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76 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside
treatment, such as electrochemical deposition, chemical modification, and alkali-heat treat-
ment, is usually carried out to enhance the bioactivity of porous metal implants. As part of
the metal 3D-printing process chain, heat treatment can be used to tailor biocompatibility
and mechanical properties simultaneously [46].
In addition to extensive research on the 3D printing of polymers and metals, 3D printing
of ceramics is now actively under development. The ability to fabricate ceramic compo-
nents of arbitrarily complex shapes has been extremely challenging without 3D printing. In
many cases, the 3D-printing step utilises a ceramic slurry or blend of material to build a
part that can be sintered like the process for bound metal deposition. Promising explora-
tions have been made in the biomedical field, including the fabrication of components for
tissue engineering, which generally require less precision in resolution and surface finish,
as well as porous features of the printed parts for cultivation purposes. Biocompatible
ceramics such as HA, calcium phosphates (CP), and TCP are often used in 3D printing of
scaffolds for bone replacement. A pre-ceramic polymer, i.e., silicon resin as a binder, which
also reacted with fillers to form desired ceramic phases, was 3D printed to CaSiO
3
-based
biocompatible ceramic parts with a porosity of approximately 64% by volume [47].
Ceramic SLS has also become increasingly popular in biomedical applications, particu-
larly in the fabrication of customised complex and highly cellular biocompatible scaffolds
for tissue engineering. These fabrications generally involve high volume fractions of binder
phases of up to 60 vol%, and so geometrical accuracy and surface roughness are not strictly
required for these applications, although macro-porous structures are often customised in a
controllable manner [48]. Examples include bone implants made by ceramic–polymer
blends, such as HA-TCP [49], PCL-HA [50], and PEEK-HA [51]. Ceramic–glass compos-
ites have also been investigated for the fabrication of biocompatible scaffolds, such as
HA–phosphate glass [52]. In these applications, the low-melting point polymers and
glasses serve as liquid-phase binders during SLS to facilitate densification. For 3D printing
of ceramics using FFF, composite filaments are prepared by densely loading ceramic par-
ticles into thermoplastic binders [53]. After printing, the printed ceramic part is subjected
to binder removal and sintering to achieve densification.
Photo-polymerisation methods have shown greater potential over powder bed fusion in
the manufacture of 3D ceramics parts [54]. Slurry-based photo-polymerisation methods
such as SLA, DLP, and two-photon polymerisation for ceramics fabrication have shown
promise. A controllable feature resolution and surface finish with desirable mechanical per-
formance can be achieved for the fabricated parts. A variety of commercial machines are
now available for the fabrication of complex 3D ceramic components. DLP is more favour-
able for widespread use due to lower price [55]. Aerospace and medical industries are the
two most promising markets for ceramic 3D printing. However, high standards and com-
pliance challenges result in complex and long regulatory pathways for commercialisation.
4.4 3D-Printed Personalised Medical Devices
Medical implants fabricated by 3D printing have demonstrated unique features and/or
functions that were not possible or too costly to fabricate by traditional manufacturing
techniques such as injection moulding. It is imperative to understand the core mechanisms
relating to the materials in 3D printing; for example, the key characteristics of materials
suitable for 3D printing include thermal stability, flowability, printing temperature, and
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3D Printing for Medical Device Applications 77
reproducibility, etc. Additional material features such as biocompatibility, biosorption,
self-healing, shape memory, self-assembly, self-deployment, etc., can add extra advantages
in the design and manufacturing of medical implants [56]. Probably the greatest advantage
of 3D printing is related to the rapid fabrication of patient-specific or personalised designs
of medical implants. Surgical treatments involving 3D-printed medical implants have suc-
cessfully demonstrated their profound benefits. In this section, selected medical implants
enabled by 3D printing are reviewed.
