High‐Strength Gelatin Hydrogel Scaffold with Drug Loading Remodels the Inflammatory Microenvironment to Enhance Osteoporotic Bone Repair

Abstract

Abstract Osteoporosis is a widespread condition that induces an inflammatory microenvironment, limiting the effectiveness of conventional therapies and presenting significant challenges for bone defect repair. To address these issues, a high‐strength gelatin hydrogel scaffold loaded with roxadustat is developed, specifically designed to remodel the inflammatory microenvironment and enhance osteoporotic bone regeneration. By incorporating minimal methacrylated hyaluronic acid (HAMA) into an o ‐nitrobenzyl functionalized gelatin (GelNB) matrix, a gelatin hydrogel with a fracture strength of 10 MPa is achieved, providing exceptional structural stability and enabling precise scaffold fabrication through digital light processing (DLP) 3D printing. Validated through cell experiments and animal studies, the hydrogel scaffold supports cell adhesion and migration, offers excellent tissue compatibility, and is fully degradable, meeting the requirements of a therapeutic scaffold. Including roxadustat further enhances the scaffold's functionality by regulating the inflammatory microenvironment via hypoxia‐inducible factor‐1α (HIF‐1α) signaling, significantly improving bone defect repair in osteoporotic models. This drug‐loaded scaffold effectively addresses inflammation‐induced limitations and enhances the regenerative capacity of the affected area, paving the way for improved therapeutic outcomes in osteoporotic bone repair.