Vancomycin-laden calcium phosphate-calcium sulfate composite allows bone formation in a rat infection model

PLoS One. 2019 Sep 19;14(9):e0222034. doi: 10.1371/journal.pone.0222034. eCollection 2019.

Abstract

Objective: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model.

Methods: Sixty-four, male Sprague-Dawley rats were inoculated with 10 μl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology.

Results: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups.

Conclusions: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / pharmacology
  • Calcium Phosphates / administration & dosage*
  • Calcium Phosphates / pharmacology
  • Calcium Sulfate / administration & dosage*
  • Calcium Sulfate / pharmacology
  • Disease Models, Animal
  • Humans
  • Male
  • Osteogenesis / drug effects
  • Osteomyelitis / diagnostic imaging
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / microbiology
  • Osteomyelitis / prevention & control
  • Polymethyl Methacrylate / administration & dosage*
  • Polymethyl Methacrylate / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / diagnostic imaging
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / isolation & purification
  • Treatment Outcome
  • Vancomycin / administration & dosage*
  • Vancomycin / chemistry
  • Vancomycin / pharmacology
  • X-Ray Microtomography

Substances

  • Biocompatible Materials
  • Calcium Phosphates
  • Vancomycin
  • Polymethyl Methacrylate
  • calcium phosphate
  • Calcium Sulfate