4.4.1 Vascular Repair Devices
Coronary and other vascular diseases have been the leading causes of morbidity and mor-
tality worldwide. Autografts, xenografts, and bioengineered extracellular matrix have been
explored as treatments. 3D printing offers design freedom for stents that has not been
possible before. SMPs have shown promise as polymeric stents owing to their self-deploy-
ment capabilities without auxiliary devices, reducing catheter size for delivery and vascular
biocompatibility. Resorbable SMPs could prevent the negative effects of strain induced
hardening in conventional polymers impacting resorption uniformity. Rather than using a
product with predetermined size, 3D-printed personalised stents with desirable final diam-
eter were crimped onto a much smaller diameter balloon or into a smaller sized catheter
sheath to enable it for easy implantation and correct placement. With time as an addi-
tional dimension in the 3D printing, 4D printing better reflects this unique advantage. After
being implanted and placed at the right site in the anatomy, the stent then recovers to its
original diameter triggered by body heat without the need of balloon expansion and limit
stent migration [57, 58]. High-resolution projection micro-stereolithography (PµSLA)
has been demonstrated to be efficient in fabricating stents utilising SMPs [59]. Direct-
write printing of photo-curable PLA-based inks is another viable fabrication technique for
4D printing stents with magneto-responsive materials, allowing them to be magnetically
remotely guided to the placement destination [60]. A highly stretchable elastomer with a
semi-interpenetrating polymer network (IPN) structure was 4D printed through UV light
assisted direct-ink-writing. This semi-IPN elastomer features a urethane diacrylate for UV
crosslinking and a crystalline PCL component in the network. The self-healing capability
of this material can repair vascular tissue in 3–5 minutes [61]. The world’s smallest stent,
just 50 µm wide and 0.5 mm long, 40 times smaller than any other stents produced, was
only achievable by means of 4D printing. This type of small stent could help widen life-
threatening constrictions of the urinary tract in foetuses in the womb. The shape memory
properties give the stent the fourth dimension that once the stent is deformed, it remembers
and returns to the original expanded shape when facing body temperature over time [62].
Resorbable and personalised occluders enabling remote control were 4D printed through
PLA. Introducing microgrooves to polymeric stent surfaces to form micropatterns has pro-
moted endothelial cell attachment and alignment along stent grooves, due to the improved
surface hydrophobicity. It is suggested that SMPs with improved surface and material char-
acteristic could be possible for next-generation blood-contacting devices [63].
4.4.2 Splints
For medical implants, a critical aspect is the geometry that becomes even more critical and
challenging for paediatric patients to allow the implants’ proper function. Traditionally,
prefabricated medical implants have difficulties in accommodating for the growth over
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78 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside
time in paediatric patients. This even becomes more critical and challenging for infants; for
example, with tracheobronchomalacia (TBM). TBM is a life-threating condition where the
airway of the patient excessively collapses during respiration. Under provisions for emer-
gency clearance from the FDA, a 3-month-old infant with TBM became the first baby to
receive treatment by a 3D-printed resorbable tracheal splint created by Professor Hollister
and Dr Glenn at the University of Michigan [64]. In another case, an infant with localised
TBM was treated with a 3D-printed resorbable airway splint that resulted in improved
ventilation [65]. Patient-specific resorbable airway splints based on PCL, with 4% of
hydroxyapatite 3D printed by SLS, demonstrated initial clinical efficacy in treatment of
critically ill children with severe TBM. No child required removal or replacement of the
splints. The first four children to receive splints are all alive with sustained significant clini-
cal benefit for more than two years after splint implantation [66]. 4D printed implants
could provide an answer for the accommodation of shape change fitting to growth. In a
clinical study, personalised 4D printed external airway splints were successfully implanted
in infant patients. A splint based on biocompatible and resorbable polymer blend was
designed to accommodate the growth of the airway, consequently preventing unwanted
compression [67]. Until further data is presented, PCL appears to be the most suitable
material for splint manufacture and the corresponding applications [68].
