The use of orthobiologic treatment strategies in the augmentation, regeneration, and repair of tendon, nerve, muscle, and bone injuries in the upper extremity is an area of intense research and development. A recent survey of members of the American Medical Society for Sports Medicine revealed that 66% are using at least one orthobiologic in their practice and 72% are increasing their use, although preclinical and clinical evidence for the efficacy of these treatment strategies is at various stages. Here, the current state of orthobiologic treatment strategies in the upper extremity is summarized and future research opportunities are discussed.

Despite improvements in surgical techniques for rotator cuff repair, retear following repair remains a common clinical occurrence. Orthobiologic treatment strategies have aimed to provide more consistent postoperative healing and improve outcomes. Among orthobiologics, platelet-rich plasma (PRP) has emerged as a promising augmentative therapy in rotator cuff repair in several prospective clinical trials; however, future clinical trials using standardized PRP preparations and a comparison cohort of placebo injections will be necessary to fully evaluate the efficacy of PRP. In addition to PRP, biologic and synthetic grafts are currently being used to augment repairs at the time of surgery by supplying a structural scaffold to enhance healing. The current literature suggests that at least some grafts may serve to reduce retearing after rotator cuff repair, but these reports are generally from small retrospective cohorts without controls or long-term follow-up. Without strong clinical evidence of a clear benefit of graft augmentation, which will require prospective randomized controlled trials with clinical and structural outcomes, the cost and added surgical time to apply are likely to limit the use to specific indications such as massive cuff tears. Cellular therapies such as tissue-specific activated endothelial cells, bone marrow-derived progenitor cells, and adipose-derived progenitor cells have recently emerged as potentially promising therapy modalities in preclinical models. However, because animal models do not recapitulate the complex etiology and variable presentation of rotator cuff disease, their safety and efficacy need to be further evaluated using translational studies and prospective clinical trials in humans.

Tendinopathy is a complex and multifaceted clinical disorder resulting in limb pain and disability. Highly effective treatment strategies remain elusive because the pathophysiology of tendinopathy is poorly understood, being multifactorial and clinically heterogeneous. Mechanical microtrauma or macrotrauma, hypovascularity, genomic variations, imbalance of neurogenic input, extracellular dysfunction, immune disturbances, and metabolic conditions may all contribute to varying degrees to the onset and/or progression and persistence of tendinopathy that presents itself in the clinic. Orthobiologic treatment of chronic epicondylar tendinopathy, gluteal tendinopathy, and plantar fasciitis using leukocyte-poor PRP has shown clinically meaningful improvements in pain and functional scores in level I studies. More work needs to be done to confirm the value of leukocyte-rich PRP or other formulations for other tendinopathic conditions. Other cellular and acellular biologics such as bone marrow aspirate concentrate and adipose-derived injections are currently under investigation for treating tendinopathy but presently lack enough supporting evidence to recommend wide
clinical use. Exercise may also be considered an effective biologic treatment and should be further investigated. Ultimately, understanding the biologic mechanisms of tendinopathy would increase the potential for more precise and effective treatment for this painful and debilitating condition. Because there are very limited animal models of naturally occurring tendinopathy, mechanistic studies are likely to require systematic and deep investigation of tendinopathic tissues biopsied from patients with these conditions.