Biofabrication on the Cusp of Mass Production
A new paradigm in manufacturing is steadily growing thanks to partnerships among academics, industry leaders, and government entities. In laboratories across the globe, breakthroughs in the engineering of biomaterials are giving glimpses into the future of regenerative medicine, which is a means of treating disease and saving lives that harnesses the power of the body’s ability to heal itself and marries it to cutting-edge technology. As the healthcare and manufacturing industries combine their powers to address a mounting global health crisis, the line between science fiction and science fact is blurred for the benefit of everyone.
An Ever-Increasing Demand for Organ and Tissue Donations
It wasn’t long ago that tissue and organ transplantations were considered medical breakthroughs. According to the U.S. Department of Health and Human Services, the first transplant of skin occurred in 1869 and the first transplant of a solid organ – a kidney – took place in 1954. In the ensuing decades, the demand for replacement body parts increased dramatically in the U.S., yet the supply has not kept pace with it. In 2006, the Institute of Medicine (IOM) published a book titled “Organ Donation“ which put forth recommendations for increasing the availability of donated organs. Despite heightened public awareness and the efforts of organizations such as the Organ Procurement and Transplantation Network (OPTN), the gap between those in need and those who can provide continues to widen. It is in this space that advances in regenerative medicine and the emerging technologies that make up biofabrication are poised to save countless lives.
The Path Forward via Regenerative Medicine
Organ transplantation is a technique within the field of regenerative medicine, which also encompasses the application of biochemical techniques to induce tissue regeneration, as well as the use of differentiated cells (e.g. stem cells) either alone or as part of bioartificial (i.e. engineered) tissue. Ideally, a patient’s own cells are used to avoid the complications associated with immune system rejection. Use of another person’s organs, tissues, or cells requires an extensive matching process, as well as administration of immunosuppressive drugs to curb the rejection risk. Research efforts in the realm of regenerative medicine are evolving new technologies and techniques for providing patients with desperately needed tissues and organs, yet the pathway to mass production has not been straightforward. Until now.
The next step on the path to bringing regenerative medicine to the masses is through the process of biofabrication.
What is Biofabrication?
Biofabrication is a type of manufacturing – also referred to as biomanufacturing – that combines the disciplines of mechanical engineering, biomaterials science, cell and developmental biology, computer science, and materials science, to name a few. It involves the creation of complex biological products from raw materials such as living cells, biomaterials, extracellular matrices, and molecules. In the context of addressing the need for donated tissue and organs, biofabrication can create safe and effective products from a patient’s own raw materials, therefore reducing the chances of rejection by their immune system. So far, the majority of the work in biofabrication has taken place in laboratories, and output has been limited. The great challenge is scaling biofabrication to a level at which manufacturing output can meet demands while maintaining compliance with U.S. FDA regulations.
All of the technologies that are emerging as part of the Fourth Industrial Revolution, including big data analytics, autonomous robots, simulation, horizontal and vertical system integration, the Industrial Internet of Things (IIoT), cybersecurity, the cloud, additive manufacturing, and augmented reality, will be utilized and pushed to new limits in the service of scaling biofabrication. Global businesses have been investing in these technologies for the sake of advancement in their respective markets, and now is a tremendous opportunity to use these capabilities in partnership with medical research entities and government entities to save lives.
BioFabUSA Creates a Multidisciplinary National Consortium
According to Dean Kamen, a world-famous inventor and the president of DEKA Research & Development, “There have been significant breakthroughs in cell biology, biofabrication, and materials science in the last decades, which have laid the foundation for large-scale manufacturing and commercialization of engineered tissue-related technologies, including tissue and organs. Now it is time to move out of the lab and into the factory.”
