Xenotransplantation. 2020;00:e12662. | 1 of 11 https://doi.org/10.1111/xen.12662 wileyonlinelibrary.com/journal/xen Received: 4 May 2020 | Revised: 4 October 2020 | Accepted: 9 November 2020 DOI: 10.1111/xen.12662 ORIGINAL ARTICLE Improved osseointegration using porcine xenograft compared to demineralized bone matrix for the treatment of critical defects in a small animal model Alexander H. Jinnah 1 | Patrick Whitlock 2 | Jeffrey S. Willey 3 | Kerry Danelson 1 | Bethany A. Kerr 1,4 | Omer A. Hassan 5 | Cynthia L. Emory 1 | Thomas L. Smith 1 | Daniel N. Bracey 1 © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. 1 Division of Orthopaedic Surgery, Wake Forest Baptist Medical Center, Winston- Salem, NC, USA 2 Division of Pediatric Orthopaedics, Cincinnati Children's Hospital, Cincinnati, OH, USA 3 Department of Radiation/Oncology, Wake Forest Baptist Medical Center, Winston- Salem, NC, USA 4 Department of Cancer Biology, Wake Forest Baptist Medical Center, Winston- Salem, NC, USA 5 Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA Correspondence Alexander H. Jinnah, Division of Orthopaedic Surgery, Wake Forest Baptist Medical Center, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA. Email: ajinnah@wakehealth.edu Funding information Orthopaedic Research and Education Foundation, Grant/Award Number: 17-057 Abstract Background: Autograft (AG) is the gold standard bone graft due to biocompatibil- ity, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include al- lografts and xenografts (XG). Methods: We investigated the osseointegration and biocompatibility of a decellu- larized 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 meas- ured from animal blood draws at 1 week and 1 month post-operatively. At 1 month, samples underwent micro-positron-emission tomography (microPET) scans following 18-NaF injection. At 16 weeks, femurs were retrieved and sent for micro-comput- erized tomography (microCT) scans for blinded grading of osseointegration or were processed for histologic analysis with tartrate resistant acid phosphatase (TRAP) and pentachrome. Results: Enzyme linked immunosorbent assay testing demonstrated greater IL-2 lev- els in the XG vs. AG 1 week post-op; which normalized by 28 days 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 com- pared to DBM. Pentachrome staining demonstrated angiogenesis and endochondral bone formation. Furthermore, positive TRAP staining in samples from all groups in- dicated bone remodeling. Conclusions: These data suggest that decellularized and oxidized porcine XG is bio- compatible and at least equivalent to DBM in the treatment of a critical defect in a rat femur model.