Development of a 3D In Vitro Model of Dupuytren’s Disease as a Platform for Drug Screening

Abstract Background Dupuytren’s disease (DD) is a common fibrotic disorder of the hand, characterized by progressive thickening and contracture of the palmar and digital fascia. Surgical excision remains the primary treatment; however, there are currently no therapies to prevent disease progression or recurrence. This study aims to develop a 3D in vitro model to test novel antifibrotic therapies. The model is based on decellularized pathological DD tissue seeded with patient-derived fibroblasts, capturing the role of both cellular and extracellular matrix components in disease progression. Methods Fibrotic DD tissues were obtained from surgical excisions, sectioned, and decellularized. In parallel, primary fibroblasts were isolated from patient samples. The decellularized extracellular matrices (dECMs) were characterized with respect to biochemical composition, collagen structure, and mechanical properties. Fibroblasts were seeded onto the dECMs and cultured stepwise to initially promote proliferation, followed by differentiation into myofibroblasts. Secretomes of cells cultivated on the established 3D model were compared to those from conventional 2D cultivations. To evaluate the model´s relevance and effectiveness we tested the antifibrotic drug minoxidil. Results The dECMs retained the pathological architecture and mechanical properties of native DD tissue, although individual ECM components were reduced after decellularization. Fibroblasts successfully adhered, proliferated, and repopulated the scaffold. The relevance of the 3D model was demonstrated by the presence of myofibroblasts with disease–relevant secretome. The responsiveness to the drug minoxidil was significantly more complex in the 3D model than in conventional 2D cultures. Conclusion We demonstrated that dECM seeded with DD fibroblasts represents a relevant 3D in vitro model of Dupuytren’s disease. The model enables antifibrotic drug screening, as demonstrated by the testing of minoxidil. Our model provides a reproducible platform also suitable for the investigation of cells and ECM contributions to palmar fascial fibrosis.