Medical implants are crucial to modern-day medicine and are used to treat a lot of medical conditions. Additive manufacturing has become one of the most advanced and versatile ways for producing different metal implants, from acetabular cups to stents. Additive manufacturing is highly beneficial for medical implant success because not only can the geometry of the implant be designed and customised to fit the exact space needed, but the surface properties of the implant can also be tailored to improve biocompatibility and osseointegration – which helps the implant stay longer in the body without rejection.
In recent years, additive manufacturing has expanded into other modalities that can print biological materials. This is bioprinting and involves the growth of cells to create new tissue and for developing more biocompatible implants. Until recently, a lot of bioprinting has been ex vivo and involved printing implants and structures outside of the body and then performing a procedure to introduce them to the patient. Recent years have seen the development of experimental in vivo and direct-to-body bioprinting techniques, where biological tissues and implants could potentially be printed directly onto or into the body.
The growth of bioprinting
“In traditional additive manufacturing, the biggest application is to help anatomical matching. Based on patient CT/MRI data, 3D printing can fabricate implants that precisely match the patient’s anatomy, such as titanium alloy cranial repair plates,” says Professor Jianfeng Zang of the Huazhong University of Science and Technology, “whereas bioprinting enables the production of degradable scaffolds loaded with growth factors or drugs, such as PLA/ PCL scaffolds for cartilage repair.”
The need for tissue-engineered products in clinical settings has grown with a lack of organ donors and the increase in transplant rejection. This has meant there is an increased need for laboratory-generated implants that mimic human tissue. A lot of this was done in the past by seeding stem cells into scaffolds and implanting them in the body. However, this often failed to replicate human tissue. Now, continued advancements in additive manufacturing have led to the field of bioprinting. Bioprinting has been used to create a range of tissues and implants that could potentially be transplanted into the body, alongside biomimetic organ and disease models that help researchers study human physiology – which are helping clinicians to treat diseases more effectively. This is on top of conventional additive manufacturing being able to create metallic implants for a range of ailments.
More recently, in vivo bioprinting – currently at an experimental stage – has attracted attention for its potential to print tissue constructs and implants at the site of need, which may improve integration.
“Although in vivo bioprinting technology is based on conventional additive manufacturing, there are some differences,” says Zang. “We need to use small instruments with small lumens because the printing scenarios are very complex and deeper anatomical sites demand greater flexibility, and only biocompatible materials can be used to create the implant.”
Both types of bioprinting involve embedding cells in a bioink (e.g. hydrogels and biomaterial scaffolds). For transplant-based bioprinting, the cells are incubated until the tissue fully forms, ready for implanting, whereas in vivo bioprinting directly deposits the bioink using a very small and flexible printing nozzle. While using light is one way to cure in vivo bioinks, Zang states that: “One of the most impressive emerging bioprinting advancements is acoustic volumetric printing, which delivers a liquid ‘sonic ink’ through catheters into the body, where external ultrasound triggers in situ solidification.”
Compared with conventional cell seeding approaches, bioprinting provides a uniform distribution of cells that allows tissues to be reconstructed accurately. “Compared with other methods, bioprinting can reach any desired location within human tissues through catheter structures,” says Zang. “Printing drug or medical devices directly onto tissues in a minimally invasive manner can help to heal damaged tissue and reduce the need for implant surgeries, so long as there’s a seamless integration between the printed material and the biological matter inside the body.”
Bioprinting can produce a range of customised implants that fix complex tissue defects with a much more efficient integration inside the body. This includes repairing cartilage, connective tissue, nerve structures, microvasculature and muscle tissue using a range of smart tissue patches, as well as implants that can enhance bone repair by delivering growth factors.
The move to clinical trials
While it may not be well documented, bioprinting is moving through clinical trials – much like advanced implants are using more traditional additive manufacturing methods. There have been clinical trials undertaken so far, most of which have focused on bioprinted in vitro models, but there have also been some implant clinical trials that have taken place too.
For the bioprinting of in vitro models, the majority of clinical trials have targeted different cancers, including ovarian, haematological, colorectal and pancreatic cancers – which have been led by different hospitals. These trials have focused on bioprinting tumour tissues and organoids. The other in vitro model trials have focused on using tissue models as drug screening platforms for optimising the delivery of drug treatments. One of the other clinical trials undertaken includes an in vitro study on building skin substitute materials, and while this study was an in vitro study, the end goal of the skin is implantation.
