Advancements in in vitro psoriasis models: relevance for drug discovery and therapeutic development

Psoriasis is an incurable, autoimmune skin disorder manifested by abnormal keratinocyte differentiation and hyperproliferation, accompanied by immune cell infiltration within the epidermal layer. Clinically, it presents as erythematous, scaly plaques, and inflamed, dry skin on affected areas. The psoriasis pathogenesis is a complex characterized by an overactive immune system hyperproliferation of keratinocytes and neovascularization. This disease is a multifactorial etiology, involving environmental, genetic, and immune factors. In recent years, in vitro models have gained popularity for studying psoriasis due to their reproducibility and ability to mimic disease mechanisms accurately. The two-dimensional (2D) skin model is one of the in vitro cell culture models, which makes it easier to evaluate the inflammatory mediators. Advanced approaches involve a three-dimensional (3D) model that more closely mimics human skin physiology by replicating signaling pathways. A vascularised 3D skin model like a skin-on-chip incorporates microfluidic systems and dynamic perfusion. These models are valuable tools for the skin's functional and behavioral aspects. The available models are used in the early development stage and still require advancement in the future. This review provides an overview of psoriasis's key characteristics, examines various in vitro models for studying its pathophysiology, evaluates its efficacy, and discusses potential directions for future research.