Covalently grafted VEGF(165) in hydrogel models upregulates the cellular pathways associated with angiogenesis

Area of Science:

• Biomedical Engineering
• Cell Biology
• Biomaterials Science

Background:

• Angiogenesis, the formation of new blood vessels, is crucial in physiological and pathophysiological processes.
• Vascular endothelial growth factor isoform 165 (VEGF(165)) drives endothelial cell proliferation, migration, and survival.
• Polyethylene glycol (PEG)-based hydrogels are being developed for in vitro angiogenesis, but molecular responses to incorporated VEGF(165) require further study.

Purpose of the Study:

• To investigate the molecular-level responses of endothelial cells to VEGF(165) within PEG hydrogels.
• To compare the effects of VEGF(165)-functionalized PEG hydrogels on human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC).

Main Methods:

• Human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC) were seeded on PEG hydrogels.
• Hydrogels were functionalized with grafted vascular endothelial growth factor isoform 165 (VEGF(165)) and Arg-Gly-Asp-Ser (RGDS) adhesion peptides.
• Upregulation of key intracellular proteins involved in angiogenesis was analyzed.

Main Results:

• Covalent incorporation of VEGF(165) into PEG hydrogels significantly upregulated key intracellular signaling proteins.
• These upregulated proteins are responsible for enhanced endothelial cell proliferation.
• The study observed increased endothelial cell migration and improved survival following apoptosis-inducing events.

Conclusions:

• PEG hydrogels functionalized with VEGF(165) effectively promote angiogenesis in vitro.
• The covalent grafting of VEGF(165) into PEG systems enhances endothelial cell responses crucial for blood vessel formation.
• This research provides insights into the molecular mechanisms underlying VEGF(165)-mediated angiogenesis in biomaterial systems.