Mechanochemical Regulation of Muscle on Developing Cartilage

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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.