Copper-containing chitosan-based hydrogels enabled 3D-printed scaffolds to accelerate bone repair and eliminate MRSA-related infection

Bone defect combined with drug-resistant bacteria-related infection is a thorny challenge in clinic. Herein, 3D-printed polyhydroxyalkanoates/β-tricalcium phosphate (PHA/β-TCP, PT) scaffolds were prepared by fused deposition modeling. Then copper-containing carboxymethyl chitosan/alginate (CA/Cu) hydrogels were integrated with the scaffolds via a facile and low-cost chemical crosslinking method. The resultant PT/CA/Cu scaffolds could promote not only proliferation but also osteogenic differentiation of preosteoblasts in vitro. Moreover, PT/CA/Cu scaffolds exhibited a strong antibacterial activity towards a broad-spectrum of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) through inducing the intercellular generation of reactive oxygen species. In vivo experiments further demonstrated that PT/CA/Cu scaffolds significantly accelerated bone repair of cranial defects and efficiently eliminated MRSA-related infection, showing potential for application in infected bone defect therapy.