Functional replication of the tendon tissue microenvironment by a bioimprinted substrate and the support of tenocytic differentiation of mesenchymal stem cells

Biomaterials. 2012 Nov;33(31):7686-98. doi: 10.1016/j.biomaterials.2012.07.002. Epub 2012 Jul 19.

Abstract

Although many studies have demonstrated that cell phenotype is affected by the surface properties of biomaterials, these materials often fail to mimic the complexity of the native tissue microenvironment (TME). In this study, we have developed a new experimental model that allows the characterisation and functional reconstruction of natural TME. We discovered that mesenchymal stem cells (MSC) cultured on cryostat sections of bovine Achilles tendon adopted an elongated and aligned morphology, and expressed tenocyte marker tenomodulin (TNMD). This suggests that tendon sections contain the signalling cues that guide MSCs to commit to the tenogenic lineage. To reconstruct this instructive niche, we prepared PDMS replica by using tendon sections as template. The resulting bioimprint faithfully copied the physical topography and elasticity of the section. This replica, when coated with collagen 1, supported tenogenesis of MSC without requiring exogenous growth factors. This study illustrates how extracellular biophysical and biochemical features intertwines to form a niche that influences the cell fate and demonstrated that such complex information could be conveniently reconstructed with synthetic materials and purified extracellular matrix proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology*
  • Cattle
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Lineage / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cellular Microenvironment / drug effects*
  • Cryoultramicrotomy
  • Dimethylpolysiloxanes / chemistry
  • Dogs
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / ultrastructure
  • Mice
  • Microscopy, Confocal
  • Models, Biological
  • Molecular Imprinting / methods*
  • Tendons / cytology*
  • Tendons / drug effects*
  • Water / chemistry

Substances

  • Biocompatible Materials
  • Dimethylpolysiloxanes
  • Membrane Proteins
  • Water
  • Green Fluorescent Proteins