Nebulized ECM Rescue Device (NERD) for Targeted Therapy in Vocal Fold Injuries.

Abstract

Extracellular matrix (ECM)-based scaffolds and gels demonstrate promise for vocal fold scar treatment; however, these injectables necessitate invasive procedures and repeated dosing. Multiple injections to the folds can damage the tissue, leading to fibrotic outcomes. We hypothesize that a nebulized vocal fold lamina propria ECM (VFLP-ECM) formulation can provide an effective regenerative treatment for upper airway delivery in a novel delivery approach. A porcine-derived, nebulized formulation of VFLP-ECM was synthesized for targeted VF delivery. Bilateral vocal fold injuries were induced in Sprague Dawley rats using micro forceps. Forty-eight hours postinjury, animals were assigned to a (1) injury alone/control group or a nebulized treatment group receiving (2) phosphate buffer saline (PBS), (3) collagen type I (COLI), or (4) extracellular matrix (VFLP-ECM), with six animals in each group. Larynges were harvested 14 days postinjury and histologically analyzed using Hematoxylin and Eosin and Masson's trichrome staining. Histological analysis demonstrated reduced collagen deposition and lower myofibroblast density in the VFLP-ECM treated group compared to PBS and injury alone controls. Additionally, treated tissues exhibited increased lamina propria thickness and improved extracellular matrix organization, indicative of regenerative rather than fibrotic remodeling. Nebulized delivery of VFLP-ECM improved VF tissue characteristics. This study suggests a potential application for nebulized decellularized ECM in supporting vocal fold tissue regeneration during the acute phase of wound healing, with long-term effects warranting further investigation. NA.