In vivo response to biodegradable controlled antibiotic release systems

J Biomed Mater Res. 2001 May;55(2):217-28.

Abstract

In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy- valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone and the Duocid-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid- and Sulperazone-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. Inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone-P(3-HB-co-4-HB) and Duocid-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Biocompatible Materials*
  • Biodegradation, Environmental
  • Drug Delivery Systems*
  • Drug Implants*
  • In Vitro Techniques
  • Materials Testing
  • Osteomyelitis / drug therapy
  • Osteomyelitis / etiology
  • Osteomyelitis / pathology
  • Polymers
  • Prostheses and Implants / adverse effects
  • Prosthesis-Related Infections / drug therapy
  • Prosthesis-Related Infections / etiology
  • Prosthesis-Related Infections / pathology
  • Rabbits
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / etiology
  • Staphylococcal Infections / pathology

Substances

  • Anti-Bacterial Agents
  • Biocompatible Materials
  • Drug Implants
  • Polymers