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

该小企业技术转让（STTR）I期项目的更广泛影响/商业潜力是将用于前交叉韧带（ACL）置换的新型组织工程移植物推向市场。ACL撕裂是运动员中最常见的膝关节损伤之一。现有的修复选择利用从患者身体采集的组织，导致供体部位发病和术后疼痛，或者利用从尸体采集的组织，这与疾病传播和再撕裂的风险增加有关。此外，目前的两种移植物选择都设计为刚性的，并且超过了原生ACL的性能，从而使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ACL功能导致恢复到竞争水平的活动减少，并导致早发性骨关节炎的风险增加。利用能够响应局部负荷环境的可伸展组织工程移植物应使ACL恢复正常功能并改善患者的长期结局。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翻译所固有的重大制造和生物加工挑战。除了证明临床疗效和满足监管标准外，新的组织工程产品还需要具有成本效益的制造工艺，并提供改善的成本效益比，以取代现有的移植物选择。该项目将首先开发一种新型、自动化和封闭的生物反应器系统，该系统将提供轻松制造和储存标准化FDA批准的工程组织临床使用的方法。其次，将集成多个生物反应器，以同时且具有成本效益地制造用于生理学、药学和医学应用的多个组织结构，从而填补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大大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，试图将其实验室过程简化为能够满足临床需求的安全、可重现、适当规模的制造过程。

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.