Covalent grafting of titanium with a cathelicidin peptide produces an osteoblast compatible surface with antistaphylococcal activity

Colloids Surf B Biointerfaces. 2020 Jan 1:185:110586. doi: 10.1016/j.colsurfb.2019.110586. Epub 2019 Oct 16.

Abstract

Bacterial infection of orthopaedic implants, often caused by Staphylococcus species, may ultimately lead to implant failure. The development of infection-resistant, osteoblast-compatible biomaterials could represent an effective strategy to prevent bacterial colonization of implants, reducing the need for antibiotics. In this study, the widely used biomaterial titanium was functionalized with BMAP27(1-18), an α-helical cathelicidin antimicrobial peptide that retains potent staphylocidal activity when immobilized on agarose beads. A derivative bearing a short spacer with a free thiol at the N-terminus was coupled to silanized titanium disks via thiol-maleimide chemistry. Tethering was successful, as assessed by Contact angle, Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), and X-ray Photoelectron Spectroscopy (XPS), with an average surface mass density of 456 ng/cm2 and a layer thickness of 3 nm. The functionalized titanium displayed antimicrobial properties against a reference strain of Staphylococcus epidermidis with well-known biofilm forming capability. Reduction of bacterial counts and morphological alterations of adhering bacteria, upon 2 h incubation, indicate a rapid contact-killing effect. The immobilized peptide was not toxic to osteoblasts, which adhered and spread better on functionalized titanium when co-cultured with bacteria, compared to non-coated surfaces. Results suggest that functionalization of titanium with BMAP27(1-18) could be promising for prevention of bacterial colonization in bone graft applications.

Keywords: Alpha-helical antimicrobial peptide; Biofunctionalization; Osteoblast-bacteria co-culture; Osteoblasts; Staphylococcus epidermidis; Titanium.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Adhesion / drug effects*
  • Cathelicidins
  • Cell Proliferation
  • Cells, Cultured
  • Coated Materials, Biocompatible / chemistry*
  • Coculture Techniques
  • Humans
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / growth & development*
  • Surface Properties
  • Titanium / chemistry*

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Coated Materials, Biocompatible
  • Titanium
  • Cathelicidins