3D Printing of Skin Equivalents with Hair Follicle Structures and Epidermal-Papillary-Dermal Layers Using Gelatin/Hyaluronic Acid Hydrogels

Abstract

Recent advances in three-dimensional (3D) bioprinting technologies have enabled the fabrication of sophisticated live 3D tissue analogs. Despite the existing hydrogel-based bioinks, the development of advanced bioink materials that can accurately reproduce the composition of a native extracellular matrix and mimic the intrinsic properties of laden cells remains challenging. In this study, 3D printed skin equivalents incorporating hair follicle structures and epidermal/papillary dermal layers were fabricated using gelatin methacryloyl/hyaluronic acid methacryloyl (GelMA/HAMA) bioink. The composition of collagen and glycosaminoglycan in native skin was recapitulated by adjusting the combination of GelMA and HAMA. The GelMA/HAMA bioink exhibited excellent viscoelastic and physicochemical properties, 3D printability, cytocompatibility, and functionality to maintain hair-inductive potency while facilitating spontaneous hair pore development. The results indicate that GelMA/HAMA hydrogels are promising candidates as bioinks for the 3D printing of skin equivalents. Furthermore, they may serve as useful models for skin tissue engineering and regeneration.