Self-adaptive 3D-printed PCLA/BCP scaffolds functionalized using vapor etching and nanocoating for immunomodulatory and antibacterial bone regeneration

Integrating immunomodulatory and antibacterial functions into bone scaffolds is crucial for effective bone regeneration, especially in infection-prone clinical settings. This strategy enhances healing, reduces postoperative infection risk, and improves implant osseointegration. Here, we developed a 3D-printed scaffold with shape-memory, immunomodulatory, and antibacterial capabilities. The scaffold was fabricated by dissolving poly(caprolactone-co-lactic acid) in dioxane and incorporating biphasic calcium phosphate, followed by low-temperature 3D printing, freeze-drying, and surface etching with vapor-phase ethanol-acetic acid to enhance roughness. γ-Cyclodextrin/tea polyphenol-magnesium nanoparticles were then immobilized on the scaffold surface to create a pH-responsive system for dual sustained release. Tea polyphenols provided broad-spectrum antibacterial activity, including against methicillin-resistant Staphylococcus aureus, while Mg²⁺ promoted M2 macrophage polarization to modulate the immune microenvironment. Surface characterization confirmed enhanced hydrophilicity and cell adhesion. In vitro studies demonstrated inhibition of bacterial biofilms, along with improved cell proliferation and osteogenic differentiation. In vivo evaluation in an MRSA-infected rat femoral defect model showed reduced local inflammation and enhanced vascularized bone regeneration. This multifunctional scaffold design synergizes physical adaptability with bioactive regulation, offering a promising therapeutic strategy for the repair of infected bone defects. STATEMENT OF SIGNIFICANCE: This study introduces a self-adaptive 3D-printed scaffold designed for bone regeneration in infection-prone environments. Constructed from PCLA and BCP, the scaffold integrates shape memory properties with antibacterial and immunomodulatory functions. Incorporation of γ-cyclodextrin/tea polyphenol-magnesium complexes enables sustained, pH-responsive release of bioactive agents that suppress bacterial growth, promote angiogenesis, and induce M2 macrophage polarization. Vapor-phase etching enhances surface roughness and hydrophilicity, improving cellular adhesion and nutrient exchange. In vitro studies confirmed antibacterial efficacy, immune modulation, and osteogenic promotion, while in a rat MRSA-infected femoral defect model, the scaffold reduced inflammation, supported vascularized bone formation, and accelerated healing, highlighting its strong translational potential.