A Novel In Vitro Disease Model for Systemic Sclerosis Using Polyisocyanide Hydrogels

Systemic sclerosis (SSc) is a rare autoimmune disease with limited treatment options that is characterized by fibrosis in various organs. To screen the effectiveness of new therapies, there is an urgent need for reliable in vitro models. Key is that diseased cells' characteristics are maintained, which is challenging in currently used setups. In this study, an in vitro 3D culture system is described using the biocompatible polyisocyanide (PIC-RGD) hydrogel and SSc patient-derived fibroblasts from affected (lesional cells) and from healthy-skin (healthy cells). In contrast to the standard collagen-coated 2D cultures, the cells in the 3D PIC-RGD gels maintain the native phenotype and functionality of the primary cells. The functionality of the model is studied in the presence of the fibrosis stimulator transforming growth factor beta 1 (TGF beta 1) and the suppressor tumor necrosis factor (TNF alpha). In this study, it is observed that lesional cells have a stronger fibrotic character with increased contraction, proliferation, and expression of collagen, and myofibroblast markers alpha-smooth muscle actin and fibroblast activation protein. The high tunability of the hydrogel, which can maintain the native functionality of fibroblasts in in vitro cultures, delivers a crucial step in developing these materials into an effective tool for personalized medicine approaches of SSc patients.