Carbon Dot-Linked Hydrogel-Composite Scaffold with Sequential Release of Multi-Drug for Bone Repair.

Bone repair is a complex and dynamic process that demands implanted scaffolds to provide temporal-specific functions: antibacterial activity in the early stage, followed by angiogenic and osteogenic stimulation in later stages. This study introduces a biomimetic scaffold composed of a filled Gel-OSA hydrogel and a 3D-printed PLA framework, enabling sequential multi-drug release for bone regeneration. Zero-dimensional arginine-derived carbon dots were incorporated into the hydrogel to achieve rapid release after implantation, conferring potent antibacterial activity and ROS regulation. Meanwhile, chondroitin sulfate (CS)-loaded mesoporous bioactive glass nanoparticles were immobilized onto the 3D-printed PLA surface via a polydopamine coating, allowing sustained release of CS and Ca/P ions to enhance the scaffold's long-term osteoinductive capability. The composite scaffold further demonstrated combined effects in promoting cell proliferation and osteogenic differentiation in vitro. Collectively, these findings suggest that this biomimetic scaffold, designed for temporally controlled multi-drug release, represents a promising therapeutic strategy for the reconstruction of bone tissue.