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Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regeneration

Mui BW, Wong JJ, Dumas CE, Wang JH, Bray T, Hirose K, Connolly L, Winkel A, Timmler S, Bright NA, Sliauteryte E, Káradóttir RT, Robey PG, Franze K, Chalut KJ, Storer MA (2026)

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Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 392

Pages Range: eady3136-

Journal Issue: 6794

DOI: 10.1126/science.ady3136

Abstract

Tissue regeneration is rare in mammals, but the digit tip can regrow after amputation, whereas injuries beyond the nail do not. How the microenvironment drives divergent outcomes remains unclear. In this study, we found that the extracellular matrix (ECM) and tissue mechanics govern the amputation response in mouse digits. Nonregenerative regions were stiffer and contained dense, organized collagen, whereas regenerative regions were soft and enriched in hyaluronic acid (HA). Depleting HA inhibited regeneration and promoted fibrosis, demonstrating that the HA-collagen balance shaped tissue mechanics and repair signaling. Stabilization of HA with hyaluronan and proteoglycan link protein 1 (HAPLN1) after nonregenerative amputations tuned ECM mechanics, reduced scarring, and enhanced bone repair. Thus, ECM composition and mechanics influence cell behavior and ECM-targeted strategies could help unlock mammalian regeneration.

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How to cite

APA:

Mui, B.W., Wong, J.J., Dumas, C.E., Wang, J.H., Bray, T., Hirose, K.,... Storer, M.A. (2026). Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regeneration. Science, 392(6794), eady3136-. https://doi.org/10.1126/science.ady3136

MLA:

Mui, Byron W.H., et al. "Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regeneration." Science 392.6794 (2026): eady3136-.

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