The dynamic extracellular matrix(ECM)constantly affects the behaviors of cells.To mimic the dynamics of ECM with controllable stiffness and energy dissipation,this study proposes a strategy in which a small molecule,3...The dynamic extracellular matrix(ECM)constantly affects the behaviors of cells.To mimic the dynamics of ECM with controllable stiffness and energy dissipation,this study proposes a strategy in which a small molecule,3,4-dihydroxybenzaldehyde(DB),was used as fast"dynamic bridges"to construct viscoelastic gelatin methacryloyl(GelMA)-based hydrogels.The storage modulus and loss modulus of hydrogels were independently adjusted by the covalent crosslinking density and by the number of dynamic bonds.The hydrogels exhibited self-healing property,injectability,excellent adhesion and mechanical properties.Moreover,the in vitro results revealed that the viscous dissipation of hydrogels favored the spreading,proliferation,osteogenesis and chondrogenesis of bone marrow mesenchymal stem cells(BMSCs),but suppressed their adipogenesis.RNA-sequencing and immunofluorescence suggested that the viscous dissipation of hydrogels activated Yes-associated protein(YAP)by stabilizing integrinβ1,and further promoted nuclear translocation of smad2/3 andβ-catenin to enhance chondrogenesis and osteogenesis.As a result,the viscoelastic GelMA hydrogels with highest loss modulus showed best effect in cartilage and subchondral bone repair.Taken together,findings from this study reveal an effective strategy to fabricate viscoelastic hydrogels for modulating the interactions between cells and dynamic ECM to promote tissue regeneration.展开更多
基金This work was supported by National Natural Science Foundation of China(81871805,81925027 and 32130059)Jiangsu Provincial Clinical Orthopedic Center,Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology,the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘The dynamic extracellular matrix(ECM)constantly affects the behaviors of cells.To mimic the dynamics of ECM with controllable stiffness and energy dissipation,this study proposes a strategy in which a small molecule,3,4-dihydroxybenzaldehyde(DB),was used as fast"dynamic bridges"to construct viscoelastic gelatin methacryloyl(GelMA)-based hydrogels.The storage modulus and loss modulus of hydrogels were independently adjusted by the covalent crosslinking density and by the number of dynamic bonds.The hydrogels exhibited self-healing property,injectability,excellent adhesion and mechanical properties.Moreover,the in vitro results revealed that the viscous dissipation of hydrogels favored the spreading,proliferation,osteogenesis and chondrogenesis of bone marrow mesenchymal stem cells(BMSCs),but suppressed their adipogenesis.RNA-sequencing and immunofluorescence suggested that the viscous dissipation of hydrogels activated Yes-associated protein(YAP)by stabilizing integrinβ1,and further promoted nuclear translocation of smad2/3 andβ-catenin to enhance chondrogenesis and osteogenesis.As a result,the viscoelastic GelMA hydrogels with highest loss modulus showed best effect in cartilage and subchondral bone repair.Taken together,findings from this study reveal an effective strategy to fabricate viscoelastic hydrogels for modulating the interactions between cells and dynamic ECM to promote tissue regeneration.
