Covalently immobilized VEGF-mimicking peptide with gelatin methacrylate enhances microvascularization of endothelial cells

Abstract

Clinically usable tissue-engineered constructs are currently limited due to their inability of forming microvascular networks necessary for adequate cellular oxygen and nutrient supply upon implantation. The aim of this study is to investigate the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). The construct was made of gelatin methacrylate (GelMA) based cell-laden hydrogel system, which was then covalently linked with VEGF-mimicking peptide (AcQK), using human umbilical vein endothelial cells (HUVECs) as the model cell. The results of the mechanics and gene expression analysis indicated significant changes in mechanical properties and upregulation of vascular-specific genes. The major finding of this study is that the increased expression of vascular-specific genes could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization. We conclude that GelMA with covalently-linked angiogenic peptide is a useful tissue engineered construct suitable for microvascularization. STATEMENT OF SIGNIFICANCE: (1) This study reports the conditions necessary for microvascularization in a tissue-engineered construct using vascular endothelial growth factor (VEGF). (2) The construct was made of gelatin methacrylate based cell-laden hydrogel system. (3) There is a significant change observed in mechanical properties and upregulation of vascular-specific genes, in particular CD34, when AcQK is used. (4) The major finding of this study is that the increased expression of vascular-specific genes, i.e., CD34 could be achieved by employing AcQK in the GelMA based hydrogel system, leading to accelerated microvascularization.

Keywords: Cell-laden hydrogels; Gelatin methacrylate; Human umbilical vein endothelial cells; Hydrogel; Microvascularization; Peptides.