Radical-enabled immobilization of CR-171 peptides on PCL implants to prevent infection

Implant-associated infections remain a critical challenge in orthopedic surgery, as current antibacterial strategies often compromise osseointegration and tissue regeneration. Antimicrobial coating strategies for biodegradable 3D scaffolds are limited by burst-release behavior, weak peptide retention, multi-step wet chemistry, or inability to uniformly functionalize complex porous architectures. Here, we used packed-bed plasma ion implantation (PBPII) to stably immobilize, consistent with covalent attachment, the cationic antimicrobial peptide CR-171 onto 3D-printed polycaprolactone (PCL) scaffolds without linker molecules. Surface analyses were consistent with nitrogen implantation, radical generation, and peptide immobilization, while wettability measurements showed increased hydrophilicity after PBPII treatment. Peptide loading and retention after detergent challenge were markedly higher on treated than physically adsorbed scaffolds. CR-171-functionalized scaffolds exhibited strong antibacterial activity against Staphylococcus aureus and Escherichia coli , with >99% and approximately 95% inhibition, respectively, corroborated by SEM imaging. Human mesenchymal stromal cells retained high viability and well-spread cytoskeletal organization, while a separate whole-blood assay showed no significant differences in IL-6 or TNF-α secretion between scaffold groups. Under osteogenic conditions, mineralization was comparable to unmodified PCL, confirming the coating did not impair osteogenic differentiation. Overall, PBPII-mediated CR-171 immobilization yields biocompatible, infection-resistant PCL scaffolds and represents a promising platform for antibacterial polymeric implants and bone graft substitutes.