Soft Palate Modification Using a Collagen Crosslinking Reagent for Equine Dorsal Displacement of the Soft Palate and Other Upper Airway Breathing Disorders

Abstract

The mechanical properties of the soft palate can be associated with breathing abnormalities. Dorsal displacement of the soft palate (DDSP) is a naturally occurring equine soft palate disorder caused by displacement of the caudal edge of the soft palate. Snoring and a more serious, sometimes life-threatening, condition called obstructive sleep apnea (OSA) are forms of sleep-related breathing disorders in humans which may involve the soft palate. The goal of this study was to investigate the effect of injecting the protein crosslinker genipin into the soft palate to modify its mechanical properties for the treatment of equine DDSP with potential implications for the treatment of snoring and OSA in humans. Ex vivo experiments consisted of mechanical testing and a wind tunnel study to examine the effect of genipin on the mechanical properties, displacement, and vibration of equine soft palates. A pilot in vivo study was completed using DDSP and control horses to test the safety and effectiveness of injecting a genipin reagent into the soft palate. The wind tunnel testing demonstrated a greater than 50% decrease in transient deformation and a greater than 33% decrease in steady-state vibrations for all doses of genipin tested. Ultimate tensile stress, yield stress, and Young’s modulus were higher in the genipin-treated distal soft palate specimens by 52%, 53%, and 63%, respectively. The pilot in vivo study showed a reduction of snoring loudness in all DDSP horses and elimination of DDSP in at least one of three horses. The difficulty of using a 1-meter-long endoscopic injection needle contributed to a consistent overinjection of the equine soft palates, causing excessive stretching (pillowing) and related degradation of the tissue. These ex vivo and in vivo results demonstrated reduced vibration amplitude and flaccidity and increased strength of genipin-treated soft palates, suggesting that genipin crosslinking could become an effective and safe treatment for soft palate related breathing abnormalities.