3D-Printable GelMA/PEGDA Hydrogel Promotes Bone Regeneration through SIRT1-Mediated Angiogenesis and Osteogenesis

The integration of angiogenesis and osteogenesis is critical for effective bone regeneration, necessitating the development of multifunctional biomaterials. This study presents a 3D-printable GelMA/PEGDA hydrogel loaded with resveratrol (Res), designed to promote bone regeneration through SIRT1-mediated angiogenesis and osteogenesis. The hydrogel exhibits excellent printability and biocompatibility, providing a supportive matrix for cell growth and differentiation. Resveratrol, a potent activator of SIRT1, is incorporated to enhance angiogenic and osteogenic pathways. In vitro studies demonstrate that the GelMA/PEGDA@Res hydrogel significantly upregulates the expression of angiogenic factors, leading to improved vascularization. In vivo, the hydrogel accelerates bone healing in a rat calvarial defect model, evidenced by enhanced blood vessel formation and bone tissue regeneration. These findings suggest that the GelMA/PEGDA-resveratrol hydrogel is a promising candidate for bone tissue engineering, offering a dual-function approach to drive both angiogenesis and osteogenesis through SIRT1 activation. This work provides a novel strategy for the development of bioactive scaffolds that integrate drug delivery with tissue engineering for regenerative medicine. • The 3D-printed GelMA/PEGDA@Res hydrogel promotes bone regeneration via SIRT1 signaling. • The hydrogel exhibits a porous architecture and sustained resveratrol release. • In vitro, it upregulates angiogenic factors and enhances vascularization. • In vivo, the hydrogel accelerates bone healing and blood vessel formation.