Gelatin methacryloyl hydrogels functionalized with endothelin-1 for angiogenesis and full-thickness wound healing

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 9; no. 23; pp. 47 - 479
• Main Authors: Li, Meng-Na, Yu, Hong-Ping, Ke, Qin-Fei, Zhang, Chang-Qing, Gao, You-Shui, Guo, Ya-Ping
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 16.06.2021
• Subjects: Angiogenesis; Biodegradation; Biological activity; Blood vessels; Cell migration; Cell proliferation; Collagen; Crosslinking; Endothelial cells; Endothelin 1; Fibroblasts; Gelatin; Gene expression; Glycine; Hydrogels; Hydrogen bonding; Medical dressings; Natural polymers; Polymers; Skin; Thickness; Umbilical vein; Wound healing
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb00449b

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. A therapeutic system was constructed first 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.