Evaluation of a novel reconstituted bone xenograft using processed bovine cancellous bone in combination with purified bovine bone morphogenetic protein

Xenotransplantation. 2012 Mar-Apr;19(2):122-32. doi: 10.1111/j.1399-3089.2012.00694.x.

Abstract

Background: Xenogeneic grafting represents an alternative to autogenous grafting in osseous reconstruction and exhibits many beneficial properties. However, the usefulness of xenogeneic bone relies on necessary processing procedures for removing antigens and viruses, and preserving biological activities simultaneously. By chemical treatment of bovine cancellous bone to make it an antigen-free scaffold, and extraction of bone morphogenetic protein (BMP) from bovine cortical bone, followed by recombination of the scaffold with the BMP, we developed a new grafting material, reconstituted bone xenograft (RBX).

Methods: In this study, scanning electron microscope and energy dispersive X-ray were first employed to observe the structure and components of RBX. Then the biomechanical property was evaluated by applying compression in a materials testing machine. Subsequently, the immunologic evaluation was performed by measuring galactose-alpha-1,3-galactose (α-gal) epitope in vivo and proinflammatory cytokine (TNF-α) secreted by human monocytic cell line (THP-1) in vitro. Finally, this RBX was implanted into segmental radial defects in a rabbit model, and its ability to treat large bone defects was specifically evaluated.

Results: Although the compressive strength of RBX was 10% lower than that of unprocessed bovine cancellous bone (UBCB), the basic porous structure and natural components were still kept in this composite. The α-gal xenoantigen level was significantly lower in RBX (P < 0.05) compared with UBCB. Moreover, the TNF-α level was significantly (P < 0.05) reduced compared with UBCB when THP-1 was exposed to RBX. On the other hand, RBX appeared to induce cartilage formation from immature cell populations and resulted in osteogenesis through endochondral-like ossification from 4 to 12 weeks in repairing segmental bone defects.

Conclusions: These results demonstrate that RBX, with its natural microstructure and components, certain mechanical strength and strong osteoinductivity without evoking immune rejection, has significant potential for the treatment of bone defects.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Morphogenetic Proteins / isolation & purification
  • Bone Substitutes / chemistry
  • Bone Transplantation / immunology
  • Bone Transplantation / methods*
  • Bone Transplantation / physiology
  • Cattle
  • Graft Rejection / prevention & control
  • Humans
  • Male
  • Materials Testing
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Rabbits
  • Tissue Scaffolds* / chemistry
  • Transplantation, Heterologous / immunology
  • Trisaccharides / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Bone Morphogenetic Proteins
  • Bone Substitutes
  • Trisaccharides
  • Tumor Necrosis Factor-alpha
  • alpha-galactosyl epitope