Bioengineering Priorities on a Path to Ending Organ Shortage

Abstract

This perspective article covers current successes in and continuing challenges remaining in eliminating the growing organ shortage. We specifically cover data from a workshop entitled BOrgan Bioengineering and Banking Roadmap Workshop^funded by the National Science Foundation (NSF) and the Methuselah Foundation in Washington, D.C. on May 27, 2015, and a subsequent Roundtable held at the White House Office of Science and Technology Policy (OSTP) on May 28, 2015. We address four parallel and potentially cooperative approaches for bioengineering tissues and organs. The first approach is bioprinting of tissues and organs. The second approach encompasses recellularization strategies, which can involve either developing tissue scaffolds from non-transplantable human (or xenogenic) organs or tissues and then reconstituting these templates with human cells to create a functional tissue/organ or seeding synthetic biodegradable scaffolds with human cells. The third approach is optimization of cellular repair and regeneration with strategies that include shifting the balance away from maladaptive processes that lead to chronic scarring. The fourth approach is xenotransplantation, which involves developing functional tissues for human use in transgenic animals whose cells are modified to prevent immune rejection. Current challenges and limitations are addressed, which include mapping, cell sourcing and manufacturing, immunosuppression, integration, and vascularization. We identify commercialization strategies that will make these approaches economically feasible. We present solutions toward a vision to one day ending the current organ and tissue shortage, and the impact this will have on treating disease and providing indirect economic benefit by decreasing the disease burden on society and improving quality of life.

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“…In this process, different cell types can be combined with various materials to form bioinks. Among the different types of cells, stem cells have made great attention because of their unique abilities in self-renewal and differentiation, as well as, their numerous applications in tissue engineering and regenerative medicine (2). Bioinks are used to fabricate scaffold-based (i.e., microcarriers, hydrogels and decellularized matrix components) or scaffold-free cell aggregates.…”

Stem cell bioprinting for applications in regenerative medicine

“…While some of these applications have gained U.S. Food and Drug Administration approval, including heart valve replacements, biopharmaceuticals, skin, bone, and cartilage wound repair, many applications use xenografts and decellularized scaffolds to provide the necessary architectural complexity . For many applications, the prevalence of graft rejection and the paucity of donor tissue demands an alternative approach . Accordingly, there has been a growing need to fabricate the microscale intricacies of 3D tissue organization, including cellular distribution and extracellular matrix (ECM) composition and structure .…”

“…Bioprinting can be defined as an additive manufacturing technique used to create cell‐loaded scaffolds, tissues, or tissue constructs . Specifically, this technique can print living cells encapsulated in bioinks to a prefabricated or simultaneously fabricated scaffold composed of synthetic polymers, natural biomaterials, and/or other biologics .…”

“…7 For many applications, the prevalence of graft rejection and the paucity of donor tissue demands an alternative approach. 10 Accordingly, there has been a growing need to fabricate the microscale intricacies of 3D tissue organization, including cellular distribution and extracellular matrix (ECM) composition and structure. 11 These fabrication demands have fueled a surge in the use of 3D bioprinting for applications in regenerative medicine.…”

“…12 Bioprinting can be defined as an additive manufacturing technique used to create cell-loaded scaffolds, tissues, or tissue constructs. 10 Specifically, this technique can print living cells encapsulated in bioinks to a prefabricated or simultaneously fabricated scaffold composed of synthetic polymers, natural biomaterials, and/or other biologics. [13][14][15] The capability of bioprinting techniques to prescribe micro-to macroscale architectures, comparable to in vivo tissue, has made these technologies particularly attractive for use in regenerative medicine ( Fig.…”