A HAase/NIR responsive surface on titanium implants for treating bacterial infection and improving osseointegration

Abstract

• A mild antibacterial system for S. aureus and MRSA was constructed based on the synergistic effect of photothermal and antibiotic. • Antibiotic in MPDA can be sealed with HAc, which can avoid the damage to normal tissue caused by the burst release CIP and inhibit the early adhesion of bacteria. • Bacteria can secrete bacterial hyaluronidase to accelerate the degradation of HAc, realizing the smart enzyme-triggered release of antimicrobials at the site of infection on demand. • NIR light irradiation can not only accelerate the CIP release but also activate the photothermotherapy of MPDA nanoparticles. Bacterial infection and insufficient osseointegration are critical factors affecting the long-term success of titanium-based implants. Unfortunately, the direct application of antibiotic on Ti implants easily leads to poor cytocompatibility, as well as the production of drug-resistant bacteria. So, in this work, we designed a prospective antibacterial strategy by combining photothermal and ciprofloxacin (CIP). The synergistic effect of photothermal and antibiotic may provide an effective bacteriostatic efficacy without sacrificing osteogenesis at a mild condition of moderate temperature and less antibiotic. Herein, CIP was loaded into mesoporous polydopamine (MPDA) nanoparticles (MPDA@CIP), which were anchored on the surface of titanium and finally covered with sodium hyaluronate-catechol (HAc) coating. The hydrophilic HAc layer could inhibit the early adhesion of bacteria, and some bacteria could secrete bacterial hyaluronidase to accelerate the degradation of HAc. This enabled smart enzyme-triggered release of antimicrobials at the site of infection on-demand and avoided unwanted side effects on normal tissues. In addition, NIR light irradiation had a positive influence on both CIP release and MPDA nanoparticle's photothermal effect. Moreover, before anchoring MPDA@CIP, by the construction of hydroxyapatite microstructure on Ti surface with micro-arc oxidation and alkali heat treatment, the ability of bone formation of Ti could be promoted also. Both in vitro as well as in vivo assays demonstrated that functional Ti has an excellent antibacterial effect and osteogenic ability.