4.4.3 Nerve Guidance Conduits
Nerve guided conduits (NGCs), as alternatives to nerve autografts and allografts, are tubu-
lar devices that facilitate nerve regeneration by meeting physical, chemical, and biological
requirements. The emerging 3D-printing technology has led to remarkable advances in
fabrication and functionalisation of personalised NGCs in peripheral nerve repair and
regeneration. A recent overview [69] summarised materials that have been used in 3D
printing of NGCs including PLA, PCL, PLGA, collagen, and photo-curable monomers like
gelatin-methacrylate, silk-methacrylate, alginate-methacrylate, etc. These materials exhib-
ited both advantages and disadvantages for their application in NGCs. 3D-printed NGS
based on PLA, PLA/PCL, and PLGA from inkjet printing displayed low mechanical
strength. High resolution SLA printing has been shown as a better alternative to fabricate
NGCs of different complexity and size using photocuring biomaterials.
SMPs represent the possibility to produce minimally invasive medical devices including
NGCs. Soybean oil epoxidised acrylate was used as an ink for SLA 4D printing for an
NGC with several desirable functions for nerve tissue regeneration [70]. The cured reactive
polymer by UV light allowed for easy readjustments of the NGC through thermal stimula-
tion during implantation. The axial tension force generated from this stimuli-responsive
polymer can guide tissue regrowth. However, possible cytotoxicity of residual photo-initi-
ator and uncured resin may limit their clinical applications. There is a great need for safe
bio-inks for 3D printing.
4.4.4 Tissue Engineering
Tissue engineering bridges material engineering and life science to create scaffolds or
organs to regenerate, restore, replace, improve, and maintain tissues damaged by injury,
disease, or congenital disability [71]. An ideal scaffold must provide a surface to allow cell
attachment and a continuous 3D inter-connected porous structure to promote extracellular
matrix formation and vascularisation. 3D printing allows fabrication of scaffolds with more
controlled and precise structures than any other techniques so far [72].
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3D Printing for Medical Device Applications 79
Bone regeneration has been one of the focus areas of tissue engineering. Several works have
demonstrated that inclusion of osteoconductive fillers to polymers or composites can promote
osteosis inclusion. Porous scaffolds with biomimetic architecture are highly promising for
bone tissue engineering applications. Bioresorbable porous composite scaffolds constituting
PLA and HA were 3D printed by FFF. Ceramic particles inhibited the growth of cracks during
compression-heating-compression cycles, whilst porous PLA/HA scaffolds recovered their
initial shape. In the subsequent reheating process, the self-healing effect of the scaffold nar-
rowed the cracks. With 15% HA, the 3D-printed porous scaffold was able to recover 98%
of its original shape, which merited it as a candidate for self-fitting implants for small bone
defect replacement [73]. Incorporation of methacrylates bearing 2-ureido-4[1H]-pyrimidinone
units to PCL dimethacrylate macro-monomers provided 4D printed structures with self-heal-
ing properties. Even after the healing process, the printed objects still exhibited remarkable
shape memory properties [74]. Similar results were observed in FFF 3D-printed micropo-
rous osteoconductive bone grafts based on amphiphilic resorbable PLGA-b-PEG-b-PLGA
copolymer with 25% of HA. The SME and PEG hydration-induced stiffening and swelling
enabled a facile surgical delivery and stable fixation in critical long bone defects in rats [75].
Magnetically induced SMPs enable remote non-contact control and selective actuation. 4D
printing of these materials to biomimetic scaffolds with pre-determined appropriate morphol-
ogy and microstructure provide better compatibility to the geometry and better supporting
functions. PLA with 20% of ferromagnetic nanoparticles (Fe
3
O
4
) was 3D printed into porous
scaffolds through FFF. The scaffolds not only had excellent shape memory properties but
also processed adequate mechanical strength to resist external load generated during motion.
