Enhanced Vascular-like Network Formation of Encapsulated HUVECs and ADSCs Coculture in Growth Factors Conjugated GelMA Hydrogels

ACS Biomater Sci Eng. 2024 May 13;10(5):3306-3315. doi: 10.1021/acsbiomaterials.4c00465. Epub 2024 Apr 18.

Abstract

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.

Keywords: bFGF; gelMA; hADSCs; hUVECs; vEGF; vascular formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques*
  • Fibroblast Growth Factor 2* / metabolism
  • Fibroblast Growth Factor 2* / pharmacology
  • Gelatin* / chemistry
  • Gelatin* / pharmacology
  • Human Umbilical Vein Endothelial Cells*
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Methacrylates* / chemistry
  • Methacrylates* / pharmacology
  • Neovascularization, Physiologic / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tissue Engineering* / methods
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Hydrogels
  • Gelatin
  • Fibroblast Growth Factor 2
  • Vascular Endothelial Growth Factor A
  • Methacrylates
  • VEGFA protein, human
  • Intercellular Signaling Peptides and Proteins