Introduction: STEL Technologies, LLC is a Regenerative Medicine company founded in April 2013. The founders STEL are researchers at the University of Michigan. STEL's first product, the CGEM? graft is an innovative and paradigm-shifting approach to ligament tissue engineering and a unique biological replacement for the anterior cruciate ligament (ACL) injuries. Significance: More than 350,000 ACL reconstruction surgeries are performed each year in the U.S. [1]. In addition to the high cost of the procedure, these patients are at high risk of developing osteoarthritis (OA) within a decade after surgery. With the increase in pediatric ACL injuries, the long-term costs and quality of life implications will be an increasing healthcare issue until improvements in treatment are developed [2]. The current state-of-the-art in torn ACL management is either non-surgical, conservative treatment or surgical repair. The current grafts used for repair don't restore normal function; early onset OA remains a risk and is seen in about 37% of treated cases.2 Product: The CGEM? (cell-generated matrix) graft is a devitalized allogeneic tissue-engineered combination tissue produced from differentiated bone marrow derived mesenchymal stem cells (MSCs) and assembled in a proprietary semi- closed 3D tissue production system. The unique compositional and mechanical properties of the CGEMTM graft allow the patient's body to regrow native ACL tissue that results in: 1) a reduced incidence of short-term graft failures (<2 months post surgery); 2) improved knee stability at 6 months (measured by joint laxity and clinical evaluation); and 3) improved knee function at 6 months (evaluated by gait and muscle function). The CGEMTM graft can restore near normal form and function to an ACL injured knee and eliminate the donor site pain and disability associated with autografts and graft failure risks associated with allografts. In implantation studies of these constructs in sheep, the graft achieves 100% success in spanning the native ACL site and integrating with native bone. Goal: This Phase 2 SBIR proposal will continue the success of our Phase 1 STTR towards developing our CGEM? graft fabrication methodologies to obtain a product suitable for human use. The development of the product lies in three areas and will comprise the three aims of this current proposal presented below.
Aim 1 : To scale-up the CGEM? graft to a size applicable for adult humans and confirm comparability of preclinical sheep-derived grafts with clinical CGEM? graft.
Aim 2 : To confirm the identity, potency, quality, purity, and sterility of the clinical CGEM? graft with the ultimate goal of defining the release criteria for the clinical CGEM? graft.
Aim 3 : To characterize a Master Cell Bank for the clinical CGEM? graft. Expected Outcomes: Confirmation that the CGEM? graft can be scaled-up in a reproducible, quality and sterile way will provide the necessary assurance safety and efficacy data to apply for a first in humans study with the FDA. The success of this Phase 2 SBIR project will result in the development of an ?off-the-shelf? human ligament graft ready for use in ACL repairs.
Approximately 350,000 anterior cruciate ligament (ACL) reconstruction surgeries are performed in the US each year, and billions of dollars are spent on the acute care costs involved in these procedures. The most common ACL replacement strategies involve autogenic or allogenic tendon grafts that never fully integrate with the bone tunnel created during surgery and knee joints that do not recover pre-injury level biomechanics. Our CGEM? (cell-generated matrix) graft is an innovative and paradigm-shifting approach to ligament replacement offers the possibility of a radical improvement in outcomes for patients who suffer acute knee injury including the complete restoration of native knee biomechanics and potential reductions in associated early onset of osteoarthritis.
