PROJECT SUMMARY/ABSTRACT Introduction: Skeletal Tissue Engineering Laboratories (STEL) Technologies, LLC is a woman-owned, Michigan- based regenerative medicine company founded in 2013. STEL’s first product, the CGEMTM graft, is a unique biological replacement for the anterior cruciate ligament (ACL) injuries. The researchers have since adapted this graft technology with the goal of treating Rotator Cuff (RC) injuries increasingly prevalent in the aging population. Significance: RC tears are a major orthopedic challenge in the US with over 460,000 surgeries performed annually resulting in a market cost of over $523M[1,46]. The failure rate of current RC repair procedures ranges from 20-95%, with a major contributing factor being the inability to restore native biomechanical properties at the enthesis, resulting in repairs characterized by a weaker, less organized fibrovascular scar tissue that is prone to failure[54]. Various tissue-engineering strategies are being developed to improve surgical outcomes and promote tendon healing, especially at the enthesis. Current approaches focus on the development of biological or synthetic scaffold devices to reinforce the mechanical strength of the tendon-to-bone connection, but they do not promote enthesis regeneration. There is significant demand for alternative technologies for RC repair. Vision for Commercial Product: The ETG-RC is devitalized allogeneic engineered multi-phasic tissue that regenerates the enthesis and provide an underlayment that allows the migration of endogenous cells, enhancing the regenerative capacity of the repair site. ETG-RC will lead to enhanced restoration of normal biomechanics and mobility, resulting in lower cost and decreased risk of re-injury and arthritis. An “off-the-shelf” tissue graft for RC repair will enhance the standard of care double row suture technique and deliver superior patient outcomes. Goals of Proposed Research: The goals of this SBIR Project are to establish the feasibility of fabricating a fully biologic “off-the-shelf” tissue-engineered rotator cuff tendon graft that can restore biomechanical properties of the tendon-humerus enthesis; and to de-risk the commercial viability of ETG-RC in order to advance the translatability of this technology for use in human patients. Specific Aims: The proposed project addresses the several pressing issues that must be resolved prior to bringing this technology to the FDA for clinical trials: development of a fabrication and decellularization protocol (Aim 1) and establishment of storage methods to determine shelf life (Aim 2). It then seeks to establish a master cell bank for fabrication of grafts for the Phase 1-3 clinical trials (Aim 3). CGMP quality ETG-RC grafts fabricated from the established master cell bank will be tested for safety and efficacy by NAMSA (Aim 4). Positive data from these studies will support filing of an IND-packet with FDA, enabling a Phase I clinical trial. Success of the SBIR project will r...