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.
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.
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).
Erik Gatenholm, Co-Founder and CEO, BICO
In terms of financial outlook, 3D System’s bioprinting-related activities do not yet represent a significant revenue generation segment however they are considered highly strategic. In its latest Q3 financial results, the company stated that “new opportunities for large-scale adoption of additive manufacturing opening before us, and entirely new markets being created in bioprinting, we believe we are very well positioned to deliver on our commitment to become a $1 billion revenue company in five years.”
Embracing the past and future of bioprinting
The final element in 3D Systems’ bioprinting strategy is to develop more complex biological structures and tissue engineering. This is where the acquisition of Volumetric Biotechnologies brought on significant tissue engineering expertise to expand the scope of human organ bioprinting efforts. The companies are now establishing a research facility in Houston, Texas to accelerate the development and commercialization of vascularized human tissues and bioprinted constructs for non-organ applications, and creating clear technological leadership in the rapidly emerging bioprinting field for laboratory applications including drug discovery.
When considering all the companies that are now part of the BICO group, there are as many as 11,000 instruments in the field, with most of these being bioprinters of various kinds (including 3D printers used for scaffolding in cellular cultures). Under bioconvergence, the lines between biology, engineering, nanotech, and data become increasingly blurred, allowing synergies to approach to biology as highly advanced engineering that’s been refined over billions of years. Within bioconvergence, Biosciences, provide user-friendly instruments to bring efficiency and speed to multiple application areas, such as cell line development, drug screening, and microscopy. Bioautomation accelerates the development and manufacturing of diagnostic and bioanalysis test platforms for patients, consumers, public health and the environment. Finally, Bioprinting enables printing with cells and biomaterials, creating tissues and organ-like structures that mimic physiological conditions.
Desktop Metal was founded in late 2015 with the stated objective of making metal additive manufacturing both more accessible (at first, via a bound metal extrusion process) and more scalable (via a metal binder jetting process). Six years later, these objectives have not yet been achieved but they are a lot closer. More importantly, many more bought into Desktop Metal’s vision including competitors, customers and – most importantly – investors, with the company raising over $2 billion after going public via a SPAC merger in late 2020.
On the one side, the company is targeting the expansion of bioprinting research at the academic level through its cost-effective CELLINK range of bioprinters (and gradually evolving to more advanced systems in its offer), feeding it with a wider range of bioink materials (obtained from the acquisition of Advanced BioMatrix).I personally find it fascinating seeing what researchers will do with it nextCarlos Carvalho, Team Leader Bioprinting Team at EnvisionTEC (now ETEC)
The ability to print large, vascularized, highly detailed hydrogel scaffolds at rapid speeds is opening new opportunities for a range of tissue applications. In addition, 3D Systems is developing bioprinting solutions that are both commercially viable and scalable from prototype to production.
Allevi’s newest desktop 3D bioprinters are versatile and easy to use, giving users access to a wide range of biomaterials—bioinks, bioink additives, cells, reagents and consumables—as well as an intuitive software interface.