A porcine xenograft-derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha-Gal epitope

Daniel N. Bracey, Thorsten M. Seyler, Alexander H. Jinnah, Thomas L. Smith, David A. Ornelles, Rajendar Deora, Griffith D. Parks, Mark E. Van Dyke, Patrick W. Whitlock

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Xenografts are an attractive alternative to traditional bone grafts because of the large supply from donors with predictable morphology and biology as well as minimal risk of human disease transmission. Clinical series involving xenograft bone transplantation, most commonly from bovine sources, have reported poor results with frequent graft rejection and failure to integrate with host tissue. Failures have been attributed to residual alpha-Gal epitope in the xenograft which humans produce natural antibody against. To the authors' knowledge, there is currently no xenograft-derived bone graft substitute that has been adopted by orthopedic surgeons for routine clinical use. Methods: In the current study, a bone scaffold intended to serve as a bone graft substitute was derived from porcine cancellous bone using a tissue decellularization and chemical oxidation protocol. In vitro cytocompatibility, pathogen clearance, and alpha-Gal quantification tests were used to assess the safety of the bone scaffold intended for human use. Results: In vitro studies showed the scaffold was free of processing chemicals and biocompatible with mouse and human cell lines. When bacterial and viral pathogens were purposefully added to porcine donor tissue, processing successfully removed these pathogens to comply with sterility assurance levels established by allograft tissue providers. Critically, 98.5% of the alpha-Gal epitope was removed from donor tissue after decellularization as shown by ELISA inhibition assay and immunohistochemical staining. Conclusions: The current investigation supports the biologic safety of bone scaffolds derived from porcine donors using a decellularization protocol that meets current sterility assurance standards. The majority of the highly immunogenic xenograft carbohydrate was removed from donor tissue, and these findings support further in vivo investigation of xenograft-derived bone tissue for orthopedic clinical application.

Original languageEnglish (US)
Article numbere12534
JournalXenotransplantation
Volume26
Issue number5
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

Keywords

  • alpha-gal
  • bone graft
  • bone scaffold
  • xenograft
  • xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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