Bioactive micropatterning of biomaterials for induction of endothelial progenitor cell differentiation: Acceleration of in situ endothelialization

J Biomed Mater Res A. 2020 May;108(7):1479-1492. doi: 10.1002/jbm.a.36918. Epub 2020 Apr 16.

Abstract

Synthetic grafts do not provide an appealing surface for endothelial cells to adhere and colonize the inner surface. To promote in situ endothelialization the following aspect has to be taken into account, endothelial progenitor cells (EPCs) needs to be mobilized on the surface of the graft. The surface of the graft has to be sufficiently biocompatible to create a prone environment for the EPCs to adhere, proliferate and, differentiate to form a layer and subsequently improve graft patency. In this work, two active molecules GRGDS and sitagliptin, were chosen for their abilities to recruit, enhance adhesion and induce differentiation of endothelial progenitor cells. They were grafted on PET surfaces in order to provide restrained cues triggering cell alignment and evaluate the influence of such structuration on EPCs fate. We then analyze cell behavior onto functionalized biomaterials. Their abilities to control EPCs fate were demonstrated via RT-qPCR, immunofluorescence, and enzymatic tests. The GRGDS/sitagliptin 100 × 10 surface enables to reduce the stemness phenotype on EPCs and induce the expression of endothelial lineage markers. These results highlight the importance of spatial patterning cues in guiding EPCs organization and function, which may have clinical relevance in the development of vascular grafts that promote patency.

Keywords: endothelial progenitor cells; endothelialization; in situ differentiation; peptides grafting; surface functionalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Endothelial Progenitor Cells / cytology*
  • Endothelial Progenitor Cells / drug effects
  • Humans
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Sitagliptin Phosphate / chemistry
  • Sitagliptin Phosphate / pharmacology*
  • Surface Properties

Substances

  • Biocompatible Materials
  • Oligopeptides
  • glycyl-arginyl-glycyl-aspartyl-serine
  • Sitagliptin Phosphate