On aligned fibrous substrates made from biodegradable PEUU, hCSSCs could be induced to secrete and organize a type-Ⅰ collagen-based ECM abundant in characteristic human corneal stromal ECM components. Spatial self-organization of the collagen-based ECM by hCSSCs featured stratified multilayered collagen-fibril lamellae with orthogonal orientation, and uniform fibril size and inter-fibril spacing in a pattern mimicking human corneal stromal tissue. In contrast, ECM secreted by hCF lacked comea-specific ECM components, leading to less-organized microstructure in a pattern akin to corneal scar-tissue. These observations demonstrate the potential for hCSSCs, under proper substrate and growth factor guidance, to facilitate the generation of a biological human cornea equivalent. In contrast hCFs were not similar responsive to these environmental cues and generated an ECM that poorly mimicked that native, functional tissue structure and composition.
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