Water borne resorbable polyurethane containing iron oxide nanoparticles as 3D-printing ink
was developed as customised bone substitutes for bone tissue engineering applications. The
ink containing 500 ppm of iron oxide nanoparticles was designed to not only promote osteo-
genic induction but also to improve shape fixity capability. The scaffolds were printed by
low-temperature FFF and exhibited high shape recovery at 37 °C. The iron oxide nanoparticles
could be released gradually from the scaffolds and further improved the osteogenesis [76]. A
3D-printed PCL mesh serving as inner core, for patient-specific ear-shaped cartilage, was used
clinically for the first time for auricle reconstruction in five patients and achieved satisfactory
aesthetical outcome with mature cartilage formation for 2.5 years [77].
Natural polymers have been successfully employed in 3D printing of tissue engineering
scaffolds. In 1999, the first 3D bio-printed bladder using the patient’s own cells and a col-
lagen-PGA composite as the scaffold was implanted into a human [78]. Poieskin
®
, a prod-
uct from Poietis, became the first commercially available bio-printed human tissue based
on laser-assisted 4D bioprinting in 2018. This product consists of a dermal compartment
composed of primary human fibroblasts embedded in a collagen I matrix [79]. BellaSeno
has developed a 3D-printed porous resorbable breast scaffold based on Evonik’s RESOMER
polymers to avoid the use of silicone implants and respective side effects [80]. In 2019,
Organovo announced a successful automated production of kidney organoids with detailed
kidney tissues through its advanced bioprinting technique, which revealed the world’s first
commercial 3D bioprinter to print human tissues [81].
4.4.5 3D Printing in Dentistry
Dental implants were the pioneer in adapting 3D-printing technologies in the medical field in
the 1990s. Advances in 3D printing and imaging technologies have fostered applications in
clinical and experimental dentistry. Even now, nearly all structures that dental professionals
produce for patients can be made by 3D printing [82], such as in oral surgery, prosthodontics,
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80 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside
periodontics, endodontics, and temporomandibular joints (TMJ). 3D printing has resolved
many long-standing challenges in dentistry, for example, replacing damaged TMJ discs. An
artificial TMJ disc was fabricated using polyvinyl alcohol (PVA) hydrogel crosslinked by cyclic
freeze-thaw and reinforced by 3D-printed PCL, which induced disc defect repair for 12 weeks.
Such a disc demonstrated comparable mechanical strength to a natural disc and providing addi-
tional advantages regarding better fatigue resistance, hydrophilicity, less creep, and improved
cell adhesion [83]. The first human case of treatment of a large periodontal osseous defect with
a patient-specific scaffold, based on 3D-printed PCL powder by SLS with signalling growth
factor was reported in 2015. The scaffold remained covered for 12 months, exhibiting a 3 mm
gain of clinical attachment and partial root coverage [84]. Separately, 3D-printed PLA/HA scaf-
folds loaded with dental pulp stem cells were explored in an animal study for the feasibility of
tooth regeneration. HA promotes a high degree of mineralisation; however, after nine months
of initial surgery, the scaffolds were not completely absorbed [85]. These studies revealed that a
more rapidly resorbing matrix with a healing timeframe shorter than 1 year together with a less
bulky design would be more suitable for oral tissue regeneration around teeth. Fast bioresorb-
able polymers, for instance PDO with a degradation time around 6 months, might be a good fit
for these applications, for example, by FFF of PDO filament.
Non-bioresorbable polymers, such as PEEK and acrylics, are two prominent polymers
extensively used in dentistry. As alternatives to metallic and ceramic materials in clinical
practice, PEEK dental implants ranging from surgical guides, aligners, fixed and remova-
ble denture, bridges, and others seem to provide patient comfort and satisfaction due to the
lightweight, durability, wear resistance, and biocompatibility [26, 86]. Evonik has manu-
factured medical-grade PEEK for extensive dental applications. FFF is still the leading
technology in 3D printing of PEEK. Lack of printing precision currently limits its wide
dental application by 3D printing. With the fast advances in new additive manufacturing
technology, personalised PEEK dental devices by 3D printing are expected to provide
more convenience to dentists and comfort to patients. Acrylic polymers have been well
adapted in 3D-printing dentistry, not only in clinics and dental labs, but are also commer-
cially available for mass production. Invisalign
®
custom-made clear aligners are examples
of 3D-printed commercial products by SLA, with Align Technology’s proprietary technol-
ogy including acrylic materials [87] to straighten teeth. ClearX, a clear SMP sheet devel-
oped by K Line Europe, has been 3D printed into 4D aligners with shape-shifting property
within the oral temperature range that can be easily modified and reused [88].
