Immuno-osteoinductive 3D printed hydrogel scaffolds with triple crosslinking and GA/EGCG release for bone healing.

Bone defects, caused by trauma, osteomyelitis, or osteoporosis, represent a significant global health challenge in orthopedics. However, current bone repair strategies often neglect the critical role of the immune microenvironment, which can impede effective bone regeneration. To address this gap, we developed a 3D-printed triple crosslinked hydrogel scaffold incorporating slow-release glycopyrrolate (GA) and epigallocatechin gallate (EGCG), that it could promote bone regeneration by modulating the immune response. We evaluated their immunomodulatory and bone-regenerative effects through in vitro cellular experiments and rat cranial defect models. Results demonstrated that these scaffolds effectively modulated the immune microenvironment, reducing inflammation while promoting osteoblast differentiation and proliferation, thereby significantly enhancing new bone formation and density. In conclusion, our novel 3D-printed hydrogel scaffold offers a promising approach to bone defect repair through its unique combination of mechanical strength, immunomodulation, and osteogenesis. This study provides valuable insights into leveraging immunomodulatory agents for enhanced bone regeneration, highlighting potential clinical applications.