The role of the subacromial bursa in rotator cuff degeneration and healing

ABSTRACT Rotator cuff degeneration results in shoulder pain and disability and a high incidence of rotator cuff tears. More than half of the population over the age of 65 has a rotator cuff tear, leading to ~600,000 surgical repairs each year in the United States. Unfortunately, the failure rates after surgical repair are unacceptably high, particularly in the older patient population with large tears. This project focuses on the subacromial bursa, a synovial-like tissue in the shoulder that is situated between the acromion and the rotator cuff tendons. This tissue was previously thought to function as a mechanical cushion and low friction gliding surface to protect the underlying tendons. The belief that the bursa is biologically inert motivated the current clinical standard of surgically removing the bursa in many scenarios. Contrary to this practice, our global hypothesis is that the subacromial bursa is a critical paracrine regulator of shoulder health with important roles in rotator cuff pathology and healing. Furthermore, due to its location above the rotator cuff, the bursa is an ideal therapeutic target for modulating rotator cuff degeneration and enhancing repair. In Aim 1, the role of the subacromial bursa in rotator cuff tendon degeneration and healing will be examined. We hypothesize that bursectomy will exacerbate rotator cuff degeneration of intact tendons and impair healing in models of rotator cuff tendinopathy. In Aim 2, patterns of cellular crosstalk between the subacromial bursa and the rotator cuff will be interrogated. We hypothesize that rotator cuff tendinopathy will activate the bursa through paracrine signaling, leading to recruitment of inflammatory cells and expansion of resident mesenchymal stem cells in the bursa. In Aim 3, the therapeutic potential of targeting the subacromial bursa for improving rotator cuff healing will be determined. We hypothesize that inhibition of inflammatory signaling in the bursa will shift bursa-derived paracrine factors from inflammation- dominant to regeneration-dominant, leading to enhanced rotator cuff healing. The project will lead to novel bursa- targeted pharmacologic therapies for rotator cuff repair, addressing the pressing clinical need to improve outcomes after rotator cuff repair.