Organotypic artery-graft culture enables label-free multiphoton tracking of remodeling that links to long-term graft microarchitecture

Maestas, D. R.; Murphy, T.; Martinet, K. M.; Moyston, T.; Min, L. X.; Behrangzade, A.; Pemberton, B. J.; Ye, S.-H.; Hussey, G. S.; Azhar, M.; Wagner, W. R.; Vande Geest, J. P.

doi:10.64898/2026.02.28.708759

bioRxiv · 10.64898/2026.02.28.708759

Organotypic artery-graft culture enables label-free multiphoton tracking of remodeling that links to long-term graft microarchitecture

Maestas, D. R.·Murphy, T.·Martinet, K. M.·Moyston, T.·Min, L. X.·Behrangzade, A.·Pemberton, B. J.·Ye, S.-H.·Hussey, G. S.·Azhar, M.·Wagner, W. R.·Vande Geest, J. P.

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Abstract

The long-term performance of tissue-engineered scaffolds, particularly small-diameter vascular grafts, is shaped by remodeling events at the tissue-graft interface, yet these processes remain difficult to resolve longitudinally and at microstructural resolution in conventional implantation models. Here we develop an organotypic artery-graft model that preserves cylindrical vessel geometry and enables non-destructive label-free multiphoton monitoring of interface remodeling. Using second harmonic generation and two-photon excited fluorescence, we capture evolving fibrillar collagen architecture and cellularization over time, demonstrate compatibility with multiple biomaterial classes, and show integration with rat and mouse explants, live-cell dyes, and fluorescent reporter tissues. The platform resolved distinct remodeling responses to transforming growth factor-{beta} isoforms (TGF-{beta}1, -{beta}2, and -{beta}3), with differential shifts in collagen-fiber distributions, accompanied by changes in matrix-remodeling and contractile gene expression. Across two graft designs, culture-derived remodeling phenotypes, collagen fiber distributions, and initial trajectories agreed with those observed in long-term 6-month interpositional explants. Together, these results establish an accessible intermediate platform for interrogating artery-graft remodeling, tracking these trajectories, and prioritizing graft designs through interface-resolved outcomes before and alongside animal implantation studies.

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Maestas, D. R., Murphy, T., Martinet, K. M., Moyston, T., Min, L. X., Behrangzade, A., Pemberton, B. J., Ye, S.-H., Hussey, G. S., Azhar, M., Wagner, W. R., Vande Geest, J. P.. 2026-03-03. Organotypic artery-graft culture enables label-free multiphoton tracking of remodeling that links to long-term graft microarchitecture. https://doi.org/10.64898/2026.02.28.708759

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