Biomimetic fractal topography enhances podocyte maturation in vitro

In their native environment, tissues are organized into intricate fractal structures, rarely recapitulated in their culture in vitro. The extent to which fractal (self-similar) patterns that resemble complex topography in vivo influence cell maturation remain inadequately elucidated. Yet, the application of fractal topographical stimulation may address the challenge of improving the differentiated cell phenotype in vitro. Here, we show fractality in the kidney glomerulus and podocytes, branching highly differentiated cells within the glomerulus. Biomimetic fractal patterns derived from glomerular histology are used to generate topographical (2.5-D) substrates for cell culture. Podocytes grown on fractal topography exhibit higher expression of functional markers and enhanced cell polarity. RNA sequencing suggests podocytes' enhanced ECM deposition and remodeling on fractal versus flat topography, and enhanced maturation accompanied by stress on fractal versus non-fractal topography. The incorporation of fractal topography into standard well plates may serve as a user-friendly bioengineered platform for high-fidelity cell culture.