Response of Human Umbilical Vein Endothelial Cells to Growth Factor Nanoparticles in Simulated Chronic Wound Environments

Chronic wounds are a type of persisting, non-healing wound, and have proven to be a difficult challenge to treat. These wounds are caused by factors such as restricted blood flow to the injury, repeated tissue damage, excessive inflammation and infection. An emerging research area involves the use of growth factors and other bioactive peptides to stimulate wound-healing mechanisms such as cell proliferation and migration. However, a suitable cell culture system that mimics the critical aspects of the chronic wound environment, which can be used to test potential therapeutics before they are tested in vivo, is lacking. Here, we develop a model for simulating chronic wounds in vitro using human umbilical vein endothelial cells (HUVECs) through a combination of low serum (1% fetal bovine serum), hypoxia (1% O[Formula: see text] and lipopolysaccharides (1-200 [Formula: see text]g/mL). We tested the proliferative and migratory responses of HUVECs to growth factor treatment under these chronic wound conditions individually, as well as in combination, to simulate the chronic wound environment. The growth factors used were fibroblast growth factor 2 (FGF-2) and FGF-2 fused elastin-like polypeptides (FGF-ELP). Fusion with ELP promotes self-assembly into nanoparticles, which imparts greater protection to proteolysis in the wound environment. It was found that HUVEC viability overall trended downwards across all groups of chronic wound conditions, suggesting the model effectively inhibited cell proliferation. When treated with FGF-ELP (25 nM), the proliferation response to the recombinant nanoparticles was significantly attenuated when comparing results between the chronic wound model and low serum baseline conditions. Despite the impaired level of proliferation in the simulated chronic wound environment, HUVECs responded positively to FGF-ELP, suggesting that FGF-ELP can promote a therapeutic effect even under chronic wound conditions. Using this chronic wound model, we can better simulate cell wound healing responses amidst several chronic wound conditions. To obtain a better understanding of the chronic wound system in vitro, there remains a need to investigate additional cell types and growth factor treatments that are active during the wound healing process.