Abstract: The shortage of transplantable skin is the leading cause of death in patients with extensive skin defect. Addressing this challenge urgently requires the development of skin substitutes capable of wound repair and facilitating skin regeneration. In this study, a biomimetic bilayer skin tissue model consisting of collagen, gelatin/sodium alginate, fibroblasts, human umbilical vein endothelial cells, keratinocytes, melanocytes, and verteporfin was devised. Then, the skin model was fabricated using precise extrusion/inkjet bioprinters, and it reconstruction capabilities were evaluated through skin defect repair experiments. The printed skin tissue reduced the inflammatory response of the wound by 38% and inhibited the expression of TGF-β and YAP, and promoted the transformation of macrophages from M1 phenotype to M2 phenotype, thus promoting the reasonable reconstruction of fibronectin and collagen on the wound, finally promoting the wound healing, and reducing the wound contraction and scar formation. In addition, the proliferation and differentiation of human umbilical vein endothelial cells, keratinocytes, and melanocytes in printed skin increased the number of regenerated blood vessels by 123%, while promoting the reconstruction of multilayer epidermal structure and skin color. The outcomes of this investigation present a promising skin model and therapeutic strategy for skin injury, offering a potential avenue for the reconstruction of skin structure and function.

Key words: Bioprinting , · Multicellular printing , · Biomimetic , · Skin substitutes , · Wound healing