Antibiotic-Loaded Polymer-Calcium Phosphate Scaffold for Treating Orthopedic Device-Related Infection in a Rabbit Segmental Bone Defect Model

Abstract

Treatment of orthopedic device-related infection (ORDI) generally requires a combination of medical and surgical interventions for successful treatment outcomes. Many cases are treated with a two-stage revision, whereby contaminated implants and necrotic tissues are removed, and dead space is managed with a temporary, non-resorbable polymethyl methacrylate (PMMA) spacer loaded with antibiotics. Weeks later, this is replaced with a bone graft or similar material to aid bone healing. However, this two-stage approach is quite a burden for the patient, and infection may still recur. The use of a 3D-printed, absorbable, antibiotic-releasing material that also promotes bone healing would be a promising alternative that produces the exact geometry of the missing bone and eliminates the need for a second surgery. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoconductive calcium phosphate scaffold (CPS) is effective in the single-stage revision of an infected segmental bone defect model in rabbits. A 5-mm segmental defect of the radius of female New Zealand White rabbits (n = 64), stabilized with cerclage wire, was inoculated with Staphylococcus aureus. After 4 weeks, the infected bone fragment was removed, the site debrided, and the bone defect was either left empty (Control group) or filled with a PMMA spacer with gentamicin, CPS loaded with rifampicin or non-loaded CPS. The animals were also managed with systemic cefazolin for 4 weeks. An additional group received vancomycin-loaded CPS without adjunctive systemic antibiotic therapy. All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or semiquantitative histopathology. The antibiotic-loaded scaffolds (PMMA-Genta and CPS-Rif) in the animals receiving systemic antibiotic treatment resulted in a reduction in bacterial count at euthanasia compared to controls (rabbits receiving systemic antibiotic alone and in which the defect was left empty). The PMMA-Genta induced a significant CFU reduction (p = 0.0486) compared to controls. The infection rate was also reduced from 80% in the control group to 50% for the groups receiving local and systemic antibiotics. The CPS-Vanco group for local delivery without adjunctive systemic antibiotic therapy resulted in a lower infection rate, but the CFUs in these samples at euthanasia were comparable with those of the control group. The findings show that treating an ODRI with PMMA-Genta yields the best results for infection eradication; however, it does not provide the reconstruction opportunity that the antibiotic-loaded CPS does. Even though it is not comparable to the PMMA-Genta, the antibiotic-loaded CPS showed a reduction in infection rates. The use of local antibiotics alone is insufficient to eradicate the infection.