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。虽然目前TE软骨缺乏天然软骨的机械稳定性，但研究表明，通过特定的化学和机械刺激可以增强其机械稳定性。为了加速最佳刺激方案的发现，研究平台需要能够快速、清晰和可靠地交流功能结果（即材料特性）。为了实现这一目标，我们引入了一个六室生物反应器，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。因此，该系统能够绘制暴露于高度特异性机械刺激方案的六个个体标本的功能发展图。为了保持成本效益和便携性，生物反应器利用系统冗余来消除硬件。本研究的具体目的是测试生物反应器在所有六个测试室中提供准确机械刺激和材料性能评估的能力。载荷条件和试样几何形状对精确机械刺激的影响将使用外部传感器进行量化。软TE支架和硬软骨塞的粘弹性材料性能将在六室生物反应器和传统的单级测试装置中进行表征。生物反应器与模型测试系统的结果将进行统计比较。如果生物反应器的验证成功，我们设想该产品将提供一个经济可靠的研究平台，促进TE技术的转移。

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 develop replacement cartilage using tissue engineering (TE) technologies. Although TE cartilage presently lacks the mechanical stability of native cartilage, studies have demonstrated that mechanical stability can be enhanced with specific chemical and mechanical stimuli. 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 material properties). Towards this goal, we introduce a six-chamber bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. This system is therefore capable of mapping functional development of six individual specimens exposed to highly-specific mechanical stimulation protocols. To remain cost-effective and portable, the bioreactor leverages system redundancies to eliminate hardware. The specific aim of this study is to test the bioreactor's capacity to deliver accurate mechanical stimulations and material property evaluations in all six test chambers. The effect of loading conditions and specimen geometry on accurate mechanical stimulation will be quantified using external sensors. The viscoelastic material properties of soft TE scaffolds and stiff cartilage plugs will be characterized in both the six-chamber bioreactor and a conventional single-stage testing device. Results between the bioreactor and the model testing system will be statistically compared. If validation of the bioreactor is successful, we envision this product will provide an economical and reliable research platform that fosters TE technology transfer. 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 synthesis of mechanically viable tissue.