Nanostructured hydroxyapatite surfaces-mediated adsorption alters recognition of BMP receptor IA and bioactivity of bone morphogenetic protein-2

Acta Biomater. 2015 Nov:27:275-285. doi: 10.1016/j.actbio.2015.09.007. Epub 2015 Sep 7.

Abstract

Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal-coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass-uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sin<HAP<HAP-Pol. Furthermore, hybrid molecular dynamics and steered molecular dynamics simulations validated that BMP-2 tightly anchored on the HAP-Pol surface with a relative loosened conformation, but the HAP-Sin surface induced a compact conformation of BMP-2. In conclusion, the nanostructured HAPs can modulate the way of adsorption of rhBMP-2, and thus the recognition of BMPR-IA and the bioactivity of rhBMP-2. These findings can provide insightful suggestions for the future design and fabrication of rhBMP-2-based scaffolds/implants.

Statement of significance: This study provides strong evidences that nanoscaled HAPs yield extraordinary influence on the adsorption behaviors and bioactivity of rhBMP-2. It has been found that the surface roughness and crystallinity played a crucial role in governing the way of rhBMP-2 binding to HAPs, and thus the conformation, recognition of BMPR-IA and bioactivity of adsorbed rhBMP-2. It is also for the first time to correlate numerical modeling and experimental results of the bioactivity of rhBMP-2 on nanostructured HAPs. This work can pave an avenue for the wider uses of rhBMP-2 in clinical applications and arouse broad interests among researchers in the fields of nano-biotechnology, biomaterials and bone tissue engineering.

Keywords: Adsorption; BMP-2; Bioactivity; Hydroxyapatite; Molecular dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Binding Sites
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Morphogenetic Protein 2 / chemistry*
  • Bone Morphogenetic Protein Receptors, Type I / chemistry*
  • Coated Materials, Biocompatible / chemical synthesis*
  • Diffusion
  • Durapatite / chemistry*
  • Materials Testing
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Particle Size
  • Protein Binding
  • Surface Properties

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Coated Materials, Biocompatible
  • Nanocapsules
  • Durapatite
  • Bone Morphogenetic Protein Receptors, Type I