The new “Big Three” of the 3D bioprinting industry

This indicates a vibrant and lively community, which however is still very much relying on university research and academic adoption, since commercial applications of bioprinting remain limited to early development and testing. These are currently intended as either cosmetics testing or drug development & testing (DDT). Production applications, much like in most industrial 3D printing, remain a mirage mostly due to challenges in terms manufacturability (for organs and tissue grafts) and scalability (in the case of tissues and for the rapidly  emerging area of cellular agriculture/3D printed lab-grown meat applications).

For more than three decades, 3D Systems created new approaches and processes for product development, parts manufacturing and personalized healthcare through additive manufacturing solutions. The company owns patents for multiple different additive manufacturing technologies, including metal and polymer processes used in the orthodontic and orthopedic implant industries – which share several aspects with bioprinting processes and applications.

Today Allevi can be considered a leading innovator in the bioprinting space with an exclusive focus on the research and development community. Leading laboratories leverage Allevi’s portfolio of hardware, biomaterials and software to design, engineer and build solutions for tissue engineering, organ-on-a-chip research, pharmaceutical validation, biomaterial development, and regenerative medicine.

More existing collaborations, with CollPlant Biotechnologies and Antleron, also expand the capabilities in regenerative medicine research and development solutions, as 3D Systems continues to seek partners with the same mission of transforming healthcare through groundbreaking technologies.

3D Systems officially entered the bioprinting segment by acquiring startup company Allevi, which attempted to do something similar to CELLINK (in fact it was one of the very first to launch a low-cost bioprinter) but with less effective results. Instead of starting from materials to progressively expand into hardware, like CELLINK, Allevi (which at the time was called BioBots), started from the hardware and had a more difficult time in establishing a significant installed base. The company went through some changes in management, including the name change to Allevi, and was finally acquired by 3D Systems in May 2021, making it into one of the foundations to its new bioprinting business.

The next step in 3D Systems’ bioprinting strategy focuses on the company’s wide experience in the medical devices and implant segments. To date the company produced more than 2,000,000 serial component medical devices and 140,000 patient-specific surgical cases: now it’s looking to scale the production of bioprinted clinical applications, leveraging and adapting existing technology (which can almost seamlessly be used for scaffolding) to elevate patient care through various clinical applications, ranging from acellular bioresorbable devices to functionalized solid organs for transplantation.

BICO’s mission is to enable the pharmaceutical and biopharma industries to develop new drugs faster and safer, with more specificity and less need for animal testing. The company’s strategy until recently has been to acquire innovative technology companies once they are de-risked and ready for commercialization and scaling up. After some challenges, the group now seems well-positioned for rapid growth, as a leading provider of drug discovery and drug development tools. This is a similar strategy to the one pursued by Organovo, with failing results. However, BICO is operating at an already much larger level in terms of revenues and available technologies, with more cost-efficient and accessible tools which are already generating important returns. Organovo was a pioneer but it may have entered the bioprinting market too early.

Together with United Therapeutics Corporation and its organ manufacturing and transplantation-focused subsidiary, Lung Biotechnology PBC, 3D Systems achieved significant progress in the development of next-generation bioprinting solutions for lung scaffolds that are capable of full-size, vascularized, rapid, micron-level printing.

When we began to track the 3D bioprinting market nearly a decade ago there were less than a dozen companies operating specifically in this segment as commercial entities, with most development taking place at the academic level. Today, 3dpbm’s 3D Printing Business Directory’s Bioprinting section lists 133 entities, of which 47 are hardware (bioprinter) manufacturers, 41 are material (bioink) suppliers and 59 are considered service providers (a category that includes bioprinting laboratories at universities).

The 3D-Bioplotter bioprinters can process open-source biomaterials using air or mechanical pressure to a syringe, which can fabricate scaffolds to create tissue, with X-Y repeatability down to 1 μm. All models have been designed for use in a sterile biosafety cabinet, meet standards for clinical trials and offer build sizes up to 192.4 cubic inches.