To jump-start this effort, the United States Department of Defense (DoD) in 2016 awarded $80 million in federal funding to the Advanced Regenerative Manufacturing Institute (ARMI) for the establishment of an Advanced Tissue Biofabrication (ATB) Manufacturing USA Institute. This program, known as BioFabUSA, is a made up of 47 industrial partners, 26 academic and academically-affiliated partners, and 14 government and non-profit partners. Its mission and purpose are to “help others with whatever they need to create the product be it knowledge, technology, equipment, process, and standards – anything needed to address the ecosystem for a new industry,” explains Kamen. His organization, FIRST, is one of BioFabUSA’s non-profit partners.
Scaling the advances in regenerative medicine to meet public health demand, and in the process growing a brand new industry, requires a multidisciplinary approach with an emphasis on scalability. The scope of BioFabUSA’s efforts will focus on five so-called thrust areas:
- Cell selection, cell culture, and cell scale-up
- Biomaterial selection and biomaterial scale-up
- Tissue process automation and process monitoring
- Tissue maturing technologies
- Tissue preservation and tissue transport
With high ambitions, BioFabUSA plans to not only advance biofabrication to new heights but also to provide educational opportunities for rising and existing workforce talent, in the hopes of heading off the inevitable skills gap that will be created by rapid technological advancements. Due to the multidisciplinary nature of large-scale biofabrication, these opportunities will need to cover a broad spectrum of disciplines, from computer science to life science and beyond. Minding the skills gap while building the biofabrication industry is not only smart, it is imperative.
Printing Kidneys at Scale
Dean Kamen acknowledges that “it takes a force of nature to move an idea from the lab to the factory. With collaboration among the members of ARMI/BioFabUSA, we feel there will be significant breakthroughs in the next five to ten years – maybe sooner. Imagine how healthcare would change if we could print a new kidney or liver for you when you needed one.” As it turns out, this statement is far from conjecture.
Harnessing the power of additive manufacturing, which is also known as 3D printing, companies are beginning to see success in creating functioning biomaterial that can replace complex body parts, including kidneys. To get there, however, requires the perfection of the techniques and technologies needed to create the tiniest of biological structures, namely capillaries and specialized cells. Success requires a multifaceted approach, and mass production is the end game. A white paper published by Prellis Biologics, a small startup and alumnus of the IndieBio Accelerator program in San Francisco, CA, identifies four requirements for 3D printing functional human organs at scale:
- Resolution: The ability to create tissue, organs, and extracellular matrix, needs to fall within the range of a single cell, which is between one to ten microns.
- Speed: Printing times must be compatible with the health of the cell structures being printed, which posses unique sensitivities and lifetime constraints.
- Complexity: Engineered tissue needs to match the complex structural components of the living tissue it is intended to replace, and be capable of providing nuanced functionality.
- Biocompatibility: The product must be compatible with the patient’s immune system, be structurally sound, and capable of operating within the physiological requirements of a natural organ.
Co-founder Melanie Matheu, a research scientist interviewed by TechCrunch, estimates the global tissue engineering market will grow from $23 billion in 2015 to $94 billion by 2024. Though the work at Prellis is aimed at printing kidneys, the innovations achieved through the company’s efforts are applicable throughout the field of biofabrication. The promise of lowering health care costs and saving lives worldwide is within reach.
Work with a High Purpose
Dave Vasko, director of Advanced Technology at Rockwell Automation, an industry partner in the BioFabUSA program, explains “As quickly as the possibilities are unfolding, the advances largely are still in the research mode. The good news: While the recipes are incredibly specialized, the process of regenerative medicine manufacturing looks a lot like something you’d see in the making of a craft beer – automating the process and using data and analytics to monitor and improve that process to create consistent predictable results.” Through collaborative efforts like those of BioFabUSA, as part of the greater Manufacturing USA institute network, printing kidneys in a cost-effective manner at scale will soon become a reality.
The business of saving lives may be complex, but it need not be daunting. Thanks to proactive investments by entities and individuals, a burgeoning technological landscape ripe for disruption, and the power of human good will, regenerative medicine is being given a massive platform to transform healthcare at scale and bolster the global economy with the addition of new industry. Dave Vasko said it best: “This is work with a high purpose.”