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June 28th, 2025
Version: 1
University of Pennsylvania
bioengineering
biorxiv

Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair

Friedman, R.Open in Google Scholar•Brown, E. A.Open in Google Scholar•Bonelli, H. M.Open in Google Scholar•Gupta, Y.Open in Google Scholar•Aronson, M.Open in Google Scholar•McDaid, K.Open in Google Scholar•Oh, H. M.-Y.Open in Google Scholar•Bandora, E. A.Open in Google Scholar•Zur, K. B.Open in Google Scholar•Gottardi, R.Open in Google Scholar

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, alpha-smooth muscle actin (alpha-SMA) levels, and cell contractility. DCN was encapsulated in hyaluronic acid microgels for sustained protein release over 3 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.

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