Collagen IV outperforms alternative ECM coatings to preserve human neural progenitor properties on electrically conductive neural interfaces.

Human neural progenitor cells (hNPCs) are promising candidates for neural repair, however, their in vitro expansion commonly relies on Matrigel, a tumor-derived and xenogeneic matrix that limits translational applicability. In this study, we evaluated defined extracellular matrix (ECM) coatings, including poly-L-ornithine (PLO), laminin, PLO/laminin, and collagen IV, as alternatives to Matrigel for hNPC culture under conventional and electrically stimulated conditions. We found that collagen IV consistently supported hNPC viability, proliferation, and maintenance of progenitor markers Nestin and SOX1 at levels comparable to Matrigel and superior to other chemically defined substrates. Enhanced ERK/MAPK signaling on collagen IV suggested integrin-mediated adhesion as a key mechanism underlying sustained cell survival. When applied to conductive indium tin oxide (ITO) neural interfaces, ECM coatings increased surface hydrophilicity without compromising electrical conductivity. Notably, collagen IV coated ITO maintained high hNPC viability and progenitor identity under uniform electrical stimulation. These findings identify collagen IV as a defined, electrically compatible ECM coating for conductive neural interfaces in translational neural engineering.