Construction of a 3D bioprinted skin model for psoriasis research and drug evaluation.

Abstract

Psoriasis is a chronic inflammatory skin disease involving complex genetic, immune, and environmental interactions. Current<i>in vitro</i>models fail to fully replicate the human psoriatic microenvironment, while animal models are limited by species differences and ethical concerns, restricting their applicability in pathogenesis studies and drug screening. Here, we present a human-derived<i>in vitro</i>psoriasis model constructed via 3D bioprinting. By optimizing the bioink composition, we fabricated a full-thickness skin model with a vascularized dermal layer and a dense stratified epidermis. Cell viability in the bioprinted skin exceeded 90% after 7 d. The full-thickness skin exhibited a TEER value of ∼383 kΩ, reflecting native-like barrier integrity. Psoriatic features, including epidermal hyperplasia and upregulated inflammatory cytokines, were successfully induced through TNF-<i>α</i>and IL-22 stimulation. Structural and functional analyses confirmed that the model closely mimics the pathological hallmarks of psoriasis. Furthermore, drug testing showed that both tofacitinib and Danshensu effectively reduced IL-22 and TNF-<i>α</i>expression by more than 60%, while concurrently enhancing LOR expression by nearly 2-fold, reflecting improved epidermal differentiation. This study highlights the potential of 3D bioprinting in developing physiologically relevant skin disease models, providing a robust platform for psoriasis research and preclinical drug testing.