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.