Author(s)
Sunjay Anekal, BS
Ananya Tadikonda, BS
Gabriel Sobczak, MD
Lena Chen, MD
Patrick Finnegan, BS
Stacey Halum, MD FACS
Affiliation(s)
Indiana University School of Medicine (IUSM); IUSM Department of Otolaryngology-Head and Neck Surgery;
Abstract:
Objective:
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a major cause of dysphonia. A placentally-derived connective tissue matrix (pd-CTM) has been shown to have a plethora of cytokines with potential therapeutic benefits in UVFP. This study aimed to identify and quantify the factors present in a commercially available pd-CTM (CTM Flow™, CTM Biomedical®, Lake Worth, Florida) and to study the effects of pd-CTM on the vocal fold microenvironment and function in mice with RLN injury.
Methods:
Various cytokines in pd-CTM were characterized using a cytokine array and ELISA. C57/BL6 mice were divided into 3 groups: uninjured negative controls (n=12), RLN transection with saline injection in the injured-side thyroarytenoid (TA) muscle (n=16), and RLN transection with pd-CTM injection in the injured-side TA muscle (n=16). Functional outcomes were assessed using laryngeal electromyography (L-EMG) testing and video laryngoscopy at 7- and 28-days post-operation. Animals were then euthanized, and larynges were harvested for immunohistochemistry (IHC) analysis and qPCR.
Results:
pd-CTM characterization showed moderate-to-high levels of neurotrophic (BDNF, CNTF, GDNF, NT-3), angiogenic (Angiogenin, VEGF-D), tissue remodeling (bFGF, IGF-1, HGF, TGFß-3), and anti-inflammatory (IL-1Ra) factors. Stimulated L-EMG demonstrated increased mean normalized area under the curve ratio in pd-CTM treated mice compared to saline treated mice at the 28-day time point indicating reinnervation (p < 0.001). IHC detected the presence of innervated neuromuscular junctions.
Conclusions:
pd-CTM may be a novel treatment option for patients with UVFP based on the neurotrophic, angiogenic, tissue remodeling, and anti-inflammatory factors present.