Controlled decorin delivery from injectable microgels promotes scarless vocal fold repair

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.