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

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. A gelatin and hyaluronic acid‐based bioink was fabricated and triple‐layered skin tissue analogs were 3D printed. Compared to conventional 3D printed skin tissues, this study proposes novelties which are the presence of a papillary layer and hair follicle unit development. The papillary layer supports dermis‐epidermis interaction and induces spontaneous development of hair follicle units.