Coordination-Driven Cu²⁺-Peptide Supramolecular Hydrogel-PCL Scaffold for Synergistic Antibacterial Activity and Osteogenic Regeneration in Infectious Bone Defects.

Abstract

Infectious bone defects, characterized by persistent bacterial infection and impaired osteogenesis, remain a major clinical challenge. Here, a copper ion-peptide supramolecular hydrogel integrated with a 3D-printed polycaprolactone scaffold (CPSH@PCL) was developed for synergistic treatment of infectious bone defects. Cu²⁺-mediated peptide coordination formed a stable nanofibrous network, enabling robust scaffold coating, enhanced mechanical support, and sustained Cu²⁺ release under both physiological and infection-associated mildly acidic conditions. CPSH@PCL exhibited potent broad-spectrum antibacterial and antibiofilm activity (>99% against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa) and disrupted mature biofilms. It also scavenged reactive oxygen species and catalyzed oxygen generation, alleviating infection-induced oxidative stress and hypoxia. At the cellular level, CPSH@PCL promoted proliferation and migration of bone marrow mesenchymal stem cells and osteoblasts, while markedly enhancing osteogenic differentiation through activation of HIF-1α-mediated aerobic glycolysis. In a rat cranial defect model, CPSH@PCL suppressed infection, significantly increased bone mineral density and bone volume fraction, and accelerated new bone formation with upregulated osteocalcin. This work demonstrated a metal ion-driven peptide self-assembly strategy that integrated antibacterial, antioxidant, and osteogenic functions in a single scaffold, offering a multifunctional biomaterial platform for treating complex infectious bone defects.