Control of Angiogenesis and Host Response by Modulating the Cell Adhesion Properties of an Elastin-Like Recombinamer-based Hydrogel

Biomaterials. 2017 Aug;135:30-41. doi: 10.1016/j.biomaterials.2017.04.047. Epub 2017 Apr 28.

Abstract

The control of the in vivo vascularization of engineered tissue substitutes is essential in order to obtain either a rapid induction or a complete inhibition of the process (e.g. in muscles and hyaline-cartilage, respectively). Among the several polymers available, Elastin-Like Recombinamers (ELR)-based hydrogel stands out as a promising material for tissue engineering thanks to its viscoelastic properties, non-toxicity, and non-immunogenicity. In this study, we hypothesized that varying the cell adhesion properties of ELR-hydrogels could modulate the high angiogenic potential of adipose tissue-derived stromal vascular fraction (SVF) cells, predominantly composed of endothelial/mural and mesenchymal cells. Human SVF cells, embedded in RGD-REDV-bioactivated or unmodified ELR-hydrogels, were implanted in rat subcutaneous pockets either immediately or upon 5-day-culture in perfusion-bioreactors. Perfusion-based culture enhanced the endothelial cell cord-like-organization and the release of pro-angiogenic factors in functionalized constructs. While in vivo vascularization and host cell infiltration within the bioactivated gels were highly enhanced, the two processes were strongly inhibited in non-functionalized SVF-based hydrogels up to 28 days. ELR-based hydrogels showed a great potential to determine the successful integration of engineered substitutes thanks to their capacity to finely control the angiogenic/inflammation process at the recipient site, even in presence of SVF cells.

Keywords: Angiogenesis; Elastin-Like Recombinamers; Functionalization; Host reaction; Stromal vascular fraction.

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Culture Techniques
  • Elastin / chemistry*
  • Flow Cytometry
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • In Situ Hybridization
  • Male
  • Mesenchymal Stem Cells / cytology
  • Microscopy, Electron, Scanning
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Stromal Cells / cytology

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Elastin