3D-printing technology can help create novel dental implants with rough or porous sur-
face finishing. However, seeming to be attractive in many medical applications, these rough
or porous surfaces in dentistry may generate challenges many years later [89]; for example,
discoloration and promotion of bacterial or fungal growth, leading to odours. Yet, 3D print-
ing has not been widely used in fabrication of crowns or restorations due to a lack of material
providing sufficient mechanical properties, accuracy, and fit to tooth preparations. Material
innovation is key to further adapting 3D printing in dentistry. The ability to produce complex
geometries and accurate dimensions, which cannot be produced by other techniques such as
milling/machining, remains the unique advantage of 3D-printing technology in dentistry.
4.4.6 3D-Printed Orthopaedic Devices
Customised implants enabled by 3D printing are arguably the most ground-breaking
aspect for orthopaedic surgery, for example, in joint replacements and bone recon-
struction therapies. Without compromising the mechanical properties, PLA-based
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3D Printing for Medical Device Applications 81
osteoconductive composites are an important and challenging problem for orthopaedic
applications when the implants are used in load bearing applications. The inclusion of
rigid fillers such as HA can increase the melt viscosity of the composites. Designing
and printing the scaffolds with this composite composition would need to be taken
into consideration to obtain scaffolds with desirable properties. Reliable fixation of
a scaffold at the implantation site without additional binders which can be achieved
by 3D printing of the composites, is extremely beneficial. 3D-printed scaffolds can
be easily moulded to patient-specific bone defect sites; for example, as guided bone
regeneration (GBR). In a rabbit calvaria model, 3D-printed PLA GBR demonstrated
biocompatibility and integration with bone defect margin to enhance bone augmenta-
tion [90]. Photothermal-responsive shape memory bone scaffold was 3D printed from
β-TCP/poly(lactic acid-co-trimethylene carbonate) and black phosphorous nanosheets
and exposed to near-infrared radiation prior to implantation, enabling shape remoulding
and precise fitting in irregular bone defects. Once implanted in the desired place, the
temperature dropped to body temperature and the scaffold displayed mechanical prop-
erties similar to those of cancellous bone. This method successfully treated bone defects
of irregular shapes [91].
There are a few end-use orthopaedic implants being 3D printed. Orthofix Medical
has launched a series of 3D-printed spacer systems designed for use such as in Posterior
Lumbar Interbody Fusion surgeries [92]. Onkos Surgical received 510 (k) clearance from
the FDA for the modular 3D-printed BioGrip collars with nano HA treated surfaces [93].
4Web Medical utilises engineering principles to produce 3D-printed spin implants that
may actively participate in the healing process [94]. Cleared by the FDA for commercial
sales in the US, Smith & Nephew now offers 3D-printed knee implants featuring porous
surfaces that can bind more naturally to the bone without the need of cement [95]. In 2020,
the first 3D-printed PCL-based scaffold, TruMatch Graft Cage in a highly customisable
manner from Depuy Synthes, was implanted into a patient to restore long bone injuries for
the first time [96].
4.5 Regulatory
Regulatory agencies play a significant role in the medical device manufacturing process.
These bodies are governmental organisations with legal authority to select devices that can
be sold on the market through a scientific support and risk analysis process. At a fundamen-
tal level, they assign accountability of risk to the maker of a device through the legal
system.
