Conductive Polyisocyanide Hydrogels Inhibit Fibrosis and Promote Myogenesis.

Reliable in vitro models closely resembling native tissue are urgently needed for disease modeling and drug screening applications. Recently, conductive biomaterials have received increasing attention in the development of in vitro models as they permit exogenous electrical signals to guide cells toward a desired cellular response. Interestingly, they have demonstrated that they promote cellular proliferation and adhesion even without external electrical stimulation. This paper describes the development of a conductive, fully synthetic hydrogel based on hybrids of the peptide-modified polyisocyanide (PIC-RGD) and the relatively conductive poly(aniline-co-N-(4-sulfophenyl)aniline) (PASA) and its suitability as the in vitro matrix. We demonstrate that incorporating PASA enhances the PIC-RGD hydrogel's electroactive nature without significantly altering the fibrous architecture and nonlinear mechanics of the PIC-RGD network. The biocompatibility of our model was assessed through phenotyping cultured human foreskin fibroblasts (HFF) and murine C2C12 myoblasts. Immunofluorescence analysis revealed that PIC-PASA hydrogels inhibit the fibrotic behavior of HFFs while promoting myogenesis in C2C12 cells without electrical stimulation. The composite PIC-PASA hydrogel can actively change the cell fate of different cell types, providing an attractive tool to improve skin and muscle repair.

An Improved Understanding of the Pathophysiology of Pelvic Organ Prolapse: A 3D In Vitro Model under Static and Mechanical Loading Conditions.

The suboptimal outcomes of pelvic organ prolapse (POP) surgery illustrate the demand for improved therapies. However, their development is hampered by the limited knowledge on the cellular pathophysiology of POP. Current investigations, that are limited to tissues and 2D in vitro models, provide highly inconclusive results on how the extracellular matrix (ECM) metabolism and fibroblasts are affected in POP. This study uses a physiologically relevant 3D in vitro model to investigate the cellular pathophysiology of POP by determining the differences between POP and non-POP fibroblasts on ECM metabolism, proliferation, and fibroblast-to-myofibroblast (FMT) transition. This model, based on the synthetic and biomimetic polyisocyanide hydrogel, enables the incorporation of mechanical loading, which simulates the forces exerted on the pelvic floor. Under static conditions, 3D cultured POP fibroblasts are less proliferative, undergo FMT, and exhibit lower collagen and elastin contents compared to non-POP fibroblasts. However, under mechanical loading, the differences between POP and non-POP fibroblasts are less pronounced. This study contributes to the development of more comprehensive models that can accurately mimic the POP pathophysiology, which will aid in an enhanced understanding and may contribute to improved therapies in the future.