In vivo response to biodegradable controlled antibiotic release systems

Korkusuz F., Korkusuz P., Eksioglu F., Gursel I., Hasirci V.

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, vol.55, no.2, pp.217-228, 2001 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 2
  • Publication Date: 2001
  • Doi Number: 10.1002/1097-4636(200105)55:2<217::aid-jbm1008>;2-p
  • Journal Indexes: Science Citation Index Expanded
  • Page Numbers: pp.217-228
  • Keywords: osteomyelitis, sustained release, local antiinfective agents, biodegradable delivery systems, polymers, poly(hydroxybutyrate-co-hydroxyvalerate), LACTIC-ACID POLYMERS, STAPHYLOCOCCAL OSTEOMYELITIS, DELIVERY SYSTEM, DRUG-RELEASE, IN-VITRO, BIOCOMPATIBILITY, HYDROXYAPATITE, POLYHYDROXYBUTYRATE, COPOLYMERS, INVITRO


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(3HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy-valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone(R) and the Duocid(R)-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(R)- and Sulperazone(R)-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(R)-P(3-HB-co-4-HB) and Duocid(R)-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. (C) 2001 John Wiley & Sons, Inc.