Preclinical induced membrane model to evaluate synthetic implants for healing critical bone defects without autograft.

Critical bone defects pose a formidable orthopaedic problem in patients with bone loss. We developed a preclinical model based on the induced membrane technique using a synthetic graft to replace autograft for healing critical bone defects. Additionally, we used a novel osteoconductive scaffold coupled with a synthetic membrane to evaluate the potential for single-stage bone regeneration. Three experimental conditions were investigated in critical femoral defects in rats. Group A underwent a two-stage procedure with insertion of a polymethylmethacrylate (PMMA) spacer followed by replacement with a 3D printed polycaprolactone(PCL)/β-tricalcium phosphate (β-TCP) osteoconductive scaffold after 4 weeks. Group B received a single-stage PCL/β-TCP scaffold wrapped in a PCL-based microporous polymer film creating a synthetic membrane. Group C received a single-stage bare PCL/β-TCP scaffold. All groups were examined by serial radiographs for callus formation. After 12 weeks, the femurs were explanted and analyzed with micro-CT and histology. Mean callus scores tended to be higher in Group A. Group A showed statistically significant greater bone formation on micro-CT compared with other groups, although bone volume fraction was similar between groups. Histology results suggested extensive bone ingrowth and new bone formation within the macroporous scaffolds in all groups and cell infiltration into the microporous synthetic membrane. This study supports the use of a critical size femoral defect in rats as a suitable model for investigating modifications to the induced membrane technique without autograft harvest. Future investigations should focus on bioactive synthetic membranes coupled with growth factors for single-stage bone healing.