Regenerative rehabilitation: A call to action

Abstract

INTRODUCTION We have battled against disease since the beginning of time. As science and technology have evolved, so have the weapons in our antidisease arsenal improved. Indeed, in the last 50 years, the sheer volume of knowledge about human biology has doubled every 8 years. This means that the foundation on which the design and delivery of healthcare is built is 1,000 times stronger at the end of our lives than at the beginning. In the next century, we will add therapies that can restore lost function to ailing tissues and organs to the arsenal of health-aging technologies. This will eventually open the door to battling crippling diseases like diabetes, Parkinson, and heart failure, as well as the impacts of traumatic injury. Success in the laboratory, where all such endeavors must begin, will drive the commercial activities toward products that subsequently become available to patients. Regenerative medicine is multidisciplinary field incorporating expertise from engineers, biologists, and chemists, to name few. The goal of regenerative medicine is to restore tissue and organ function lost as result of aging, injury, or disease. It uses variety of tools to divert the default pathways of wound healing in humans, which typically result in patchwork of scar tissue, toward pathways that recapitulate restoration of original tissue/organ architecture and function. Regenerative medicine scientists seek to harness tissue and organ regeneration that was once only possible as fetus or newborn. We believe that rehabilitation science and technology will be critical in the success of any regenerative therapy and therefore the two fields must pay increasingly more attention to each other. We suggest herein variety of mechanisms for the rehabilitation community to be the enablers of regenerative therapies. Because regenerative therapies are outcome-driven rather than technology-specific, the community needs to engage in this interdisciplinary cross-fertilization with an understanding of the different tools that can be used to restore lost organ and tissue function. Our ability to restore damaged tissues and organs today relies on three large categories of interventional approaches: (1) medical devices/artificial organs, in which tissue function is replaced with entirely synthetic constructs and machines; (2) tissue engineering and biomaterials, in which temporary scaffolds are used to bridge large tissue-gap defects; and (3) cellular therapies, including the transplantation of stem cells and genetically manipulated cells for the repair of damaged or diseased tissue. The Figure illustrates the concept of vertical integration of rehabilitation and regeneration. Traditionally, regenerative medicine and rehabilitation have existed as serial processes in patient treatment and care plans, despite common end points. In contrast, we propose that the vertical integration of rehabilitation and regeneration, in which the two tracks are fused at the onset of therapeutic development, will allow us to achieve functional goals faster and more effectively. Conjoined education in these disciplines must be the vehicle through which each field can learn where the overlaps exist and how to exploit opportunities. [FIGURE OMITTED] Here, we provide an example of how the treatment of skeletal muscle injury could be affected by regenerative medicine and optimized by regenerative rehabilitation. TREATMENTS TO PROMOTE SKELETAL MUSCLE REGENERATION FOLLOWING ACUTE INJURY Muscle injury, defined as a prolonged impairment of the ability of muscle to produce force [1], can greatly impair an individual's function and ability to participate in recreational and occupational activities. The four interrelated phases of healing, irrespective of the cause of injury, have been well characterized in both animals and models and consist of degeneration, inflammation, regeneration, and fibrosis (reviewed by Huard et al. …