Mechanochemical Regulation of Muscle on Developing Cartilage

组织工程旨在创造新的组织，以恢复因损伤、衰老或疾病而失去的原有结构的形式和功能。形态发生（Morphogenesis）定义了原生组织在成熟到具有功能的成体时形成的发育过程。该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，从而建立一个形态发生驱动的工程功能组织平台。******背景/原理原生组织通过机械和生化信号之间的协调相互作用而发展，并同时得到邻近组织的贡献。虽然动物模型已被用于识别许多形态发生过程，但分析工具通常在离散时间点捕获形态发生。通过观察连续系统作为快照，这种空间和时间离散化将组织形成描述为时间和空间中的孤立事件。为了解决这一挑战，提出了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/方法我的长期项目目标是了解邻近组织在形态发生过程中的作用，并建立整合发育机制的策略来设计功能承重组织。提出了三个目标，以确定肌肉对软骨发育的调节和建立新的软骨组织工程策略；培养博士2名，硕士1名，本科生5名。******目的1：开发一种用于肌肉和软骨共培养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，允许在机械刺激下研究单个组织和组织之间的生化相互作用。******目的2确定肌肉对软骨发育的机械化学调控。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开发工程软骨中的生化作用。******目的3建立软骨组织工程策略，整合肌肉的机械化学调节机制。这项工作将把肌肉来源的介质纳入工程功能软骨的策略。******影响本跨学科工作旨在将形态发生机制整合到肌肉骨骼组织工程中，从而为设计功能性工程组织提供平台，促进HQP多样化的训练环境。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.