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bioRxiv · 10.64898/2026.11.04.764220

Material context and TGF-β blockade timing determine retained matrix in patient-derived bioprinted keratoconus stroma

Jiang, H.·Zhou, C.·Gao, F.·Pang, Y.·Li, Y.·Jie, Y.·Yang, H.·Jiang, Y.
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Abstract

Stromal repair requires newly formed matrix to persist while the contractile response to TGF-{beta} is controlled. We developed patient-derived bioprinted gelatin methacryloyl (GelMA) stroma to connect material-dependent cell responses with matrix retention after timed receptor blockade. In constructs from six keratoconus (KC) and six normal donors, KC cells retained disease-associated transcription while secreting procollagen I and lumican at normal-donor levels per unit DNA. Comparisons with two-dimensional culture and matched cast GelMA showed that the three-dimensional environment increased matrix induction and lowered resting contractile expression. Printing added a stromal identity response that persisted as retained lumican. Delayed blockade after a TGF-{beta}1 pulse preserved matrix transcription and late secretion. Eleven days after withdrawal, this finite course left more native collagen and lower contractile-gene expression than vehicle in 9/12 donors. Across the tested blockade regimens, at least one regimen achieved both outcomes at the final endpoint in 11/12 donors, including every KC donor. Culture format changed the preferred regimen. Choosing finite blockade by retained collagen instead of secretion changed the schedule in half the donors; the selected arms contained 22.2% more collagen. Retained collagen and contractile expression therefore provide joint endpoints for designing when TGF-{beta}-pathway courses, including losartan and TGF-{beta}3 treatment for keratoconic and scarred corneas, should start and stop.

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Jiang, H., Zhou, C., Gao, F., Pang, Y., Li, Y., Jie, Y., Yang, H., Jiang, Y.. 2026-11-06. Material context and TGF-β blockade timing determine retained matrix in patient-derived bioprinted keratoconus stroma. https://doi.org/10.64898/2026.11.04.764220

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