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

Research output: Contribution to journalArticlepeer-review

8 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 (US)
Article number1901963
JournalAdvanced Materials Interfaces
Volume7
Issue number7
DOIs
StatePublished - Apr 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to acknowledge funding from the Ministry of Business, Innovation & Employment (MBIE-UOOX1407; T.W.), the Royal Society of New Zealand Rutherford Discovery Fellowship (RDF-UOO1204; T.W.), and the New Zealand Medical Technologies Centre of Research Excellence (MedTech CoRE).

Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

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

Fingerprint

Dive into the research topics of 'Combined Infection Control and Enhanced Osteogenic Differentiation Capacity on Additive Manufactured Ti-6Al-4V are Mediated via Titania Nanotube Delivery of Novel Biofilm Inhibitors'. Together they form a unique fingerprint.

Cite this