Project Summary Healing following rotator cuff repair (RCR) remains a significant clinical challenge, and repair failure rates of 20- 30% continue to be reported. To date limited attention has been directed toward understanding how intrinsic mechanistic factors may contribute to variable healing rates following RCR. The objective of this proposal is to quantify the variability of the humeral head bone marrow in patients undergoing RCR and test the prognostic significance of the local concentration of connective tissue progenitors (CTPs) for tendon healing. Our approach will be to enroll 50 patients undergoing RCR. At the time of RCR, 8 ml of bone marrow will be aspirated from the humeral head for quantitative progenitor cell assays. A core biopsy at the tendon repair footprint will be collected for histologic analysis of bone marrow composition. Tendon healing will be assessed by MRI (Sugaya score) at 6 months follow-up, the timeframe in which majority of re-tears occur The variation of bone marrow characteristics among patients will be described (Aim 1) and their correlation with rotator cuff tendon healing will be investigated (Aim 2). The proposal seeks to shift the investigational paradigm to intrinsic patient biologic factors, a fundamental and under-investigated realm of potential prognostic factors of RCR healing. Demonstrating that humeral head characteristics associate with re-tear after RCR will support future work to develop tools to screen patient bone marrow for characteristics predictive of RCR success or failure and advance novel methods that promote local enrichment or transplantation of progenitor cells to augment RCR.