Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior.However,capturing these signals within hydrogel and directing over time has still been unr...Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior.However,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes.Here,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue remodeling.This bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors.Besides,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal pathway.Furthermore,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone.展开更多
基金This research was funded by The National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China General Program(81930051)+3 种基金Postdoctoral Research Foundation of China(2020M681319)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2019ZDA05 and ZH2018ZDA04)“The Project Supported by the Foundation of National Facility for Translational Medicine(Shanghai)(TMSK-2020-117)”Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906).
文摘Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior.However,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes.Here,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue remodeling.This bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors.Besides,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal pathway.Furthermore,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone.