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OA的临床目标是使用组织工程（TE）技术开发替代软骨。虽然TE软骨目前缺乏天然软骨的机械弹性，但TE构建体的机械性能可以通过在培养期间施加化学和机械刺激来增强。为了加快最佳刺激方案的发现，需要提供研究平台，以实现功能结果（即机械性能）的快速，清晰和可靠的通信。为了实现这一目标，我们引入了一种紧凑的六工位生物反应器，它结合了批量测试的效率和通常为专用单试样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模拟并评估六个站点的机械性能。该技术现在可以集成到多轴框架中，该框架使用混合和自适应控制来最大限度地提高测试效率和灵活性。该应用程序的前三个目标是：1）增加吞吐量，2）添加加载模式，3）自动化性能和分析工具。将使用外部传感器和成像方法验证这些修改对机械精度的影响。将在高通量生物反应器和常规单站测试系统中测试水凝胶和牛软骨，以验证生物反应器机械特性的自动测量。将通过量化操作生物反应器数百万次循环的影响来确定系统耐用性。在 第四个目标是，生物反应器原型将被分发到三个软骨TE实验室，以在商业发布之前评估和优化生物反应器。研究目标的成功完成将提供一个高效、可靠和灵活的研究平台，以推进软骨TE技术的开发和临床转移。 公共卫生相关性：关节软骨组织工程为骨关节炎的治疗提供了一个很有前途的策略。然而，软骨工程技术目前无法重现对天然软骨至关重要的机械性能，从而阻碍了TE技术向患者护理的转移。因此，提出了一种生物反应器，以便于快速发现促进机械活性组织生物合成的机械条件。

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.