3D printing of a thermosensitive hydrogel for skin tissue engineering: A proof of concept study

Because of important functions of skin, an effective therapy is demanded for serious full-thickness skin injuries. In this study, a thermosensitive poly (N-isopropylacrylamide-co-acrylic acid) (p(NIPAAm-AA) hydrogel was prepared and successfully used for different 3D printing methods, including 3D printing with a single needle nozzle and a single syringe (3D single nozzle extrusion printing), 3D printing with coaxial needles and double syringes (3D coaxial printing), and 3D printing with a single needle nozzle and double syringes (3D hybrid printing). It was found that a relatively high cell viability of keratinocytes, fibroblasts and endothelial cells was achieved when 3D hybrid printing of the hybrid bioink (p(NIPAAm-AA) and fibrin) with cells and the cell viability was independent of cell type, seeding density, printed position and cultivation time. These skin-related cells in the hybrid bioink were printed into a biocompatible porous supporting polyvinyl alcohol (PVA) scaffold with customized patterns and thicknesses and terminal differentiation of these cells were induced by air-liquid-interface (ALI) culture in vitro. Superficial cornification of the epidermis layer as well as sprouting and splitting of the subcutaneous endothelial cells were evidenced by histology and immunofluorescence imaging. The bioengineered skin constructs might be used as potential implants for effective wound healing.