Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair

Friedman, R.; Brown, E. A.; Bonelli, H. M.; Gupta, Y.; Aronson, M.; McDaid, K.; Oh, H. M.-Y.; Bandora, E. A.; Zur, K. B.; Gottardi, R.

doi:10.1101/2025.06.25.661429

bioRxiv · 10.1101/2025.06.25.661429

Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair

Friedman, R.·Brown, E. A.·Bonelli, H. M.·Gupta, Y.·Aronson, M.·McDaid, K.·Oh, H. M.-Y.·Bandora, E. A.·Zur, K. B.·Gottardi, R.

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Abstract

Vocal fold (VF) scarring is a leading cause of poor voice, yet no therapies exist to prevent its progression. Current treatments, such as intracordal steroid injections, offer limited efficacy and carry significant off-target toxicities. To identify targeted anti-scarring strategies, we performed transcriptomics of human VF myofibroblasts, the cellular drivers of VF scarring, and identified the proteoglycan decorin (DCN) as downregulated in activated myofibroblasts. We also show a time-dependent decrease in DCN during fibrotic wound healing in a preclinical rat model of VF scarring. Administration of DCN suppressed VF myofibroblast activation by reducing pro-fibrotic gene expression, -smooth muscle actin (-SMA) levels, and cell contractility. DCN was encapsulated in hyaluronic acid microgels for sustained protein release for 3-4 weeks. In a rat model of VF scarring, DCN-loaded microgels prevented hallmark features of scarring, including collagen deposition and myofibroblast activation. These findings highlight DCN as a promising therapeutic and provide a sustained delivery platform with translational potential against VF scarring. TeaserControlled decorin drug delivery from hyaluronic acid microgels attenuates myofibroblast activation to prevent vocal fold scarring, offering a translational strategy to improve post-injury voice outcomes.

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Friedman, R., Brown, E. A., Bonelli, H. M., Gupta, Y., Aronson, M., McDaid, K., Oh, H. M.-Y., Bandora, E. A., Zur, K. B., Gottardi, R.. 2025-06-28. Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair. https://doi.org/10.1101/2025.06.25.661429

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