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

这项小企业技术转移（STTR）第一阶段项目的更广泛影响和商业潜力是将一种用于前交叉韧带（ACL）置换的新型组织工程移植物推向市场。前交叉韧带撕裂是运动员中最常见的膝关节损伤之一。现有的修复选择使用从患者体内采集的组织，导致供体部位发病率和术后疼痛，或从尸体上采集的组织，与疾病传播和再撕裂的风险增加有关。此外，目前的两种移植物都被设计得很坚硬，超过了原有的前交叉韧带特性，从而保护再生组织免受最佳组织生长所需的机械信号的影响。不能再生正常的前交叉韧带功能会导致恢复到竞技水平的减少，并导致早发性骨关节炎的风险增加。利用可扩展的组织工程移植物能够响应局部负荷环境，应恢复ACL的正常功能，并改善患者的长期预后。这项新技术的应用将为韧带修复和其他软组织损伤部位定义新的治疗策略，并提高我们对体内组织再生的理解。拟议的项目解决了组织工程产品从实验室到临床的商业化和转化所固有的重大制造和生物处理挑战。除了证明临床疗效和符合监管标准外，新的组织工程产品还需要具有成本效益的制造工艺，并提供更高的成本效益比，以取代现有的移植物选择。该项目将首先开发一种新型的、自动化的、封闭的生物反应器系统，该系统将为生产和储存经fda批准的标准化临床工程组织提供方便。其次，将多个生物反应器集成在一起，同时经济高效地制造多种组织结构，用于生理、制药和医疗应用，填补了该领域的重要知识空白。在早期研究阶段实施自动化制造系统有可能显著减少组织工程技术和公司在未来上市前阶段可能遇到的技术、监管和商业障碍。此外，生物反应器可以作为其他组织工程技术的模型或平台，试图将其实验室流程简化为能够满足临床需求的安全、可重复、适当规模的制造流程。

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.