Improved osseointegration using porcine xenograft compared to demineralized bone matrix for the treatment of critical defects in a small animal model.

Abstract

Autograft (AG) is the gold standard bone graft due to biocompatibility, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include allografts and xenografts (XG). We investigated the osseointegration and biocompatibility of a decellularized porcine XG within a critical defect animal model. We hypothesized that the XG will result in superior osseointegration compared to demineralized bone matrix (DBM) and equivalent immune response to AG. Critical defects were created in rat femurs and treated with XG, XG plus bone morphogenetic protein (BMP)-2, DBM, or AG. Interleukin (IL)-2 and IFN-gamma levels (inflammatory markers) were measured from animal blood draws at 1week and 1month post-operatively. At 1month, samples underwent micro-positron-emission tomography (microPET) scans following 18-NaF injection. At 16weeks, femurs were retrieved and sent for micro-computerized tomography (microCT) scans for blinded grading of osseointegration or were processed for histologic analysis with tartrate resistant acid phosphatase (TRAP) and pentachrome. Enzyme linked immunosorbent assay testing demonstrated greater IL-2 levels in the XG vs. AG 1week post-op; which normalized by 28days post-op. MicroPET scans showed increased uptake within the AG compared to all groups. XG and XG+BMP-2 showed a trend toward increased uptake compared with DBM. MicroCT scans demonstrated increased osseointegration in XG and XG+BMP groups compared to DBM. Pentachrome staining demonstrated angiogenesis and endochondral bone formation. Furthermore, positive TRAP staining in samples from all groups indicatedbone remodeling. These data suggest that decellularized and oxidized porcine XG is biocompatible and at least equivalent to DBM in the treatment of a critical defect in a rat femur model.