Enabling regeneration by mechano-therapeutics – novel strategies for musculoskeletal healing

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Prof. Georg N. Duda




Both scar formation and restitution ad integrum during bone regeneration rely on processes of cellular assembly that involve cell contraction, cell-matrix interactions, and matrix formation. Scar-free healing requires a balanced downregulation of inflammation. Especially in musculoskeletal healing, mechanical re-formation and immunological re-balance appear coupled, but so far this coupling is little understood. The local immune-reaction in bone healing and the mechanical, tissue-based re-establishment of matrix integrity and pre-tension are characterized by a tight coupling – Immuno-Mechanics. To regain tissue integrity, healing starts with bleeding and hematoma formation. At this stage, pro-inflammatory cells, as well as fibroblasts, invade the wound site to initiate the healing process. However, the wound set also represents a mechanically challenging and unstable environment, with instability and shear at interfaces and liquid flow in and out of the wound site. Successful healing requires immune cells to steer local inflammation and mechanical forces to drive tissue re-organization. We propose that scar formation occurs when tissue contraction exceeds a critical threshold and/or is coupled to a disbalanced local adaptive immunity. Understanding the details and mechanisms of this immuno-mechanical linkage is crucial for reducing scar formation and empowering restored tissue integrity. We could show that mechano-therapeutic strategies allow to modulate and alter this immuno-mechanical coupling and empower scarfree or scar-less healing.