Biological tissues,such as muscles and skin,exhibit remarkable on-demand modulation of their mechanical properties,allowing them to adapt to complex environmental conditions.For example,sea cucumber can rapidly stiffe...Biological tissues,such as muscles and skin,exhibit remarkable on-demand modulation of their mechanical properties,allowing them to adapt to complex environmental conditions.For example,sea cucumber can rapidly stiffen its skin for self-protection by regulating physical interactions among collagen fibrils[1].In stark contrast,conventional polymer materials,often relying on chemically cross-linked networks like vulcanized rubber,typically offer high mechanical strength but lack this crucial modulus adaptability due to the inert nature of covalent bonds.展开更多
Current strategies for cartilage repair,including decellularized cartilage matrices and synthetic bioactive materials,often encounter challenges such as immune responses and donor morbidity.In this study,we optimized ...Current strategies for cartilage repair,including decellularized cartilage matrices and synthetic bioactive materials,often encounter challenges such as immune responses and donor morbidity.In this study,we optimized an extracellular matrix(ECM)derived from mesenchymal stem cells through preconditioning with disease-associated inflammatory factors,specifically interleukin 6,tumor necrosis factor alpha,and interferon gamma(IFN-γ).Our in vitro experiments demonstrated that the cytokine-preconditioned stem-cell-derived ECM,especially IFN-γ-ECM,supports chondrocyte homeostasis by restoring mitochondrial energy metabolism.Furthermore,bioactive molecules secreted from this preconditioned ECM boost the recruitment of endogenous stem cells and facilitate their differentiation into chondrocytes.Notably,we found that IFN-γ-ECM facilitates the chondrogenic differentiation of mesenchymal stem cells through the activation of the integrin/phosphatidylinositol 3-kinase/Akt pathway and the Smad2/3 signaling cascade.These results highlight the potential of the cytokine-stimulated ECM,especially IFN-γ-ECM,to restore chondrocyte homeostasis,optimize the mobilization of endogenous stem cells,and substantially improve the regeneration of cartilage defects,offering a promising strategy for acellular cartilage graft reconstruction.展开更多
基金financially supported by the National Natural Science Foundation of China(52322306,22275032,and 52433003)the Shanghai Oriental Talent Program,the Shanghai Talent Development Fund(2021021)the Natural Science Foundation of Shanghai Basic Research Funding(25ZR1401006)。
文摘Biological tissues,such as muscles and skin,exhibit remarkable on-demand modulation of their mechanical properties,allowing them to adapt to complex environmental conditions.For example,sea cucumber can rapidly stiffen its skin for self-protection by regulating physical interactions among collagen fibrils[1].In stark contrast,conventional polymer materials,often relying on chemically cross-linked networks like vulcanized rubber,typically offer high mechanical strength but lack this crucial modulus adaptability due to the inert nature of covalent bonds.
基金supported by Chongqing medical scientific research project(Joint project of Chongqing Health Commission and Science and Technology Bureau)(2025MSXM019)the National Natural Science Foundation of China Joint Fund Project(82302755 and U22A20284)+5 种基金The Qian De Outstanding Young Talent Program of The First Affiliated Hospital of Chongqing Medical University(2025QDYQ-09)the Chongqing Medical Youth Top-notch Talent Program(YXQN202490)the First Clinical College Class-A Discipline Construction Project(472020320240008 and CYYY-BSYJSKYCXXM202423)the China Postdoctoral Science Foundation(2024M753873)the Hong Kong Scholars Program(XJ2024017)the Natural Science Foundation of Chongqing,China(CSTB2024NSCQ-MSX1200).
文摘Current strategies for cartilage repair,including decellularized cartilage matrices and synthetic bioactive materials,often encounter challenges such as immune responses and donor morbidity.In this study,we optimized an extracellular matrix(ECM)derived from mesenchymal stem cells through preconditioning with disease-associated inflammatory factors,specifically interleukin 6,tumor necrosis factor alpha,and interferon gamma(IFN-γ).Our in vitro experiments demonstrated that the cytokine-preconditioned stem-cell-derived ECM,especially IFN-γ-ECM,supports chondrocyte homeostasis by restoring mitochondrial energy metabolism.Furthermore,bioactive molecules secreted from this preconditioned ECM boost the recruitment of endogenous stem cells and facilitate their differentiation into chondrocytes.Notably,we found that IFN-γ-ECM facilitates the chondrogenic differentiation of mesenchymal stem cells through the activation of the integrin/phosphatidylinositol 3-kinase/Akt pathway and the Smad2/3 signaling cascade.These results highlight the potential of the cytokine-stimulated ECM,especially IFN-γ-ECM,to restore chondrocyte homeostasis,optimize the mobilization of endogenous stem cells,and substantially improve the regeneration of cartilage defects,offering a promising strategy for acellular cartilage graft reconstruction.
