Mechanochemical Regulation of Muscle on Developing Cartilage

组织工程学导论旨在创造新的组织，以恢复因损伤、老化或疾病而丧失的自然结构的形式和功能。形态发生定义了天然组织在成熟时形成其功能成体的发育过程。这一计划提供了一个令人兴奋的机会，通过将形态发生成分与组织工程相结合来研究组织形成，以建立一个形态发生驱动的功能组织工程平台。背景/原理：自然组织通过机械信号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。虽然动物模型已经被用来识别许多形态发生过程，但分析工具往往捕捉到离散时间点的形态发生。通过观察一个连续的系统作为快照，这种时空离散化将组织的形成描述为时间和空间上的孤立事件。为了应对这一挑战，提出了一种模块化的共培养生物反应器，作为研究邻近组织的机械力化学相互作用的连续平台。目的/方法论：我的长期计划目标是了解邻近组织在形态形成中的作用，并建立整合发育机制的策略来设计功能性承载组织。提出三个目标：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、1名硕士和5名本科生。目的1-研制一种用于肌肉和软骨共培养的模块化生物反应器。这种生物反应器将允许肌肉和软骨的空间共培养，允许在机械刺激下研究单个组织，并允许组织之间的生化相互作用。目的2-明确肌肉对软骨发育的机械力化学调节作用。这项工作将使用模块化生物反应器平台来确定收缩肌肉在形成工程化软骨方面的生化作用。目的3-建立整合肌肉机械力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体纳入到设计功能性软骨的策略中。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，从而提供一个设计功能工程组织的平台，并促进HQP的多样化培训环境。未来的工作可以将这种方法扩展到其他承载组织，并可能有助于翻译开发具有商业可行性的软骨组织工程、MEMS传感器和机械力化学调节生物材料的策略。通过与生物医药行业建立合作，技术进步将为加拿大人带来经济、环境和社会效益。

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.