In vitro observations of self-assembled ECM-mimetic bioceramic nanoreservoir delivering rFN/CDH to modulate osteogenesis

Biomaterials. 2012 Oct;33(30):7468-77. doi: 10.1016/j.biomaterials.2012.06.095. Epub 2012 Jul 16.

Abstract

The cell-extracellular matrix (ECM) interaction has been employed to direct tissue-specific cellular responses and tailor biomaterial development. Given the important roles of integrin-fibronectin interactions and homophilic cadherin responses, we postulated that the recreation of the biological function of ECM in a recombinant fibronectin/cadherin chimera (rFN/CDH) at the nanoscale may properly address the integration impediment at the interface. This study aimed to investigate the feasibility and validity of an rFN/CDH bio-inspired ceramic surface generated via layer-by-layer (LbL) self-assembly to induce osteogenesis. The successful fabrication of a multilayered structure of BCP/LbL/[Chi-rFN/CDH] and excellent physico-chemical properties were confirmed by X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, contact angle, and scanning electron microscopy. Sustained release was observed during degradation, and the multilayered construct also displayed a significantly enhanced ability to guide bMSC adhesion, proliferation, and osteogenic differentiation. A mechanistic exploration revealed that the interaction of rFN/CDH with integrin α5β1/αvβ3 may be a regulatory pivot. These results demonstrate the hybrid potential of bioceramics coated with biofunctional rFN/CDH multilayers in osteoconductive and osteoinducive potency. This study therefore presents a basis for fabricating potential bio-functionalised ceramic-based substitutions for preclinical and clinical application to bone defects and reconstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetic Materials / pharmacology*
  • Cadherins / pharmacology
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Ceramics / pharmacology*
  • Drug Delivery Systems / methods*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Fibronectins / pharmacology
  • Gene Expression Profiling
  • Genetic Engineering
  • Integrins / metabolism
  • Ligands
  • Mesenchymal Stem Cells / cytology
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Photoelectron Spectroscopy
  • Protein Subunits / metabolism
  • Rabbits
  • Recombinant Proteins / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Surface Properties / drug effects

Substances

  • Cadherins
  • Fibronectins
  • Integrins
  • Ligands
  • Protein Subunits
  • Recombinant Proteins