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稳定性，但研究表明，机械稳定性可以通过特定的化学和机械刺激来增强。为了加快发现最佳刺激方案，需要提供研究平台，以便能够快速、清晰和可靠地传达功能结果（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试样材料测试系统保留的准确性。因此，该系统能够映射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育。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试验室中提供准确机械刺激和材料性能评价的能力。将使用外部传感器量化载荷条件和样本几何形状对精确机械刺激的影响。软TE支架和硬软骨塞的粘弹性材料特性将在六室生物反应器和常规单级测试装置中表征。将对生物反应器和模型试验系统之间的结果进行统计学比较。如果生物反应器的验证成功，我们预计该产品将提供一个经济可靠的研究平台，促进TE技术转移。 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，以促进快速发现促进机械活性组织合成的机械条件。

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 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.