On a mission to create a human lung using living cells, 3D Systems acquired two up-and-coming 3D bioprinting companies, Allevi and Volumetric, in 2021. Notably, these innovations and transactions are hardly outliers. Within the past five years, there has been marked development in the 3D bioprinting space, with mergers, acquisitions, and fundraising activity in full swing alongside rapid technological advancement.
3D Bioprinting Technology
Given the complexity of 3D bioprinting, each element of the tech stack—including the bioprinter, the bioink, and the software—plays a critical role in the success of the desired construct. There are four main types of bioprinters on the market, with key variations across speed, manual processing, precision, cell viability, and bioink requirements. Inkjet printing paved the way from traditional plastic 3D printing to 3D bioprinting in 2003 but has since been largely replaced by more advanced technologies. Among these is extrusion-based bioprinting, which is another nozzle-based technique. Although popular for its affordability and relatively high precision, this technique is limited by viscosity-based bioink requirements and risk of low cell viability. If extrusion-based bioprinting is considered an approachable technique with average quality measures, laser-based bioprinting occupies the opposite end of the spectrum. This technique enables the highest level of precision and cell viability among bioprinting options but is generally not considered scalable due to the manual effort required.
Treading the line between scalability and quality, digital light processing stereolithography (DLP SLA) has emerged as an increasingly popular bioprinting technique that offers high precision and cell viability at a commercial speed and scale. High precision bioprinting will be integral to the future achievement of complex constructs by, for example, allowing for vasculature down to the arteriole level. Furthermore, multi-material bioprinting is likely to prevail within the DLP SLA field by enabling mixed-composition constructs.
Unlike direct-to-consumer plastics 3D printing, whereby materials and software are commoditized and can be used across printer and model types, bioinks and software for 3D bioprinting are often proprietary to each individual company. While bioink retail companies exist, 3D bioprinting companies with advanced capabilities typically create their own formulation. Similarly, most companies design their own proprietary modeling software. Given the high degree of precision required for 3D bioprinted models and the relative nascency of the field, commoditized bioinks and software risk being too generalized to accomplish the complex goals of each application.
The preclinical stage of pharma drug development bridges the gap between drug discovery and clinical research. While this phase of development is dedicated to identifying viable drug candidates, current preclinical methods—namely in vitro cell models and in vivo animal models—all too often fail to produce findings that translate into the clinic. Studies highlight staggering clinical trial failure rates of around 90%, largely due to efficacy and toxicity factors that were not predicted by preclinical models (1-3). Evidencing the stark need for alternative, cutting-edge solutions, the 2022 FDA Modernization Act 2.0 specifically included bioprinted models as an option for nonclinical tests. In turn, pharma has been increasingly partnering with 3D bioprinting companies to create cell-derived models that accurately replicate the 3D environment of interest, thereby promising translatable insight across dosing, toxicity, and efficacy to guide candidate selection.
In addition to advancing preclinical pharma research, 3D bioprinting promises to revolutionize the clinical care space. Innovations in personalized regenerative and transplant medicine remain an urgent and unmet need in the healthcare system, from tissue grafts to complex organ transplants. For example, there are currently 105,372 patients in the U.S. waiting for lifesaving organ transplants (4). Technological advances in 3D bioprinting continue to increase the level of organizational complexity achievable with living cells, from skin grafts to liver nodules to, eventually, complex organs. Concurrently, the FDA has demonstrated increasing willingness to usher 3D bioprinted solutions into the clinic. For example, 3DBio—the first and only clinical-stage 3D bioprinting company to date—received FDA rare pediatric disease designation for their patient-derived ear reconstruction implant in 2019, which is currently in phase 1/2a clinical trials. Several other companies have reported promising preclinical animal studies for 3D bioprinted solutions ranging from cartilage, to breast, to liver.
Although some companies focus primarily on preclinical research and others solely on clinical care, many companies harness preclinical research as a gateway into clinical care. 3D bioprinting companies that operate in this middle ground are well-positioned to capitalize on near-term opportunities in preclinical research while developing the technology and FDA traction necessary to enter the clinical care space. Companies focused primarily on preclinical models have a considerably lower ceiling for growth than the clinical care market, while companies focused primarily on clinical care miss out on a sizeable revenue opportunity as they work to overcome the obstacles to in-patient use. Lastly, companies that solely commercialize their bioprinting technologies instead of harnessing them internally for these applications will have a relatively limited impact on the long-term healthcare market.
3D bioprinting will not only transform the preclinical research space, but it will completely revolutionize clinical care by meeting the urgent need for personalized, life-saving interventions. Significant and continuing developments in technology and FDA regulation—from partnerships and acquisition activity to a clinical-stage 3D bioprinted ear implant—indicate that, although complex organs have yet to be achieved, they are near on the horizon. Importantly, preclinical research provides a revenue opportunity that mitigates the risk of obstacles that delay in-patient use. At the cusp of exponential growth in both the preclinical research and clinical care sectors, the 3D bioprinting market is optimally positioned for a high return on investment.
Seyhan A. Lost in Translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles. Trans Med Com. 2019
Akhtar A. The Flaws and Human Harms of Animal Experimentation. Camb Q Health Ethics. 2015.
Mullard A. Parsing clinical success rates. Nat Rev Drug Disc. 2016.