Uninterrupted dynamic stiffening microenvironment enhances the paracrine function of mesenchymal stem cells for vascularization through chromatin remodeling

Abstract

The stiffness of extracellular matrix is dynamically stiffened during bone formation. Paracrine of angiogenic factors in mesenchymal stem cells (MSCs) plays an essential role during tissue regeneration. Whether the paracrine of angiogenic factors in MSCs is influenced by the mechanical microenvironment of materials, especially dynamic matrix mechanics of materials largely remains unknown. A matrix dynamic stiffening material previous designed was used here to explore whether matrix dynamic stiffening could influence paracrine of angiogenic factors in MSCs. The cytoskeleton polymerization, chromatin remodeling and histone acetylation in MSCs were analyzed using phalloidin staining, chromatin condensation parameter analysis and immunofluorescent staining. The results found that the paracrine of MSCs cultured on dynamic stiffening material was higher than that on static stiffness materials. The cytoskeletal polymerization and nuclear deformation degrees of MSCs seeded on dynamic stiffening material were significantly higher than those seeded on materials with static stiffness. The dynamic stiffening substrate could promote the cytoskeletal polymerization to increase the nuclear deformation of MSCs and further induce the paracrine of MSCs. These findings will help to provide clinical guidelines for designing vascularized bone repair materials with appropriate mechanical properties.