Self-protecting bactericidal titanium alloy surface formed by covalent bonding of daptomycin bisphosphonates

Bioconjug Chem. 2010 Nov 17;21(11):1978-86. doi: 10.1021/bc100136e. Epub 2010 Oct 15.

Abstract

Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm² Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol/cm². Daptomycin-bonded foils killed 53 ± 5% of a high challenge dose of 3 × 10⁵ cfu Staphylococcus aureus ATCC 29213.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys / chemistry*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Daptomycin / analogs & derivatives
  • Daptomycin / chemistry
  • Daptomycin / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Staphylococcus aureus / drug effects*
  • Surface Properties
  • Titanium / chemistry*

Substances

  • Alloys
  • Anti-Bacterial Agents
  • Titanium
  • Daptomycin