Abstract
Additive manufacturing (AM) of titanium alloys offers the capacity to fabricate patient‐specific implants with defined porous architecture to enhance bone‐implant fixation. However, clinical challenges associated with orthopedic implants include inconsistent osseointegration and biofilm‐associated peri‐implant infection, leading to implant failure. Here, a strategy is developed to reduce infection and promote osteogenesis simultaneously on AM Ti‐6Al‐4V implants by delivering biofilm inhibitor molecules via titania nanotube surface modification. Electrochemical anodization is performed on polished and as‐manufactured Ti‐6Al‐4V to generate nanotubes, which are utilized for delivery of a novel methylthioadenosine nucleosidase inhibitor (MTANi) that targets MTAN—a key enzyme in bacterial metabolism involved in biofilm formation—thereby offering biofilm inhibition capacity combined with surface nano‐topography for promoting osteogenesis. Clinical isolates of staphylococcus cohnii formed firm biofilms on polished and AM Ti‐6Al‐4V controls whereas modified implants loaded with MTANi inhibit biofilm formation. Anodized AM Ti‐6Al‐4V nanotube substrates enhance alkaline phosphatase production, bone‐specific protein expression (osteocalcin, collagen I) and mineral deposition of human mesenchymal stromal cells (hMSCs), compared to as‐manufactured controls. Importantly, no detrimental effects on hMSC proliferation and osteogenic differentiation are observed for MTANi‐loaded substrates. Application of novel MTANi and electrochemical anodization offers a promising strategy for titanium alloy implant surface modification.
This study investigates the delivery of novel biofilm inhibitor (methylthioadenosine nucleosidase inhibitor (MTANi)) molecules through well‐organized titania nanotubes generated by electrochemical anodization on additive manufactured (AM) Ti‐6Al‐4V construct surfaces. Anodized AM Ti‐6Al‐4V substrates incorporating MTANi enable the simultaneous promotion of biofilm inhibition in clinical isolates of Staphylococcus cohnii as well as micro‐/nano‐topography mediated osteogenic differentiation of human mesenchymal stromal cells in vitro.