A bioswitchable antibacterial strategy for the treatment of implant-associated infections

Abstract

Implant-associated infection (IAI) remains a significant clinical challenge due to the increase of bacterial resistance and the presence of bacterial biofilm. Endowing implants with antibacterial properties and functionality by surface covalent immobilization of antimicrobial peptides (AMPs) is a highly promising approach, but suffers from poor antibacterial effect. In this study, a bioswitchable antibacterial system is flexibly designed and constructed for IAI therapy. A universal and functional coating is polymerized on the material surface by propionaldehyde plasma polymerization and then conjugated with LL-37, a human cathelicidin peptide, by Schiff base reaction. The release of LL-37 can be triggered by the acidic microenvironment results from bacterial metabolism and respiration. The conjugated LL-37 under physiological environment shows better biocompatibility than direct administration of LL-37, while responsive released LL-37 under acidic microenvironment exhibits preferrable antibacterial activity in comparison with unresponsive immobilization of LL-37. Besides, the bioswitchable coating exhibits variable immunomodulatory abilities. Further in vivo subcutaneous implant-associated infection model confirms the good protection against bacterial infection of bioswitchable antibacterial system. This design strategy of bioswitchable antibacterial system will provide a simple and universal approach for the prevention and therapy of implant-associated infection.