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.