Surface immobilization of MEPE peptide onto HA/β-TCP ceramic particles enhances bone regeneration and remodeling

J Biomed Mater Res B Appl Biomater. 2012 Apr;100(3):841-9. doi: 10.1002/jbm.b.32648. Epub 2012 Jan 25.

Abstract

Calcium phosphate ceramics have been widely used as scaffolds for bone regeneration. Here, to improve the osteogenic potential of hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) and to apply the bioactive peptide in situ, matrix extracellular phosphoglycoprotein (MEPE) peptide, which has been shown to stimulate osteoblast differentiation, was covalently and directionally immobilized on HA/β-TCP particles. The free-hydroxyl groups on the surface of the HA/β-TCP particles were sequentially conjugated with APTES, PEG-(SS)(2), and the synthetic MEPE peptide. Using FTIR and XPS, immobilization of the MEPE peptide on the HA/β-TCP was confirmed. Implantation of the MEPE peptide-immobilized HA/β-TCP into calvarial defect and subsequent analyses using a micro CT and histology showed significant bone regeneration and increased bone area (9.89-fold) as compared to that of unmodified HA/β-TCP. Moreover, tartrate-resistant acid phosphatase-positive osteoclasts were observed in regenerated bone by the MEPE peptide-immobilized HA/β-TCP, indicating that the bones newly formed by the MEPE peptide-immobilized HA/β-TCP are actively remodeled by osteoclasts. Therefore, our data demonstrate that MEPE peptide immobilization onto the HA/β-TCP surface stimulates bone regeneration associated with physiological bone remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Calcium Phosphates* / chemistry
  • Calcium Phosphates* / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Durapatite* / chemistry
  • Durapatite* / pharmacology
  • Extracellular Matrix Proteins* / chemistry
  • Extracellular Matrix Proteins* / pharmacology
  • Glycoproteins* / chemistry
  • Glycoproteins* / pharmacology
  • Humans
  • Immobilized Proteins* / chemistry
  • Immobilized Proteins* / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Phosphoproteins* / chemistry
  • Phosphoproteins* / pharmacology
  • Skull Fractures / metabolism
  • Skull Fractures / pathology
  • Skull Fractures / therapy*

Substances

  • Calcium Phosphates
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Immobilized Proteins
  • MEPE protein, human
  • Peptides
  • Phosphoproteins
  • beta-tricalcium phosphate
  • Durapatite