Loading of BMP-2-related peptide onto three-dimensional nano-hydroxyapatite scaffolds accelerates mineralization in critical-sized cranial bone defects

J Tissue Eng Regen Med. 2018 Apr;12(4):864-877. doi: 10.1002/term.2371. Epub 2017 Jul 28.

Abstract

Extrusion free-forming, as a rapid prototyping technique, is extensively applied in fabricating ceramic material in bone tissue engineering. To improve the osteoinductivity of nano-hydroxyapatite (nHA) scaffold fabricated by extrusion free-forming, in this study, we incorporated a new peptide (P28) and optimized the superficial microstructure after shaping by controlling the sintering temperature. P28, a novel bone morphogenic protein 2 (BMP-2)-related peptide, was designed in this study. Analysis of the structure, physicochemical properties and release kinetics of P28 from nHA sintered at temperatures ranging from 1000 °C to 1400 °C revealed that nHA sintered at 1000 °C had higher porosity, preferable pore size and better capacity to control P28 release than that sintered at other temperatures. Moreover, the nHA scaffold sintered at 1000 °C with P28 showed improved adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells compared with scaffolds lacking P28 or BMP-2. In vivo, nHA scaffolds sintered at 1000 °C with P28 or BMP-2 induced greater bone regeneration in critical-sized rat cranial defects at 6 and 12 weeks post-implantation compared with scaffolds lacking P28 or BMP-2. Thus, nHA scaffolds sintered at 1000 °C and loaded with P28 may be excellent biomaterials for bone tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: bone morphogenic protein 2-related peptide; bone regeneration; extrusion free-forming; nano-hydroxyapatite; repetitive acidic amino acid; sintering temperature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2* / chemistry
  • Bone Morphogenetic Protein 2* / pharmacology
  • Calcification, Physiologic / drug effects*
  • Cell Line
  • Durapatite* / chemistry
  • Durapatite* / pharmacology
  • Male
  • Mice
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Skull* / injuries
  • Skull* / metabolism
  • Skull* / pathology
  • Tissue Scaffolds / chemistry*

Substances

  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Peptides
  • Durapatite