstrated that two biomaterials, collagen and polyurethane
could be printed to produce a scaffold with good biocompatibility and optimal mechanical
properties.78 The outer porous layer of polyurethane and internal orientated filaments of
collagen provide an ideal peripheral nerve conduit.78
Tissue Engineering
6. Discussion
Polyurethanes offer an exciting biomaterial for 3D‐printing fabrication due to their
modifiable chemical, mechanical properties and biodegradation properties. To date, most
groups are maximizing polyurethane’s ability to melt at high temperatures utilizing FFF
printers to create precise, customized scaffolds with suitable mechanical properties.
Encouragingly, 3D scaffolds with determined gradients, geometries have been formulated
and proven in vitro and in vivo applicability to generate new tissue using polyurethane
material. The mechanical properties of thermoplastic polyurethanes scaffolds can be
tailored to meet certain tissue requirements such as cartilage. Several studies, report the
3D‐printing orientations and infill density of FFF printing needs to be optimized to provide
the required cellular responses, which is frequently carried out with other polymeric
materials including PVA, PCL and PLA. Future work, will need to optimize the precise
geometrical scaffolds for different tissue types with polyurethanes to drive clinical
translation.
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Studies have shown the ability of FFF to print nanocomposite polyurethanes, creating
blends that can have specific mechanical and chemical properties to meet the regenerative
demands of the clinical problem. With the development of desktop extruders (FIlabot, Inc
USA), there is great potential to create different blends, which closely meet the
requirements of different clinical applications. Although in the studies identified, no
authors reported on the difficulties with extruding polyurethane filaments it is clear that
many parameters need to be optimized before achieving successful fabrication of tissue
engineered constructs. To ensure the filament is printable with standard FFF printer, a
consistent filament diameter and roundness need to be achieved, elimination of moisture
from the filament and avoidance of the creation of brittle filaments that are easily
destroyed by the FFF feeder mechanisms. Future work utilizing polyurethane filaments
should provide more detailed extruder parameters to widen the uptake of polyurethane
FFF printing.
One potential draw back for the tissue‐engineering field is that the high temperatures
Tissue Engineering
mean FFF printing it is not suitable for cell printing alongside scaffolds manufacture.
Similarly, few studies have utilised low temperature deposition to fabricate 3D‐
polyurethane scaffolds with patterned geometries. However, the freezing process is also
not applicable for material and cell simultaneous printing. Bioplotting fabrication has
shown a potential solution to this manufacturing hurdle.
Bio‐printing is another additive manufacturing technique, which aims to create functional
biomimetic composite tissues, which match native tissue, usually incorporating cells and
scaffolds materials. Bioplotting of polyurethane to create specific porous structures has
shown to be successful. However, more interestingly, water based polyurethane
dispersions have shown to be printed at low temperatures and allow for cell printing. By
printing waterborne polyurethane as nanoparticle dispersions and with viscosity
enhancers such as PEO61, cell‐material scaffolds have been fabricated. In addition,
waterborne polyurethanes allow for the incorporation of growth factors, to allow for the
polyurethane to closely mimic the native extracellular matrix environment. Such
polyurethanes offer great scope in the future to create functional bioinks for tissue
engineering applications.
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SLA polyurethane printing is in its infancy with very few studies demonstrating its efficacy
or limitations. This technique requires toxic photo‐initiators that have the potential to
remain in the final product, causing long‐term biocompatibility obstacles. The uptake of
the fabrication technique will need further exploration into the chemical modification of
the polyurethane structure to incorporate photo‐initiators. Furthermore, sinter laser
sintering has not been currently investigated for polyurethane 3D‐printing, which may
offer a different approach.
In summary, current evidence demonstrates that FFF printing of polyurethanes for
biomedical applications currently seems the most promising for clinical translation to the
clinical setting due to the flexibility in controlling the mechanical properties of
polyurethanes, ease of use and low cost. However, bioplotting is likely to have a significant
impact on the field of regenerative medicine due to the ability to print cells with the
polyurethane scaffolds.
Tissue Engineering
7. Conclusion
Overall, 3D‐printing using polyurethane is still in its infancy, but holds great opportunities
to create precise anatomical cell laden scaffolds for medical applications. The
polyurethane family is being predominantly being explored via FFF printing for biomedical
applications, demonstrating the creation of scaffolds for tissue specific applications with
tailored shape and geometry in high resolution. Water‐borne polyurethanes have shown
great potential in bioplotting with the capability of printing cells and scaffolds together,
creating patient specific tissues and organs. The clinical translation of utilizing
polyurethane for organ fabrication looks promising due to versatility of the polymer’s
physical and chemical traits.
8. Acknowledgements
The Winston Churchill Fellowship provided MG a research fellowship to visit the laboratory
of DWH.
9. Disclosure Statement
No competing financial interests exist.

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Name of the Reprint Author:
Dr Michelle Griffin: 12michellegriffin@gmail.com
Division of Surgery & Interventional Science, University College London, London,
United Kingdom, NW32AW, 02077940500.

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Figures and Tables Headings
Table 1. Advantages and Disadvantages of different additive manufacturing techniques.
Taken and adapted from [44‐46].
Different 3D printing Techniques
Technique Process Advantages Disadvantages
Fused filament Extrudes filaments. Good mechanical properties; Need filament form of material.

fabrication solvent not required; low Material processed at high
cost; multi material capability temperatures not suitable for cell
printing.
Low temperature Low temperature chamber prints Low temperature; can Freeze‐drying required

deposition material. incorporate biomolecules Need low temperature
chamber/platform for the process.
Stereolithography Laser scanning and UV induced Smoother surface; high High cost; possibly high temperature;

curing. resolution; fast processing toxic
uncured resin
Selective laser Laser scanning and heat induced No supports needed during Rough surface finish; high temperature

sintering sintering. manufacturing; high
resolution; fast processing
Tissue Engineering
Bioplotting Syringe Pressurized syringe extrusion, and Cells and hydrogels can be Low mechanical strength; slow

driven
process heat or UV assisted curing. printed processing; low
Pneumatic Piston
accuracy
Table 1

Tissue Engineering

and adapted from [47].

