Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections.
Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. The objective of this study was to develop a technique that enables the loading and local delivery of a unique group of cationic antimicrobial peptides (AMP) through implant surfaces. A thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The broad spectrum AMP Tet213 (KRWWKWWRRC) was selected and loaded onto the CaP coating. SEM, XRD and FTIR analyses confirmed the CaP coating to be micro-porous octacalcium phosphate. By using a luminescence spectrometer technique, it was demonstrated that a 7 μm thick porous CaP coating could load up to 9 μg of AMP/cm² using a simple soaking technique. The drug-loaded CaP coating (CaP-Tet213) was not cytotoxic for MG-63 osteoblast-like cells. The CaP-Tet213 implants had antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 10⁶-fold reductions of both bacterial strains within 30 min as assessed by measuring colony-forming units (CFU). Repeated CFU assays on the same CaP-Tet213 specimen demonstrated retention of antimicrobial activity by the CaP-Tet213 surfaces through four test cycles. The susceptibility of bacteria to the CaP-Tet213 surfaces was also evaluated by assessing the inhibition of luminescence of P. aeruginosa containing a luxCDABE cassette at 4 h and 24 h with ∼92% and ∼77% inhibition of luminescence, respectively. It was demonstrated that CaP-Tet213 was a more efficient antimicrobial coating than CaP-MX226, CaP-hLF1-11 or CaP-tobramycin following incubation of CaP implants with equimolar concentrations of Tet213, the commercially developed antimicrobial peptide MX-226, hLF1-11 or tobramycin. A device coated with CaP-Tet213 could be a potential solution for the prevention of the peri-implant infection in orthopaedics.
Department of Materials Engineering, University of British Columbia, 309 - 6350 Stores Road, Vancouver, BC, V6T 1Z4, Canada.
Mehdi
M
Kazemzadeh-Narbat
Jason
J
Kindrachuk
Ke
K
Duan
Håvard
H
Jenssen
Robert E W
RE
Hancock
Rizhi
R
Wang
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death; D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D019736:Prostheses and Implants / Q000009:adverse effects*; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014025:Titanium / Q000494:pharmacology / Q000627:therapeutic use*; D014961:X-Ray Diffraction
D023181:Antimicrobial Cationic Peptides; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D055767:Immobilized Proteins; D014025:Titanium