A Cost-effective Bioreactor to Advance Functional Tissue Engineering of Cartilage

描述（由申请人提供）：骨关节炎（OA）是美国慢性残疾的主要原因。治疗和预防骨关节炎的临床目标是利用组织工程（TE）技术开发替代软骨。尽管TE软骨目前缺乏天然软骨的机械弹性，但通过在培养过程中施加化学和机械刺激，TE构建物的机械性能可以得到增强。为了加快最佳增产方案的发现，需要有研究平台来实现功能结果（即机械性能）的快速、清晰和可靠的交流。为了实现这一目标，我们推出了一个紧凑的六站生物反应器，它结合了批量测试的效率和通常为专用单样品材料测试系统保留的准确性。在非常成功的第一阶段可行性研究中，一种创新的方法被证明可以提供准确的动态刺激并评估六个站点的机械性能。这项技术现在可以整合到一个多轴框架，使用混合和自适应控制，以最大限度地提高测试效率和灵活性。这个应用程序的前三个目标是：1)提高吞吐量，2)添加加载模式，3)自动化性能和分析工具。这些修改对机械精度的影响将使用外部传感器和成像方法进行验证。水凝胶和牛软骨将在高通量生物反应器和传统的单站测试系统中进行测试，以验证生物反应器机械性能的自动测量。系统稳健性将通过量化操作生物反应器数百万次循环的效果来确定。在

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of chronic disability in the United States. A clinical goal in the treatment and prevention of OA is to develo replacement cartilage using tissue engineering (TE) technologies. Although TE cartilage currently lacks the mechanical resilience of native cartilage, the mechanical properties of TE constructs can be enhanced by applying chemical and mechanical stimuli during culture. To speed the discovery of optimal stimulation protocols, research platforms need to be available that enable fast, clear and reliable communication of functional outcomes (i.e. mechanical properties). Towards this goal, we introduce a compact six-station bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. In the highly successful phase I feasibility study, an innovative method was proven to deliver accurate dynamic stimulations and evaluate mechanical properties in six stations. This technology can now be incorporated into a multi-axial frame that uses hybrid and adaptive controls to maximize testing efficiency and flexibility. The first three aims of this application are to 1) increase throughput, 2) add loading modalities and 3) automate performance and analysis tools. The effect of these modifications on mechanical accuracy will be verified using external sensors and imaging methods. Hydrogels and bovine cartilage will be tested in the high- throughput bioreactor and a conventional single-station test system to validate the bioreactors automated measurement of mechanical properties. System robustness will be determined by quantifying the effect of operating the bioreactor for millions of cycles. In the fourth aim, bioreactor prototypes will be distributed to three cartilage TE laboratories to evaluate and optimize the bioreactor prior to commercial launch. Successful completion of the study aims will provide an efficient, reliable and flexible research platform to advance the development and clinical transfer of cartilage TE technology. PUBLIC HEALTH RELEVANCE: Tissue engineering of articular cartilage presents a promising strategy for treatment of osteoarthritis, a debilitating and prevalent disease. Cartilage engineering techniques, however, are currently unable to reproduce the mechanical properties critical to native cartilage, thus impeding the transfer of TE technology to patient care. A bioreactor is therefore proposed to facilitate the rapid discovery of mechanical conditions that promote the biosynthesis of mechanically viable tissue.