Cartilage Mechnobiology

关节软骨是一种致密的结缔组织，几乎专门在滑膜关节中提供机械作用。由于天然软骨的自我修复能力相对较弱，因此人们一直致力于开发用于关节表面置换的工程化软骨。然而，由于工程化组织通常劣于天然软骨，因此增强组织性质的一种策略是通过在组织生长期间施加机械载荷。虽然被广泛采用，但软骨细胞（软骨细胞）对机械刺激的实际反应非常有限。导致这种有限的细胞反应的主要因素是：（i）只有一部分细胞似乎直接对刺激作出反应;和（ii）软骨细胞在长期负荷下往往迅速脱敏。我的NSERC资助的研究计划的长期目标是提高软骨细胞对机械负荷的反应性，最终导致上级工程软骨的发展。为了实现这一目标，本研究计划的短期目标是：（i）调查负责软骨细胞对机械负荷的异质性反应的机制;（ii）调查负责负荷诱导的软骨细胞脱敏的机制;和（iii）开发新的刺激方法，以提高细胞的敏感性。

Articular cartilage is a dense connective tissue that almost exclusively provides a mechanical role in synovial joints. Due to native cartilage’s relative inability for self-repair, substantial efforts have been placed on the development of engineered cartilage for joint resurfacing. However, as the engineered tissues are typically inferior to native cartilage, one strategy to enhance tissue properties is through the application of mechanical loading during tissue growth. Although widely adopted, the actual response of cartilage cells (chondrocytes) to mechanical stimuli is quite limited. The major factors that contribute to this limited cellular response are: (i) only a fraction of the cells appear to directly respond to the stimulus; and (ii) chondrocytes tend to rapidly desensitize under prolonged loading. The long-term goal of my NSERC funded research program is to improve the responsiveness of chondrocytes to mechanical loading, ultimately leading to the development of superior engineered cartilage. To achieve this goal, the short-term objectives of this research program are to: (i) investigate the mechanisms responsible for the heterogenic response of chondrocytes to mechanical loading; (ii) investigate the mechanisms responsible for load-induced chondrocyte desensitization; and (iii) develop new stimulation methods to improve cellular sensitivity.