Material context and TGF-β blockade timing determine retained matrix in patient-derived bioprinted keratoconus stroma
- 1Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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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BibTeX
@misc{jiang2026material,
title = {{Material context and TGF-β blockade timing determine retained matrix in patient-derived bioprinted keratoconus stroma}},
author = {H. Jiang and C. Zhou and F. Gao and Y. Pang and Y. Li and Y. Jie and H. Yang and Y. Jiang},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.764220},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.764220v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Material context and TGF-β blockade timing determine retained matrix in patient-derived bioprinted keratoconus stroma
AU - H. Jiang
AU - C. Zhou
AU - F. Gao
AU - Y. Pang
AU - Y. Li
AU - Y. Jie
AU - H. Yang
AU - Y. Jiang
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.764220
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.764220v1
AB - 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.
ER -