Regenerative medicine: Current therapies and future directions

Abstract

Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.

Keywords: biomaterials; regenerative medicine; review; tissue engineering.

Fig. 1.

Regenerative medicine strategies that recapitulate tissue and organ structure. (A) Scanning electron microscopy image of a TEVG cross-section. Reproduced with permission from ref. . (B) Engineered bladder consisting of a polyglycolide and collagen composite scaffold, fabricated based on CT image of patient and seeded with cells. Reproduced with permission from ref. . (C) CT image of bone regeneration in critically sized defects without (Left) and with (Right) nanofiber mesh and alginate scaffold loaded with growth factor. Reproduced with permission from ref. . (D) Small hydrogel building blocks are assembled into tissue-like structures with microrobots. Reproduced from ref. , with permission from Nature Communications. (E) Blueprint for 3D bioprinting of a heart valve using microextrusion printing, with different colors representing different cell types. (F) Printed product. Reproduced with permission from ref. . (G) Intestinal crypt stem cells seeded with supporting Paneth cells self-assemble into organoids in culture. Reproduced from ref. , with permission from Nature.

Fig. 2.

Strategies for vascularizing and innervating tissue-engineered graft. (A) Tissue-engineered graft may be vascularized before implantation: for example, by self-assembly of seeded endothelial cells or by host blood vessels in a process mediated by growth factor release. Compared with bolus injection of VEGF and PDGF (B), sustained release of the same growth factors from a polymeric scaffold (C) led to a higher density of vessels and formation of larger and thicker vessels. Reproduced from ref. , with permission from Nature Biotechnology. (D) Scaffold vascularized by being implanted in the omentum before implantation at the injury site. Reproduced with permission from ref. . (E) Biodegradable microfluidic device surgically connected to vasculature. Reproduced with permission from ref. . Compared with blank scaffold (F), scaffolds delivering VEGF (G) increase innervation of injured skeletal muscle. Reproduced from ref. , with permission from Molecular Therapy.

Fig. 3.

Illustrations of regenerative medicine therapies that modulate host environment. (A) Injected cells, such as MSCs, can release cytokines and interact with host cells to induce a regenerative response. (B) Polyethylene glycol hydrogel (green) conformally coating pancreatic islets (blue) can support islets after injection. (Scale bar: 200 μm.) Reproduced with permission from ref. .