Cartilage Mechnobiology

关节软骨是一种致密的结缔组织，几乎完全为滑膜关节提供机械作用。由于天然软骨具有较强的自我修复能力，因此人们一直致力于关节表面工程化软骨的开发。然而，由于工程化组织通常不如天然软骨，提高组织性能的一种策略是在组织生长过程中应用机械载荷。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相当有限。造成这种有限的细胞反应的主要因素是：(I)只有一小部分细胞似乎对刺激有直接反应；(Ii)软骨细胞在长期负荷下往往迅速脱敏。我的NSERC资助研究项目的长期目标是提高软骨细胞对机械负荷的响应性，最终导致更好的工程化软骨的发展。为了实现这一目标，本研究计划的短期目标是：(I)研究软骨细胞对机械负荷的异质性反应的机制；(Ii)调查负荷诱导软骨细胞脱敏的机制；以及(Iii)开发新的刺激方法来提高细胞的敏感性。 这项研究有望对生物力学工程学科做出重大贡献，加深我们对软骨细胞对尚未研究的机械载荷区域的异种和脱敏反应的认识。提高细胞对机械刺激的敏感性的能力对于开发新的机械生物学研究方法和设备具有直接的工业应用。同样，需要改进的方法来创造适合软骨修复和重建的功能性、承重组织。在接下来的五年里，这项研究计划还将为生物医学工程的专业生涯培养9名HQP(2名博士，3名硕士和4名本科生)。在这些项目中工作的HQP将有机会参与跨学科研究，并获得细胞机械生物学和组织工程领域的基本知识和实践经验。

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. The proposed research is expected to make significant contributions to the discipline of Biomechanical Engineering by furthering our knowledge of the heterogenic and desensitization responses of cartilage cells to mechanical loading areas which have not yet been studied. The ability to improve cellular sensitivity to mechanical stimuli has direct industrial applications towards the development new methods and devices for mechanobiology research. Similarly, improved methodologies are needed to create functional, load-bearing tissues suitable for cartilage repair and reconstruction. Over the next five years, this research program will also prepare 9 HQP (2 PhD, 3 MASc, and 4 undergraduates) for professional careers in biomedical engineering. HQP working on these projects will have the opportunity to be involved in interdisciplinary research and to acquire fundamental knowledge and practical experience in the areas of cellular mechanobiology and tissue engineering.