Jeremy Mercuri, Ph.D.
Assistant Professor of Bioengineering
Point of Care Regenerative Medicine – Rotator Cuff Engineering in the Operating Room
Due to intrinsic and extrinsic factors, the tendons connecting the shoulder muscles to the humerus (i.e. the rotator cuff - RC) become torn and commonly cause shoulder instability, weakness, pain and may ultimately result in osteoarthritis. This damage poses a significant challenge to repair and despite advances in surgical technique, clinically successful outcomes amongst patients with massive RC tears are variable and re-tears remain a challenging problem. Torn tendons account for nearly 4.5 million physician visits and 300,000 surgical procedures annually in the U.S. resulting in an estimated total cost of $3 billion. Large and massive tears (i.e. those exceeding 3-5 cm in anterior-posterior length and involving two or more tendons) account for 12%–40% of all RC tears. Using suture to secure torn tendons back to their original humeral insertion is the standard of care; however reinforcement of large and massive tears with tissue grafts or other biologics are typically warranted. The majority of commercially available grafts cleared by the U.S. FDA are derived from xenogenic or allogeneic sources. While utilization of these grafts has been shown to reduce re-tear rates, the potential for immune rejection and infection are ever-present. Early investigations into the incorporation of biologics for RC repairs including growth factors, stem cells or tenocytes have illustrated promise; however increasing scrutiny by the U.S. FDA in regards to pre-market approval routes of such technologies add significantly to the cost and time required for the development and delivery of such products.
In order to address these hurdles, we believe an effective translation of these cell- and tissue-based therapies from bench-top to bedside requires a safe and innovative approach. In conjunction with our clinical collaborators, we propose to develop a point-of-care technique for tendon regeneration utilizing the patient’s own tendon tissue and stem cells to make an autologous engineered construct for use as a biologic adjunct to suture repair. More specifically, the goal of this project is to construct a biological patch during RC surgery in the operating room that can be incorporated within the suture repair. It will consist of; 1) a scaffold derived from an autologous tendon graft that will be manufactured into a porous scaffold using common surgical instrumentation and 2) autologous adipose derived stem cells (ADSCs) obtained from the stromal vascular fraction of centrifuged lipoaspirate. This stem cell seeded patch will be incorporated into a suture repair using techniques commonly employed for RC tissue grafting. It is hypothesized that this autologous composite will improve tendon healing due to the biomimetic nature of the scaffold containing intrinsic instructional cues and its ability to deliver and induce tenogenic differentiation of stem cells, thus directly contributing to new tendon matrix production. Initial studies are under way in order to illustrate the basic proof-of-concept of our novel and innovative approach.
The proposed research represents an effective translational approach to tendon regeneration that may contribute to reducing the incidence of re-tears in patients with massive RC tears which being manufactured and utilized by surgeons at the point-of-care. Furthermore, if proven successful similar approaches may be developed for use in other tissue regeneration applications thus potentially accelerating the clinical adoption of tissue engineering therapies.