Abstract
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 dual-crosslinked 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.