The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic th...The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic the growth plate's structure,supporting regeneration and bone growth.Composed of aldehyde-modified bacterial cellulose(DBNC),methacrylated gelatin(GelMA)and sodium alginate(Alg),the hydrogel is engineered through ionic bonding and Schiff base reactions,creating a macroporous structure.This structure can transform into a denser form by binding with calcium ions.In vitro,the loose macroporous structure of the hydrogels can promote chondrogenic differentiation,and when it forms a dense structure by binding with calcium ions,it also can activate relevant chondrogenic signaling pathways under the influence of insulin-like growth factor I(IGF-1),further inhibiting osteogenesis.In vivo experiments in a rat model of growth plate injury demonstrated that the hydrogel promoted growth plate cartilage regeneration and minimized bone bridge formation by creating a hypoxic microenvironment that activates IGF-1-related pathways.This environment encourages chondrogenic differentiation while preventing the undesired formation of bone tissue within the growth plate area.Overall,the dual-crosslinked hydrogel not only mimics the growth plate's structure but also facilitates localized IGF-1 expression,effectively reshaping the growth plate's function.This approach represents a promising therapeutic strategy for treating growth plate injuries,potentially addressing challenges associated with skeletal growth restoration in pediatric patients.展开更多
基金sponsored by the National Natural Science Foundation of China(U23A20406/32301095)Shanghai Science and Technology Program(22YF1441700)Shanghai Municipal Health Commission(20244Y0178).
文摘The growth plate is crucial for skeletal growth in children,but research on repairing growth plate damage and restoring growth is limited.Here,a high-toughness adaptive dualcrosslinked hydrogel is designed to mimic the growth plate's structure,supporting regeneration and bone growth.Composed of aldehyde-modified bacterial cellulose(DBNC),methacrylated gelatin(GelMA)and sodium alginate(Alg),the hydrogel is engineered through ionic bonding and Schiff base reactions,creating a macroporous structure.This structure can transform into a denser form by binding with calcium ions.In vitro,the loose macroporous structure of the hydrogels can promote chondrogenic differentiation,and when it forms a dense structure by binding with calcium ions,it also can activate relevant chondrogenic signaling pathways under the influence of insulin-like growth factor I(IGF-1),further inhibiting osteogenesis.In vivo experiments in a rat model of growth plate injury demonstrated that the hydrogel promoted growth plate cartilage regeneration and minimized bone bridge formation by creating a hypoxic microenvironment that activates IGF-1-related pathways.This environment encourages chondrogenic differentiation while preventing the undesired formation of bone tissue within the growth plate area.Overall,the dual-crosslinked hydrogel not only mimics the growth plate's structure but also facilitates localized IGF-1 expression,effectively reshaping the growth plate's function.This approach represents a promising therapeutic strategy for treating growth plate injuries,potentially addressing challenges associated with skeletal growth restoration in pediatric patients.
