Gelatin methacryloyl hydrogels functionalized with endothelin-1 for angiogenesis and full-thickness wound healing
Mengna Li, Hongping Yu, Qinfei Ke, Changqing Zhang, Youshui Gao, Yaping Guo
Abstract
Natural polymer hydrogels are widely used as wound dressings, but they do not have enough bioactivity to accelerate angiogenesis and re-epithelialization. Herein, a therapeutic system was firstly constructed in which endothelin-1 (ET-1), as an endogenous vasoconstrictor peptide, was embedded in a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel for full-thickness wound healing. The multifunctional GelMA-ET-1 hydrogels contained the arginine-glycine-aspartate (RGD) motifs of gelatin that provided adhesive sites for cell proliferation and migration. The ET-1 was wrapped within the network of crosslinked GelMA hydrogels via intermolecular hydrogen bonding interactions, effectively avoiding oxidization by atmospheric oxygen and in vivo enzymatic biodegradation. Notably, the ET-1 in the functional hydrogels significantly promoted the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The full-thickness skin defect model of rats further revealed that the GelMA-ET-1 hydrogels significantly accelerated new blood vessel formation, collagen deposition and re-epithelialization. After 14 days, the full-thickness skin defects almost closed and were filled with the newly formed tissue. Hence, the photo-crosslinking GelMA-ET-1 hydrogels functionalized with ET-1 can be employed as a promising therapeutic system for wound healing.