Enzyme responsive titanium substrates with antibacterial property and osteo/angio-genic differentiation potentials

After implantation into a host, titanium (Ti) orthopaedic materials are facing two major clinical challenges: bacterial infection and aseptic loosening, which directly determine the long-term survival of the implant. To endow Ti implant with self-defensive antibacterial properties and desirable osteo/angio-genic differentiation potentials, hyaluronic acid (HA)-gentamicin (Gen) conjugates (HA-Gen) and chitosan (Chi) polyelectrolyte multilayers were constructed on deferoxamine (DFO) loaded titania nanotubes (TNT) substrates via layer-by-layer (LBL) assembly technique, termed as TNT/DFO/HA-Gen. The HA-Gen conjugate was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (¹H NMR). The physicochemical properties of the substrates were characterized by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The on-demand DFO release was associated with the degradation of multilayers triggered by exogenous hyaluronidase, which indicated enzymatic and bacterial responsiveness. The TNT/DFO/HA-Gen substrates displayed effective antifouling and antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), while were favourable for the adhesion, proliferation and osteo/angio-genic differentiation of mesenchymal stem cells (MSCs). The multifaceted drug-device combination (DDC) strategy showed potential applications in orthopaedic fields.