On the implant side, there are currently multiple clinical trials ongoing that are targeting different ailments. One example is using implanted bioprinted blood vessels to treat peripheral limb arterial disease, with the aims of the clinical trial focusing on device success rate and graft patency rate. Another example is the bioprinting of personalised tracheal structure implants for treating thyroid cancer, with the aims of these clinical trials focusing on the airway lumen opening rate, degree of granuloma formation and degree of inflammation. Two implant clinical trials have also focused on external medical conditions rather than internal ailments. One clinical trial has focused on treating microtia (underdeveloped ear). This clinical trial revolved around bioprinting an auricle based on autologous chondrocytes that was customised to the dimensions of the patient’s ear. The main outcomes of the study were based on safety and efficacy. Another trial conducted by ROKIT Healthcare involved bioprinting wound dressings for diabetic foot ulcers. Adipose tissue (derived from adipose stem cells) was used to print custom-fitting wound patches. In this completed trial, all subjects showed complete wound healing after 12 weeks, whereas the control group only had a 50% complete healing rate.
Currently, there are more model-based clinical trials due to the extra safety, ethical and regulatory risks associated with implants. Even though there are some clinical trial examples that have both been completed and ongoing, the volume is still quite low. However, this shows that bioprinting is now starting to make the transition from the bench to clinical stages, with the hopes that they will soon be at the patient’s bedside. This could still be a while off yet according to Zang, who noted that “to date, there is no single bioprinted FDA-approved product for clinical use that is commercially available in the market”.
However, even though bioprinted implants are making their way through clinical trials, there isn’t much transparency surrounding them, and many early-stage trials are potentially not being registered – so it could be that there are more out there than has been officially confirmed. More transparency and participation in registering clinical trials could eventually help clinicians compare bioprinting methods across trials and draw connections to clinical outcomes, which would eventually speed up the time to market for future bioprinted products – as the best approaches for different implants would be known to more people. But that is something that is for the future, and the challenges with regulations for bioprinting (and medical additive manufacturing in general) also need to be sorted before we see more clinical bioprinted implants.
FDA regulations are ambiguous
The US Food and Drug Administration (FDA) has drafted a framework that outlines the potential manufacturing scenarios for 3D-printed devices in the medical field. Zang states that, “The FDA has established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialities referred to as panels. Each of these generic types of devices is assigned to one of three regulatory classes based on the level of control necessary to assure the safety and effectiveness of the device.”
However, the framework is very ambiguous. It doesn’t provide enough information on how regulations will apply to additive manufacturing facilities – both traditional and bioprinting. This brings questions as to whether clinicians will have a legal liability if they choose to print their own medical devices. For devices that are bought by hospitals from third parties, it’s not clear if the FDA will have the ability to oversee the full supply chain, as many sites (such as hospitals) are not typically regulated by the likes of the FDA. On top of that, the printers themselves are not regulated, as it is the manufacturing process and output that is regulated, which could lead to significant variation for each print – something that is not ideal for medical implants.
For bioprinting specifically, there has been no specific guidance issued by the FDA’s Center for Biologics Evaluation and Research (CBER) and it has not yet approved any bioprinted products. There needs to be more clear regulatory requirements for additive manufacturing in general for the medical industry before bioprinting regulatory guidelines get a look in. It may be that they all fall under the same regulatory umbrella, but they may not, and it will then take even longer to get regulations in place for bioprinted implants. There are, however, potential avenues that could be exploited for companies looking to bring bioprinted implants to market before firm regulations are in place. This is because there is an exemption for custom-made devices, which bioprinted implants would potentially fit into – as the exemption states that fewer than five should be manufactured and the device is being used to treat a condition that other medical devices cannot treat. In 2021, this pathway was exploited for a unique 3D-printed implant for treating a rare bone disease, but it remains to be seen if bioprinted clinical products will be able to take this route.
Overall, there is a lot of potential for improving patient outcomes at the point of care using bioprinted implants. While they are moving towards a clinical readiness, many challenges remain that makes it difficult to predict what the market penetration might look like in a few years – especially when the FDA and other regulatory bodies have not kept up with the rapidly growing pace of the additive manufacturing and bioprinting fields. The technology and capabilities are there – the rest just needs to fall into place.
3D bioprinting: A market on the rise
The global 3D bioprinting market is set to more than double by 2030, reaching an estimated $2.8bn, driven by investments in regenerative medicine and AI-enhanced printing. North America remains the dominant region, with leading players pushing innovation in multi-material printing and sophisticated bio-inks.
Emerging trends include the use of stem cells and organoids for drug testing. While costs and regulatory uncertainty remain hurdles, partnerships between universities and industry are accelerating progress. With clinical trials slowly moving from tissue models to implant applications, the market is poised to support a new generation of personalised, minimally invasive therapies.
Source: Markntel Advisors
