Bioinspired honeycomb-mimetic adaptive hyaluronic acid hydrogel composite scaffold: intelligent prevention and treatment of infection of bone implants and promotion of bone repair

Addressing two major challenges in the field of bone implants: bacterial infection and delayed bone fusion, this study draws inspiration from the beehive structure to develop an adaptive enzyme-responsive hydrogel composite scaffold. The scaffold composed of an intermittently 3D low-temperature deposition printing honeycomb-shaped Poly(lactic-co-glycolic acid)/β-tricalcium phosphate icaritin (PTI) outer layer, maintaining the mechanical strength(elastic modulus ∼0.8 MPa) and osteogenic activity required for bone defect repair. Its core encapsulates hyaluronic acid (HA) hydrogel loaded with vancomycin(Van), serving as an intelligent "enzyme-responsive" unit. This core design utilizes bacterial-secreted hyaluronidase (HAase) at the infection site as a trigger signal, enabling on-demand, intelligent release of Van akin to the beehive sensing threats, while degrading slowly in the absence of infection, thereby achieving precise prevention of post-implantation infections. In vitro and in vivo results confirmed the scaffold's excellent dynamic responsive antibacterial performance, effectively eliminating target pathogens. Simultaneously, the hydrogel inner layer exhibited outstanding biocompatibility, synergistically promoting the proliferation, migration, and in vitro osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs). In a rabbit tibial defect infection model, the scaffold successfully mimicked the beehive's active defense mechanism, effectively suppressing Methicillin-resistant <i>Staphylococcus aureus</i> (<i>MRSA</i>) infection within 14 days post-implantation, achieveing simultaneous and ideal bone repair outcomes.