Current In Vitro Models of Oral Lichen Planus for Investigating Pathogenesis and Facilitating Drug Discovery: A Narrative Review.

BACKGROUND: Oral lichen planus (OLP) is highlighted as a chronic inflammatory disease of the oral cavity with an unclear etiopathogenesis. It is also categorized as an oral potentially malignant disorder. This disease is primarily driven by T-cell-mediated immune responses, leading to keratinocyte apoptosis and persistent inflammation. Despite the availability of therapeutic options, including corticosteroids and immunosuppressants, treatment remains challenging due to variable patient responses and disease chronicity. In vitro models play a crucial role in OLP research by mimicking the local inflammatory environment and providing insights into disease mechanisms and potential therapeutic strategies. While traditional two-dimensional (2D) cultures have contributed to the understanding of OLP pathogenesis, they lack the complexity needed to mimic the disease. Recent advancements in three-dimensional (3D) culture approaches, such as organotypic cultures, organ-on-a-chip devices, and microphysiological systems (MPS), offer enhanced physiological relevance by better mimicking immune-epithelial interactions and cytokine responses. However, no standardized in vitro model currently exists that fully recapitulates OLP's chronic inflammatory features and multifactorial pathology.

METHODS AND FINDINGS: This review addresses this critical gap by evaluating existing in vitro models, establishing validation criteria for developing reliable disease models, and identifying key challenges, including the absence of a fully functional immune system, lack of salivary immune components, and difficulties in maintaining stable long-term cultures. By synthesizing current evidence and limitations, we provide a framework for advancing bioengineered platforms and personalized medicine approaches to develop effective, patient-specific therapies for OLP.