Combined Infection Control and Enhanced Osteogenic Differentiation Capacity on Additive Manufactured Ti-6Al-4V are Mediated via Titania Nanotube Delivery of Novel Biofilm Inhibitors

Jun Li, Isha Mutreja, Gary J. Hooper, Keith Clinch, Khoon Lim, Gary Evans, Tim B.F. Woodfield*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Article number1901963
JournalAdvanced Materials Interfaces
Volume7
Issue number7
DOIs
StatePublished - 1 Apr 2020
Externally publishedYes

Keywords

  • Ti-6Al-4V
  • additive manufacture
  • biofilm inhibition
  • electrochemical anodization
  • osteogenesis

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