Up IGF-I via high-toughness adaptive hydrogels for remodeling growth plate of children.

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.