Table 2. Flexible polyurethane filaments commercially available for 3D printing. Taken
30
Page 30 of 34
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Page 31 of 34
from [Adapted from 27].

polyurethanes using a one‐stage process and a two‐stage process. Taken with permission
repeating structure Taken with permission from [25]. [B] Typical synthesis of
Figure 1. [A] Chemistry of Polyurethanes [A]. Schematic of polyurethane linear moiety
31
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Tissue Engineering
Figure 2. Stimulated Body fluid nucleation of Three‐dimensional Printed elastomeric
scaffolds for enhanced osteogenesis. A] Computer aided design (CAD) stimulations and B‐
C] photographs of 3D printed and 3D printed polyurethane nucleated scaffolds. D]
Fluorescence microscopy analysis of 24‐hour hFOB cell growth on nucleated 3D printed
TPU scaffolds. Excellent cell attachment and spreading was observed on all samples
including non‐nucleated control. Scale bar 100 m. E] Scanning electron microscopy (SEM)
of nucleated polyurethane scaffolds with corresponding quantified Ca2+ as a function of
nucleation time in SBF. F] Total nucleated calcium on TPU scaffolds after various SBF
incubation periods. Data are mean ± standard error of the mean, n = 5, *p < 0.05. Scale
bar = 100 μm.Taken with permission from [48].

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Figure 3. Examples of Fused Filament Fabrication (FFF) Polyurethane Printing.
Nanocomposite FFF printing. A) Polyurethane/polylactice acid (PLA)/graphene oxide (G0)
nanocomposites filament printing. B) Photos of FDM printed TPU/PLA/GO
Tissue Engineering
nanocomposites. (b) 3D printed cuboid specimen and dumbbell specimen for mechanical
testing. (c) 3D printed Ultimaker robot. (d) 3D printed words. (e) 3D printed microlattice.
(f) 3D printed microlattice under bending. Taken and with permission from [50]. Indirect
three‐dimensional printing: A method for fabricating polyurethane‐urea‐urethane based
cardiac scaffolds. A] Scanning electron microscopy images of the PVA porogens in the
three different sizes (above) and the PUUU scaffolds (below) that they generated. The
displayed images were taken of the XY plane of the porogens/scaffolds (parallel to the
fiber/channel direction). The stacks of 300 and 400 μm thick porogens created aligned
channels in the PUU scaffolds. The 500 μm thick porogens deformed under their own
weight, resulting in a distorted scaffold architecture. The scale bar represents 500 μm. B]
Confocal microscopy images of cardiac α-actin (a marker of cardiac myocytes) and DAPI
(cell nucleus) stained sections of cell suspension and cell aggregate seeded PUU scaffolds
after 3 and 7 days in culture. The scale bar represents 25 μm. Taken and with permission
from [53]. 3D‐printing with polyurethane triblock co‐polymers. A) Example of the physical
image of the TPU multi‐block copolymer manufactured by fused deposition modelling in
the A) dry and B) hydrated state. C‐D). Scanning electron microscopy images of the TPU
images in the dry state. Taken and adapted from [54].
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Tissue Engineering
Figure 4: Photosensitive polyurethane 3D printing. A) The schematics of the
manufacturing process of the water‐based polyurethane based photosensitive materials;
The Raman spectra of the B) water‐based light‐cured polyurethanes and C) water‐based
thermoplastic polyurethanes with or without water removal processes; D) The images of
the printed scaffolds; E) The images of the designed (left) and printed (right) porous lattice
structures. Taken and adapted from [69].

2019 The Current Versatility of Polyurethane 3D Printing For Biomedical Applications

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2019 The Current Versatility of Polyurethane 3D Printing For Biomedical Applications

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Tissue Engineering

Interventional Science, University College London, London, United Kingdom,

polyurethane‐based materials for biomedical applications. A summary of the chemical

Polyurethane, 3D‐printing, additive manufacturing, synthetic polymer, fused deposition

their good biocompatibility versatile properties. With advancements in 3D‐printing

Polyurethane scaffolds can be fabricated using multiple techniques including

based.24‐27 Polycarbonate‐based polyurethanes are more durable, with good mechanical

determines its mechanical properties, thermal stability and hydrolytic resistance.24‐27 The

printing, the nanocomposites demonstrated good biocompatibility with NIH3T3 cells,

green chemistry‐derived isocyante free aliphatic polyurethanes they could create

process for the production of bilayered small‐diameter nanofibrous tubular

Three‐Dimensional Printed Elastomeric Scaffolds for Enhanced Osteogenesis.

57. Merceron, T.K., Burt, M., Seol, Y.J., Kang, H.W., Lee, S.J., Yoo, J.J et al.

Technique Process Advantages Disadvantages

Fused filament Extrudes filaments. Good mechanical properties; Need filament form of material.

Low temperature Low temperature chamber prints Low temperature; can Freeze‐drying required

Stereolithography Laser scanning and UV induced Smoother surface; high High cost; possibly high temperature;

Selective laser Laser scanning and heat induced No supports needed during Rough surface finish; high temperature

Bioplotting Syringe Pressurized syringe extrusion, and Cells and hydrogels can be Low mechanical strength; slow

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