In the US, prior to 1906, there was minimal oversight into the manufacturing and distri-
bution of food and drug products. In 1938, the Federal Food, Drug, and Cosmetic Act
(FD&C) was passed and ultimately led to the modern FDA. This legislation extended pre-
vious regulation to overseeing of medical products, drugs, cosmetics, and therapeutic med-
ical devices. It also granted authority for inspections at facilities manufacturing these
products. Device regulation further evolved in 1976, with the designation of device classes
and the pathways for Premarket Approval (PMA) and premarket notifications (510 k).
Additional amendments from this period introduced pathways for investigational devices
through the Investigational Device Exemption (IDE) process. New post market require-
ments also included registration of manufacturing establishments, tracking of device
.
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82 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside
adverse events, and gave the FDA power to ban devices deemed unsafe or not effective.
After 1990, regulation was extended to improve post market device surveillance, allow
device recalls, and provided flexibility for ‘Humanitarian Device Exemption (HDE)’
devices targeted towards rare diseases [97].
Due to the rate and scale of the modern global market, regulatory bodies worldwide have
evolved throughout history to serve their region’s interests. The FDA has been the most
centralised organisation historically, with activities in countries that manufacture products
marketed only in the US. The modern European Medicines Agency (EMA), headquartered
in Amsterdam, has acted to harmonise regulatory activities across Europe [98]. Regulatory
bodies also exist in other countries including Japan, China, the United Kingdom, Canada,
India, Russia, Singapore, Australia, Brazil, and Switzerland [99]. Many international stand-
ard think tanks have aided manufacturers and regulatory bodies in developing harmonised
language, test methods, and processes to improve efficiency; however, each organisation
acts independently, and devices are not typically approved automatically across markets.
The designation of a medical device by a regulatory agency is highly dependent on its
intended use and the risk associated with treatment. This requirement has not been altered
with the proliferation of 3D-printing technology. Any printed device intended to treat a
condition, regardless of manufacturing means, would still be subject to the parameters
outlined under guidance. It follows that anyone designing or printing a device would then
be responsible for its lifecycle once used [100].
As 3D-printing manufacturing extends to more devices, regulatory definitions need to be
refined and clearly outlined. Risk-based strategies are often employed to identify a device’s
classification; however, quantitatively defining terms like ‘low risk’ or ‘healthcare facility’
become more complex when devices can be printed easily [101]. Consider an anatomical
model that is 3D printed in a hospital’s surgery suite. If the model were used as a surgery
guide for a specific patient there would likely be higher risk involved than if the model were
used in a general training scenario. The regulatory impact of each case might be highly
divergent. Due to the small and extensible footprint of many 3D-printing technologies, the
lines can become blurred between a medical service provider and a medical device manu-
facturer. Whilst producing patient matched parts is highly convenient and efficient, manu-
facturing these devices at the point-of-care could potentially cause the provider to fall under
the designation of a medical device manufacturer. This adds an increased level of complex-
ity, additional overseeing, and expense to the provider [102]. Rarely are small-scale medi-
cal providers staffed to maintain the quality system framework sufficient for regulatory
body overseeing. Any design manufacturing parameters must be controlled so that all parts
fall within the scope of the device classification and any validated specifications. This
requirement extends to any computers, software, or hardware involved in the manufacturing
chain. Furthermore, for each device that is produced, the burden of proof remains with the
manufacturer to assure that it is cleared through the appropriate classification system [103].
Prior to 2012, there were limited 3D-printed devices cleared for use outside of the dental
market. A highly visible case in 2013, involving a lifesaving, 3D-printed tracheal stent/
splint, was cleared for emergency use by the FDA [65]. Shortly after, building interest and
maturation of the technology led to the formation of the ‘Additive Manufacturing Working
Group.’ This group further improved guidance related to AM from the FDA through inter-
active discussions and technical guidance [104]. In 2021, the FDA issued a further public
request for a response from the industry. Close collaboration with industry members and
regulatory bodies should further broaden the range of 3D-printed devices that are cleared
on the market in the future.
