Characterization and development of a gelatin/elastin methacrylamide-based bioink for creating a 3D bioprinted human skin model

Abstract

Three-dimensional (3D) human skin constructs are gaining increasing relevance important in regenerative research, drug testing and the cosmetics industry. They offer great potential to overcome the anatomical and physiological limitations of animal models, yet current models are often limited by high costs, batch-to-batch variability, and mechanical properties that poorly replicate native skin. In particular, discrepancies in elasticity and tensile strength compared to the natural extracellular matrix (ECM) of skin remain a major challenge. To address this, we developed a novel hybrid hydrogel composed of 20% gelatin-methacrylamide (GelMA) and 5% methacrylated elastin (ElMA) derived from porcine aorta, forming the basis of a bi-layered 3D skin construct that mimics both epidermal and dermal ECM structures. Using this bioink, we created two distinct model variants: a GelMA-ElMA (GE) formulation and a GelMA-ElMA composition reinforced with a GelMA electrospun nanofleece (GEN) to support enhanced epidermal maturation. The resulting constructs support fibroblast proliferation within the dermal layer and epidermal stratification marked by expression of keratin 14, Keratin 10 and involucrin, reflecting the architecture of native skin. The presence of elastin contributed to high biocompatibility and cytocompatibility, enhancing both cell proliferation and metabolic activity. Furthermore, the model proved suitable for studying IL-1α-induced inflammation and wound healing processes. This work demonstrates the potential of GelMA-ElMA-based bioinks to advance skin tissue engineering by integrating mechanical stability with biological relevance, offering a promising platform for both fundamental research and applied testing.