The natural evolution of this aspect of 3D Systems’ strategy is to implement advanced bioprinting technology development to meet the evolving needs of the clinical and R&D communities. Here, the trademarked Print to Perfusion process enables 3D printing of high-resolution scaffolds, which can be perfused with living cells to create tissues.

Since BICO is the only public bioprinting (almost) pure player (after Organovo collapsed and exited the segment), its public financial results and publicly disclosed strategies are a good indicator of bioprinting’s overall health. BICO’s long-term and mid-term goals are to reduce the organ shortage and speed up drug development by providing accessible life science solutions that combine biology and technology. The concept of bioconvergence, which inspired the company’s name, refers to using a combination of robotics, artificial intelligence, advanced genomics, and 3D bioprinting, to create new healthcare solutions.

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The Big Three bioprinting companies are each targeting these areas from different angles that they considered strategic.

Bioconvergence for commercial applications

The system uses modular components, such as sterilized heating and cooling cartridges, standard Luer-Lok syringes with standard needle-tip sizes and an easy-to-use 365 nm UV curing head. “It’s a popular tool because it’s a very flexible, but also user-friendly machine,” Carlos explained. The software also allows for maximum freedom in combining different materials using different temperatures.

BICO’s acquisition phase was very rapid (over a period of just about 2 years), and the result is a highly diversified product offering, which limits technical risks. In several cases, these technologies fundamentally change the way laboratories work, implementing new and efficient workflows to automate operations. Many of these solutions are the results of synergistic work from several of BICO’s companies working cooperatively. Examples include customizable MatTek Dishes combined with the ECHO Revolve hybrid microscope for easy to use, universal compatibility with laboratory equipment, built-in glass coverslip for ultraclear imaging, no messy or fragile slides, and customized options to suit cell culture and/or imaging objectives. Another is the G.STATION NGS, developed in collaboration between Dispendix, Cytena and Qinstruments to provide automated workflows for next-generation sequencing. Finally, Bionova, the first digital light processing (DLP) based bioprinter for direct printing in multi-well plates, combines technologies from Allegro 3D, Cellink and Advanced BioMatrix. It prints functional tissue models in seconds with superior resolution, speed and reproducibility. It also accelerates research by providing biomimetic models for regenerative medicine, precision medicine and disease modeling.

Recently 3D Systems also launched Systemic Bio, a fully owned company based in Houston, Texas, focused on the development of vascularized organ models made out of hydrogels and human cells to be used for drug discovery and development. With a state-of-the-art laboratory and a team of bioengineering experts, Systemic Bio is pushing the boundaries of preclinical drug testing. Its proprietary platform is built with production-level 3D Systems technology, which has a greater build volume and a higher resolution than most commercially available technologies.

Today – at this point in time – we can take this step in regenerative medicine to influence the future of mankind.Chuck Hull, Founder of 3D Systems and inventor of 3D printing (stereolithography).

Given the change in the macroeconomic environment, we [BICO] have a firm focus on profitability and cash flowErik Gatenholm, CEO, BICO

All these are based on the development and introduction of both bioprinting-specific materials and general healthcare 3D printing materials. The 3D-Bioplotter platform uses Hydrogels & Cells designed to be both biocompatible and cell-friendly, capable of supporting a variety of applications in bone regeneration, cartilage regeneration, soft tissue fabrication, drug release, and organ 3D printing. Other 3D-Bioplotter supported materials include Ceramics, which is bio-active, osteoinductive and osteoconductive materials that are designed to promote bone growth in the implantation area. These are used in critical size defects as bone grafts with complex inner patterns that mimic the surrounding bone’s mechanical properties, and as custom ceramic implants in maxillofacial applications. The overall healthcare strategy also includes Photopolymers (for immediate medical device fabrication), Metals (for surgical tools, prosthetics, splints and implants) and Thermoplastics (for cartilage regeneration applications, such as knee meniscus or trachea defects).