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3D Printing for Medical Device Applications 83
The agility and extensibility unique to 3D printing played an unprecedented part during the
COVID-19 pandemic. In the early stages of the pandemic, the availability of personal protec-
tive equipment and lifesaving equipment, such as ventilators, became scarce. To minimise
loss of life, the FDA granted Emergency Use Authorization (EUA) for an array of medical
devices. This cleared the use of existing devices to be used across their designation with
modification. For example, certain devices such as anaesthesia gas machines and positive
pressure breathing devices could be modified or used as ventilators in emergency settings.
More than 50EUA medical device clearances were granted during this period and included
parts such as the Formlabs BiPAP adapter used to convert sleep apnea machines into ventila-
tors [105, 106]. Additionally, a network of Non-Traditional Producers (NTPs) consisting of
hospitals, hobbyists, 3D-printing manufacturers, governmental agencies, and universities
used 3D printers to produce over 50 million parts in a 5-month period. These parts included
face shield components, nasal swabs, ear savers and mask parts, and ventilator components.
Parts were designed by experts and then submitted to the National Institute of Health’s 3D
Print Exchange. The reviewed models were given a ‘Clinically Reviewed’ status [107].
4.6 Future Perspectives
Rapid progress of nearly every aspect of 3D-printing technology in recent years has led
to more sophisticated, patient or site-specific medical implants. This trend will continu-
ously evolve in the direction of making 3D or 4D printing an easily adaptable technique
and tool in personalised medical devices. Solutions might be found, or progress made, to
resolve current limitations or challenges. Ideally, 3D-printed medical devices having sound
mechanical properties and surface characteristics to mimic surrounding tissue and encour-
age cell attachment and proliferation are beneficial to biomimetic implants. To achieve this,
not only would such a polymer or material be available, but also a 3D-printing technique
would be well tailored amongst the materials, printers, and processes. In certain applica-
tions; for example, FFF printed devices’ function and structure sometimes are constrained
by the current printing resolution threshold. More fine detailed structure can be achieved
by; for example, SLA, DLP, or PµSLA. Yet, the prevailing materials in the SLA process
bearing photo-reactive moiety, selection of such a resin for medical implants requires care-
ful consideration of its biocompatibility and regulatory compliance.
Bioresorbable polymers eliminate the need for subsequent secondary surgery to remove
medical implants, which reduce medical care costs and improve patients’ comfort.
Nonetheless, safe elimination of the degradation by-products from the body and a predict-
able degradation time window are still the key fundamental requirements in development
of new bioresorbable polymers to fit various biomedical needs via 3D printing.
Smart materials, such as stimuli responsive polymers, and rapid advancement in 3D
printing enabled the possibility of a more fascinating 4D printing technology which would
lead to more innovative solution and advanced technology towards more personalised treat-
ment. 4D printing remains in its early stage and behind more prevailing 3D-printing tech-
niques due to the limited availability of suitable printable resins. Combination of multiple
and appropriate stimuli responsive materials can provide a wonderful opportunity in medi-
cal implants design, fabrication, and applications creativity. For example, smart medical
devices with different functions (e.g., functions in gradient) and degradation rates to match
complex tissue regeneration and functions requirement expect to be enabled by 3D/4D
printing individually or through a printing process combination. Current materials, smart
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84 3D Printing of Pharmaceutical and Drug Delivery Devices: Progress from Bench to Bedside
materials, and 3D/4D-printed structures are still mainly investigated at the macroscale,
represented by such as mechanical properties and surface finish. Towards an understanding
of materials for 3D/4D printing at the microscale, for instance, interaction with localised
microenvironment or response to multiple physiological signals would lead to more pre-
cisely controlled, multifunctional, point-of-care, and biomimetic medical implants.
Last but not least, similar to other new technologies, high cost and lack of sufficient data
to comply with regulatory requirements remain challenges for 3D printing which are vital
to individualised medical implants. Satisfaction of patient-specific treatment and increased
patient compliance propels the further advance of 3D-printing technology.
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