Mitochondria as a therapeutic: a potential new frontier in driving the shift from tissue repair to regeneration

Fibrosis, or scar tissue development, is associated with numerous pathologies and is often considered a worst-case scenario in terms of wound healing or the implantation of a biomaterial. All that remains is a disorganized, densely packed and poorly vascularized bundle of connective tissue, which was once functional tissue. This creates a significant obstacle to the restoration of tissue function or integration with any biomaterial. Therefore, it is of paramount importance in tissue engineering and regenerative medicine to emphasize regeneration, the successful recovery of native tissue function, as opposed to repair, the replacement of the native tissue (often with scar tissue). A technique dubbed 'mitochondrial transplantation' is a burgeoning field of research that shows promise in in vitro, in vivo and various clinical applications in preventing cell death, reducing inflammation, restoring cell metabolism and proper oxidative balance, among other reported benefits. However, there is currently a lack of research regarding the potential for mitochondrial therapies within tissue engineering and regenerative biomaterials. Thus, this review explores these promising findings and outlines the potential for mitochondrial transplantation-based therapies as a new frontier of scientific research with respect to driving regeneration in wound healing and host-biomaterial interactions, the current successes of mitochondrial transplantation that warrant this potential and the critical questions and remaining obstacles that remain in the field.