Hydroxyapatite microporous bioceramics as vancomycin reservoir: Antibacterial efficiency and biocompatibility investigation.
AbstarctInfections after bone reconstructive surgery are a real therapeutic and economic issue for the modern health care system. As the pathogen (most often Staphylococcus aureus) is able to develop a biofilm inside the bone, local delivery of antibiotics is of interest since high drug concentrations would be delivered directly at the target place. In this context, this study evaluated a porous hydroxyapatite implant as biocompatible bone substitute and vancomycin-delivery system to prevent post-operative infections. A simple method of impregnation with optimised conditions insured a high antibiotic loading (up to 2.3 ± 0.3 mg/m2), with a complete in vitro release obtained within 1-5 days. Additionally, the bacteriostatic and bactericidal effects of vancomycin were retained after loading on hydroxyapatite, as demonstrated after challenge with a Staphylococcus aureus strain. Regarding the biocompatibility, a wound healing assay of pre-osteoblastic MC3T3-E1 cells exposed to various concentrations of vancomycin revealed a dose-dependent reduction in cell migration for antibiotic concentrations higher than 1 mg/mL. Meanwhile, cells were able to proliferate normally on vancomycin-loaded scaffolds, although cell initial adhesion was seriously impaired for scaffolds loaded with 2.3 mg/m2Loaded scaffolds could be stored up to three months at room temperature without any degradation of the antibiotic. Together, these results demonstrate the efficacy of these hydroxyapatite bone substitutes for local delivery of vancomycin in the context of bone infection.
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France.
Marianne
M
Parent
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France.
Amandine
A
Magnaudeix
Univ. Limoges, Laboratoire de Chimie des Substances Naturelles, Limoges, France.
Sylvie
S
Delebassée
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France.
Elisabeth
E
Sarre
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France.
Eric
E
Champion
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France.
Marylène
M
Viana Trecant
Univ. Limoges, CNRS, ENSCI, SPCTS, UMR 7315, Limoges, France chantal.damia@unilim.fr.
Chantal
C
Damia
D065966:Absorption, Physicochemical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D041702:BALB 3T3 Cells; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects*; D002516:Ceramics / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis; D004058:Diffusion; D017886:Durapatite / Q000737:chemistry*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058608:Nanopores / Q000648:ultrastructure; D010316:Particle Size; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D014640:Vancomycin; D017886:Durapatite
Hydroxyapatite; bone tissue engineering; drug delivery; osteomyelitis; vancomycin