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.
Elderly patients predispose to cardiovascular implantable electronic devices (CIEDs) pocket infections due to multiple comorbidities. Treating infections with the antibiotics further carry higher risks for complications, and surgical intervention can be costly when device removal and reimplantation are required, both emphasizing the importance of novel preventive strategies to minimize the incidence of pocket infections. To meet the unique needs for elderly, we constructed an CIED surface modified hydrogel which crosslinked polyethylene glycol diacrylate (PEGDA) with hyaluronic acid-nitrobenzene (HN) to form the polymeric structures that mimic the natural environment for promoting “Pocket” surrounding tissue integration and healing. Importantly, we synthesized the new peptidomimetics FK-13 derived by shortening amino acid sequence of LL-37 which is the only human cathelicidin-derived antimicrobial peptide. By incorporating FK-13 with initial PN hydrogel via Schiff base formation, the created PN-FK hydrogel exhibited broad-spectrum antimicrobial activity against bacteria with excellent biocompatibility and mechanical properties in a long-term release manner. In an in vitro setting, PN-FK hydrogel demonstrated the regeneration capacity by expression of Hmox1, Col5 and Col6 associated genes in fibroblasts as well as expression of Gpx1, Cdc20 and MMP9 genes in stem cells to accelerate self-renewal, collagen secretion and reconstitution of matrix components. In the following in vivo model of subcutaneous implantation, CIED-shape titanium mesh with surface modification by PN-FK hydrogel efficiently subsided over-inflammation compared to bare titanium implant, and expedited collagen deposition and angiogenesis in peri -pocket tissues within 2 weeks. These findings underscore the potential of the PN-FK hydrogel as a transformative approach to CIED postoperative management, offering a dual-action solution that combines infection resistance with tissue regeneration capabilities.
危险品化学品经营许可证（带存储）