The transparent outermost layer of the eye. Trauma, bacterial and viral infections, and heritable conditions lead to loss of corneal function and visual impairment in over ten million individuals world-wide. The limited supply of healthy cornea donor tissue has stimulated efforts to develop biological equivalents of human cornea. Corneal stroma comprises 90% of the corneal thickness and is the major structural component of the cornea characterized by layers of highly organized parallel collagen fibrils, mono-disperse in diameter with uniform interfibrillar spacing. The unique microstructure determines the robust biomechanical properties of this tissue and its optical transparency. Recapitulating the microstructure of native human corneal stromal tissue is believed to be a key feature in successfully engineering corneal tissue. Employing a strategy of surface contact guidance and growth factor supplementation, we demonstrate that on aligned fibrous substrates made from biodegradable poly(ester urethane) urea (PEUU), human corneal stromal stem cells (hCSSCs) could be induced by FGF-2 and TGF-β3 to secrete and organize a type-I collagen-based extracellular matrix (ECM) abundant in characteristic human corneal stromal ECM components, including keratan sulfate, lumican, and keratocan. 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.
The approach of combining substrate cues with growth factor augmentation offers a new means to engineer well-organized, collagen-based constructs with appropriate nanoscale structure for corneal repair and regeneration
INVESTIGATION OF Dr. Jian Wu
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