3D Organotypic Skin Models Recapitulate Autoantibody-Driven Pemphigus Pathomechanisms and Targeted Therapeutic Response

The study introduces a 3D organotypic skin model that effectively mimics the pathomechanisms of pemphigus vulgaris (PV), an autoimmune blistering disorder, and evaluates targeted therapeutic responses. By using 3D bioprinting and cell self-organization, the model replicates the disruption of the epidermal barrier by pathogenic antibodies and allows for the study of disease phenotypes and therapeutic responses. It incorporates a vascularized dermal matrix, enabling physiological dissemination of autoantibodies and demonstrating the critical role of the dermal microenvironment in disease modeling and drug response. The study tested three EGFR-targeted tyrosine kinase inhibitors, with osimertinib and lapatinib showing the most efficacy in stabilizing cell junctions. Additionally, a machine learning-assisted approach was introduced for high-throughput therapeutic screening, enhancing the model's utility in drug testing. This advanced skin model offers a robust platform for studying PV and testing potential treatments, overcoming limitations of previous models by incorporating vascularized and stratified tissue structures.