Multidimensional treatment of periprosthetic joint infection using fusion peptide-grafted chitosan coated porous tantalum scaffold

Abstract

Bacterial infection and delayed osteointegration are two major challenges for orthopedic implants. Surface modification enables the implant have a time-sequenced biological function of effective antibacterial in the early stage and stable osteogenesis in the later stage, which is expected to achieve the purpose of preventing infection and prosthetic loosening after implant surgery. This study aims to construct a composite coating of carboxymethyl chitosan (CCS) grafted with an antibacterial (HHC36) and angiogenic (FP) fusion peptide (FP) on the surface of 3D-printed porous tantalum (Ta-CCS@FP) using alkaline treatment, electrostatic adsorption, and EDC/NHS reaction, to functionalize the surface coating while maintaining the original advantages of the material. The functionalized implants (Ta-CCS@FP) achieve sustained FP release in the initial stages, exhibiting potent antibacterial and anti-biofilm properties due to the synergistic action of the antimicrobial peptides (AMPs) HHC36 and CCS in disrupting bacterial membranes. Additionally, Ta-CCS@FP demonstrate robust osteogenic and angiogenic capabilities compared to Ta and Ta-CCS, attributed to QK and CCS. Notably, the conditioned medium intervention experiments of HUVECs and BMSCs showed that the implants had good angiogenic-osteogenic coupling properties. In vivo assays using infection bone defect models revealed that these bioactive implants effectively eradicated bacteria within 2 weeks and facilitated vascularized bone regeneration by 6 weeks. Thus, our study offers an integrated approach to address bacterial infection and enhance osseointegration for porous tantalum implants.