Cartilage Mechnobiology

软骨力学生物学

• 批准号: RGPIN-2016-04124
• 负责人: Waldman, Stephen
• 金额: $ 2.11万
• 依托单位: Ryerson University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=667966
• 关键词: Cartilage; Mechnobiology

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.**

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）开发新的刺激方法来提高细胞的敏感性。拟议的研究预计将通过进一步了解软骨细胞对机械负荷的异质性和脱敏反应-尚未研究的领域，为生物力学工程学科做出重大贡献。提高细胞对机械刺激的敏感性的能力直接应用于机械生物学研究的新方法和设备的开发。类似地，需要改进的方法来产生适合于软骨修复和重建的功能性承重组织。在接下来的五年里，该研究计划还将为生物医学工程的职业生涯准备9名HQP（2名博士，3名硕士和4名本科生）。从事这些项目的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础知识和实践经验。