3-Dimensional spatially organized PEG-based hydrogels for an aortic valve co-culture model

Biomaterials. 2015 Oct:67:354-64. doi: 10.1016/j.biomaterials.2015.07.039. Epub 2015 Jul 21.

Abstract

Physiologically relevant in vitro models are needed to study disease progression and to develop and screen potential therapeutic interventions for disease. Heart valve disease, in particular, has no early intervention or non-invasive treatment because there is a lack of understanding the cellular mechanisms which lead to disease. Here, we establish a novel, customizable synthetic hydrogel platform that can be used to study cell-cell interactions and the factors which contribute to valve disease. Spatially localized cell adhesive ligands bound in the scaffold promote cell growth and organization of valve interstitial cells and valve endothelial cells in 3D co-culture. Both cell types maintained phenotypes, homeostatic functions, and produced zonally localized extracellular matrix. This model extends the capabilities of in vitro research by providing a platform to perform direct contact co-culture with cells in their physiologically relevant spatial arrangement.

Keywords: Biomimetic material; Co-culture; Endothelialisation; Heart valve; Hydrogel; Scaffold.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Animals
  • Aortic Valve / cytology*
  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Cell Adhesion / drug effects
  • Coculture Techniques / methods*
  • Endothelial Cells / cytology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Hydrogels / chemistry*
  • Models, Biological*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Peptides / pharmacology
  • Phenotype
  • Platelet Adhesiveness / drug effects
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polyethylene Glycols / chemistry*
  • Sus scrofa
  • Time Factors
  • Tissue Scaffolds / chemistry

Substances

  • Hydrogels
  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Nitric Oxide
  • Polyethylene Glycols
  • Nitric Oxide Synthase Type III