Novel Therapeutic Strategy for Bacteria‐Contaminated Bone Defects: Reconstruction with Multi‐Biofunctional GO/Cu‐Incorporated 3D Scaffolds

Large-scale bone defects caused by traumatic injury or tumor resection, are accompanied by relatively high bacterial infection rates. Relevant clinical therapy encounters challenges of infection recurrence, poor vascularization, and bone destruction. Engineered substitutes endowed with multiple functions of bacterial eradication, osteoconductivity, and angiogenesis are urgently needed to address these challenges. Herein, graphene oxide/copper (GO/Cu) nanocomposite-decorated polylactide-co-glycolide (PLGA)/beta-tricalcium phosphate (TCP) (P/T/GO/Cu) scaffolds are fabricated using 3D printing technology. A comprehensive evaluation of material characteristics and biological activities of these scaffolds is conducted and compared. This novel bone substitute has unique surface characteristics, and the incorporation of GO/Cu nanocomposites into the scaffolds exhibits improved antimicrobial and osteogenic potential and displays acceptable cytocompatibility. A subcutaneous implantation model in rats confirms the effective inhibition of abscess formation and inflammatory reactions, satisfactory neovascularization and tissue integration, and good biosafety of the implanted P/T/GO/Cu scaffolds. Eventually, a bacteria-contaminated bone defect model is established in rabbits and significantly better new cancellous bone formation featuring collagen or osteoid deposition is clearly found in the defect regions implanted with P/T/GO/Cu scaffolds. Thus, this novel bone substitute with excellent bacterial inhibition, osteogenesis, and angiogenesis capabilities represents a promising strategy to satisfy the multiple demands for the repair of bacteria-contaminated bone defects.