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。治疗和预防骨性关节炎的一个临床目标是利用组织工程(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，但在培养过程中通过施加化学和机械刺激可以提高TE结构的力学性能。为了加快最佳刺激方案的发现，需要有研究平台，使功能结果(即机械特性)能够快速、清晰和可靠地交流。为了实现这一目标，我们引入了一种紧凑型六工位生物反应器，它结合了批量测试的效率和通常为专用单一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能够提供准确的动态刺激并评估六个站点的机械性能。这项技术现在可以被整合到使用混合和自适应控制的多轴框架中，以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)增加加载方式，3)自动化性能和分析工具。这些改进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常规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。系统的稳健性将通过量化生物反应器运行数百万个周期的影响来确定。在……里面 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，以在商业推出之前对生物反应器进行评估和优化。研究目标的成功完成将为推进软骨TE技术的开发和临床转移提供一个高效、可靠和灵活的研究平台。 公共卫生相关性：关节软骨的组织工程学为治疗骨关节炎提供了一种很有前途的策略，骨关节炎是一种令人衰弱的流行疾病。然而，软骨工程技术目前无法复制对天然软骨至关重要的力学性能，因此阻碍了TE技术向患者护理的转移。因此，提出了一种生物反应器，以促进促进机械可存活组织的生物合成的机械条件的快速发现。

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.