pH-Responsive ECM Coating on Ti Implants for Antibiosis in Reinfected Models.

Reinfection of implants during their service life causes troubles to patients. Traditionally, physical loading or chemical bonding of antibacterial agents on implant surfaces cannot settle the repeated bacterial invasion after a period of implantation. In this work, a pH-responsive extracellular matrix (ECM) coating was fabricated on Ti. It consisted of hydroxyapatite (HA) nanorods, antimicrobial peptide (AMP) cross-linked collagen I nanonets (CA nanonets), and physically loaded AMPs. CA nanonets formed in the interspaces of HA nanorods and had an average pore size of 46.5 nm. With the increase in the weight ratio of AMP cross-linkers in collagen I (from 0 to 1:3), the isoelectric points of CA nanonets increased. CA nanonets linked with 50 wt % of AMPs (HCA1) had an isoelectric point of about 7, and their zeta potential shifted from electronegativity to electropositivity when the pH value changed from 7.4 to 6.0. Compared with other nanonets, HCA1 showed a pH-responsive blast release of physically loaded AMPs. It was due to the electrostatic repulsion between the physically adsorbed AMPs and HCA1 after a shift in the potential. In vitro, all the CA nanonets were cytocompatible and exhibited significant short-term antibacterial performance; however, just HCA1 showed outstanding long-time responsive antibacterial activity; in vivo, HCA1 inhibited bacterial infection and suppressed the inflammatory response, especially in a reinfected model, indicating its potential application in Ti implants to mitigate the risk of reinfection.