Targeting the Glial Scar: Biomaterial and Drug‐Based Strategies for Modulation In Vitro

Glial scarring creates a significant obstacle for axonal regeneration in the central nervous system after injury and represents one of the main hurdles for neural microelectrode development. In this study, we established a test system for evaluating potential therapeutics and biomaterials prior to in vivo studies. The human cell line-based in vitro model replicates key glial scar characteristics such as galectin-3 expression and extracellular matrix accumulation. Moreover, we demonstrated how the model can be used to assess and validate new drug targets to reduce glial scar formation by modulating the transforming growth factor-β receptor types I and II. Beyond drug testing, our approach integrates a broad biomaterials science perspective, combining innovative chemical fabrication techniques with a complex in vitro co-stimulation system to investigate biological responses at the cell-material interface. To exemplify this, we explored the effects of sputter-coated free-standing nitinol as an exemplary implant material, along with gold and platinum electrode surfaces with varying characteristics, on glial scar-associated gene expression. By leveraging bioinspired material strategies, this platform enables the validation of promising drug candidates and their modes of action while optimizing neural implant materials to limit glial scar formation. Ultimately, this approach accelerates the development of strategies for central nervous system regeneration.