A Composite Hydrogel Scaffold Permits Self‐Organization and Matrix Deposition by Cocultured Human Glomerular Cells

Three-dimensional scaffolds provide cells with a spatial environment that more closely resembles that of in vivo tissue, when compared to 2D culture on a plastic substrate. However, many scaffolding materials commonly used in tissue engineering tend to exhibit anisotropic morphologies that exhibit a narrow range of fibre diameters and pore-sizes, which do not recapitulate extracellular matrices. In this study, a fibrin hydrogel is formed within the interstitial spaces of an electrospun poly(glycolic) acid (PGA) monolith to generate a composite, bimodal scaffold for the co-culture of kidney glomerular cell lines. This new scaffold exhibits multiple fibre morphologies, containing both PGA microfibres (14.5 ± 2 µm) and fibrin gel nanofibres (0.14 ± 0.09 µm), which increase the compressive Young’s modulus beyond that of either of the constituents. The composite structure provides an enhanced 3D environment that increases proliferation and adhesion of immortalised human podocytes and glomerular endothelial cells. Moreover, the micro/nanoscale fibrous morphology promotes motility and reorganisation of the glomerular cells into glomerulus-like structures, resulting in the deposition of organised collagen IV; the primary component of the glomerular basement membrane (GBM).