Mechanochemical Regulation of Muscle on Developing Cartilage

肌肉对软骨发育的机械化学调节

• 批准号: RGPIN-2019-04906
• 负责人: Rainbow, Roshni
• 金额: $ 2.04万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=759870
• 关键词: Mechanochemical; Regulation; Muscle; Developing; Cartilage

Introduction Tissue engineering aims to create new tissues for restoring the form and function of native structures lost to injury, aging, or disease. Morphogenesis defines the developmental processes by which native tissues take shape as they mature towards their functioning adult form. This program offers an exciting opportunity to study tissue formation by integrating morphogenic constituents with tissue engineering to establish a morphogenesis-driven platform for engineering functional tissues. Background/Rationale Native tissues develop through a coordinated interplay between mechanical and biochemical signals, with simultaneous contributions from neighbouring tissues. While animal models have been employed to identify many morphogenic processes, analysis tools often capture morphogenesis at discrete time points. By observing a continuous system as a snapshot, this spatial and temporal discretization describes tissue formation as an isolated event in time and space. To address this challenge, a modular co-culture bioreactor is proposed as a continuous platform for studying the mechanochemical interactions of neighbouring tissues. Objectives/Methodology My long-term program goal is to understand the role of neighbouring tissues during morphogenesis and establish strategies that integrate developmental mechanisms to engineer functional load-bearing tissues. Three objectives are proposed to identify the regulation of muscle on developing cartilage and to establish new cartilage tissue engineering strategies; this work will train 2 PhD, 1 MASc, and 5 undergraduate students. Objective 1 - Develop a modular bioreactor for co-culturing muscle and cartilage. This bioreactor will allow for the spatial co-culturing of muscle and cartilage, permitting the study of individual tissues under mechanical stimulation and for biochemical interactions between tissues. Objective 2 - Identify the mechanochemical regulation of muscle on developing cartilage. This work will use the modular bioreactor platform to identify the biochemical role of contracting muscle on developing engineered cartilage. Objective 3 - Establish cartilage tissue engineering strategies that integrate mechanochemical regulatory mechanisms from muscle. This work will incorporate muscle-derived mediators into strategies to engineer functional cartilage. Impact This interdisciplinary work aims to integrate morphogenic mechanisms into musculoskeletal tissue engineering, thereby providing a platform to design functional engineered tissue and promoting a diverse training environment for HQP. Future work can extend this approach to other load-bearing tissues and may contribute to the translational development of commercially-viable strategies for cartilage tissue engineering, MEMS sensors, and mechanochemically regulating biomaterials. By building collaborations with biomedical industries, technological advancements will have economic, environmental, and social benefit to Canadians.

简介 组织工程旨在创造新的组织，以恢复因损伤、衰老或疾病而丧失的天然结构的形式和功能。形态发生定义了天然组织在成熟到具有功能的成人形式时形成的发育过程。通过将形态发生成分与组织工程相结合来研究组织形成，以建立用于工程功能组织的形态发生驱动平台，这是一个令人兴奋的机会。 背景/基本原理 天然组织通过机械和生化信号之间的协调相互作用而发展，同时来自邻近组织的贡献。动物模型已被用来识别许多形态发生过程，分析工具通常通过将连续系统观察为快照来捕获形态发生，这种空间和时间离散将组织形成描述为时间和空间上的孤立事件。挑战，提出了一种模块化共培养生物反应器作为研究邻近组织的机械化学相互作用的连续平台。 目标/方法我的长期计划目标是了解邻近组织在形态发生过程中的作用并建立整合策略。提出了三个目标来确定肌肉对软骨发育的调节并建立新的软骨组织工程策略；这项工作将培养 2 名博士生、1 名硕士生和 5 名本科生。开发用于共培养肌肉和软骨的模块化生物反应器该生物反应器将允许肌肉和软骨的空间共培养，从而可以研究机械刺激下的单个组织以及之间的生化相互作用。目标 2 - 确定肌肉对软骨发育的机械化学调节作用。 这项工作将使用模块化生物反应器平台来确定收缩肌肉对工程软骨发育的生化作用。 目标 3 - 建立整合机械化学调节机制的软骨组织工程策略。这项工作将把肌肉衍生的介质纳入设计功能性软骨的策略中。影响这项跨学科的工作旨在将形态发生机制整合到肌肉骨骼组织工程中，从而提供一个平台。设计功能性工程组织并促进 HQP 多样化的培训环境，未来的工作可以将这种方法扩展到其他承重组织，并可能有助于软骨组织工程、MEMS 传感器和机械化学调节生物材料的商业可行策略的转化开发。通过与生物医学行业建立合作，技术进步将为加拿大人带来经济、环境和社会效益。