Abstract: BACKGROUND: Tissue engineering technology holds broad application prospects in the repair and treatment of tissues and organs, offering a novel solution for the treatment of large-scale skin defects. However, due to the complexity of skin structure, constructing functional three-dimensional skin tissue engineering models to mimic or replace natural skin remains challenging.
OBJECTIVE: To develop a bio-mimetic methyl acrylated hyaluronic acid/decellularized skin hydrogel scaffold and evaluate its effects on the proliferation, activity, migration and tube formation of human umbilical vein endothelial cells. 
METHODS: Digital light processing 3D printing technology was utilized to produce methyl acrylated hyaluronic acid hydrogel scaffolds and methyl acrylated hyaluronic acid/decellularized skin matrix hydrogel scaffolds. The microscopic morphology of the two scaffolds was observed under a scanning electron microscope. The effects of the two scaffolds on the migration of human umbilical vein endothelial cells were detected by Tranwell chamber and scratch test. The effect of the two scaffolds on the tube formation of human umbilical vein endothelial cells was detected by the tube formation experiment. The human umbilical vein endothelial cells were resuspended in the precursor solution of the two scaffolds. The methyl acrylated hyaluronic acid hydrogel scaffold containing human umbilical vein endothelial cells and the methyl acrylated hyaluronic acid/decellularized skin matrix hydrogel scaffold were prepared by digital light processing 3D printing technology. The proliferation, activity, and state of human umbilical vein endothelial cells in the two scaffolds were detected by CCK-8 assay, live/dead staining, and phalloidin staining.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that both scaffolds presented a three-dimensional porous structure with interconnected pores; both scaffolds could promote the migration and tube formation of human umbilical vein endothelial cells, and the promoting effect of methyl acrylated hyaluronic acid/decellularized skin matrix hydrogel scaffold was stronger than that of methyl acrylated hyaluronic acid hydrogel scaffold. (2) CCK-8 assay results showed that both scaffolds could promote the proliferation of human umbilical vein endothelial cells, and the proliferation of cells in methyl acrylated hyaluronic acid/decellularized skin matrix hydrogel scaffold was faster. Live/dead staining showed that the human umbilical vein endothelial cells in both hydrogel scaffolds were uniformly and three-dimensionally distributed, and both had a high survival rate. Phalloidin staining showed that the human umbilical vein endothelial cells in both scaffolds showed a good extension state and the cells in the methyl acrylated hyaluronic acid/decellularized skin matrix hydrogel scaffold were more fully extended. (3) The results showed that the methyl acrylated hyaluronic acid/decellularized skin hydrogel scaffold could promote the proliferation, migration, and tube formation of human umbilical vein endothelial cells and had good cell compatibility.

Key words: digital light processing">, 3D printing">, skin tissue engineering">, skin regeneration">, decellularized skin matrix">, cell proliferation">, cell migration, cell tube formation">, engineered skin