Effects of compatibility of deproteinized antler cancellous bone with various bioactive factors on their osteogenic potential

Biomaterials. 2013 Dec;34(36):9103-14. doi: 10.1016/j.biomaterials.2013.08.024. Epub 2013 Sep 3.

Abstract

Combinations of calcium phosphate scaffolds and bioactive factors are promising niche-mimetic solutions for repairing large-sized bone defects. However, the importance of compatibility between scaffolds and bioactive factors on their osteogenic outcomes has been largely ignored. This study aimed to investigate the compatibility of calcinated antler cancellous bone (CACB) scaffolds with various bioactive factors including icariin (ICA), velvet antler polypeptides (VAP) or recombinant human bone morphogenetic protein-2 (rhBMP-2) as well as their combinational osteogenic potential in vitro and in vivo. Scanning electron microscopy and fourier transform infrared spectroscopy confirmed the uniform distribution and chemical stability of the reagents on CABC. In vitro release profiles showed relative steady release of ICA from ICA/CACB, burst VAP release from VAP/CACB, and minimal rhBMP-2 release from rhBMP-2/CACB composites. When compared with VAP and rhBMP-2, incorporation of ICA within CACB resulted in most increased cell attachment, proliferation, alkaline phosphatase activity, osteogenic gene expression, and mineralization of rat bone marrow mesenchymal stem cells. In rabbit mandible critical-sized defects, the most extensive osteogenesis and neovascularization were observed in the ICA/CACB group. Differences between the VAP/CACB and rhBMP-2/CACB groups were not apparent. Interestingly, low pro-inflammatory (TNF-α, IL-6) and high anti-inflammatory (IL-10) mRNA levels were observed at scaffold implantation sites which were in close association with amount of new bone formation. These findings highlight that the compatibility between scaffolds and bioactive factors should been taken into account when considering the formula of optimized bone defect repair.

Keywords: Antler; Compatibility; Icariin; Osteogenic potential; VAP; rhBMP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Antlers / chemistry*
  • Biocompatible Materials / pharmacology*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone and Bones / chemistry*
  • Calcification, Physiologic / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Deer
  • Flavonoids / pharmacology
  • Humans
  • Male
  • Mandible / diagnostic imaging
  • Mandible / drug effects
  • Mandible / pathology
  • Materials Testing*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / ultrastructure
  • Osteogenesis / drug effects*
  • Peptides / pharmacology
  • Proteins / isolation & purification*
  • Rabbits
  • Rats
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • X-Ray Microtomography

Substances

  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Flavonoids
  • Peptides
  • Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Alkaline Phosphatase
  • icariin