STTR Phase I: Development of an Automated Bioreactor System for Tissue Engineered Anterior Cruciate Ligament (ACL) Graft Production.

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to bring to market a novel tissue engineered graft for anterior cruciate ligament (ACL) replacement. Tears of the ACL are one of the most common knee injures among athletes. Existing repair options utilize tissue harvested from the patient's body resulting in donor site morbidity and post-operative pain or tissues harvested from cadavers, associated with increased risks of disease transmission and re-tearing. Additionally, both current graft options are designed to be stiff and exceed the native ACL properties, shielding the regenerating tissue from mechanical signals necessary for optimal tissue growth. Failure to regenerate normal ACL function leads to diminished return to competitive levels of activity and leads to increased risk of early onset osteoarthritis. Utilization of an extensible tissue engineered graft capable of responding to local loading environment should return normal function to the ACL and improve long-term patient outcomes. The application of this novel technology will define new treatment strategies for ligament repair and other sites of soft tissue injury and improve our understanding of tissue regeneration within the body. The proposed project addresses significant manufacturing and bioprocessing challenges inherent to the commercialization and translation of tissue engineered products from the laboratory to the clinic. In addition to demonstrating clinical efficacy and meeting regulatory standards, a new tissue engineered product needs to have a cost-effective manufacturing processes and deliver an improved cost-benefit ratio to displace existing graft options. This project will first develop a novel, automated, and closed bioreactor system that will provide the means to easily manufacture and store standardized FDA-approved engineered tissues clinical use. Second, multiple bioreactors will be integrated to simultaneously and cost-effectively fabricate multiple tissue constructs for physiological, pharmaceutical, and medical applications, fulfilling an important knowledge gap in the field. The implementation of an automated manufacturing system during the early research stage has the potential to significantly lessen the technical, regulatory, and commercial barriers that tissue-engineering technologies and companies are likely to encounter in the future pre-market stages. In addition, the bioreactor may serve as a model or platform for other tissue-engineering technologies attempting to streamline their laboratory processes into safe, reproducible, appropriately scaled manufacturing processes capable to meeting clinical demand.