Development and validation of a cross-linked sodium hyaluronate based pig model for obstructive sleep apnea

Objective: This study aims to establish a novel, safe, and reversible animal model of obstructive sleep apnea (OSA) consistent with the pathophysiology of OSA and to investigate the relationship between upper airway obstruction and associated respiratory inflammatory responses. Methods: A novel technique involving precise multipoint injection of a cross-linked sodium hyaluronate mixture into the pharynx and palate of adult male Bama pigs via the oral cavity was employed to induce upper airway obstruction. Polysomnography (PSG) and computed tomography (CT) assessed the model's efficacy. Histopathology and enzyme-linked immunosorbent assay (ELISA) analyzed tissue responses and inflammatory markers. Results: PSG and CT confirmed upper airway obstruction and OSA events in the model pigs. Upper airway volume and cross-sectional area increased over time, reducing AHI events. The injected mixture showed gradual absorption and biosafety. Histopathological examination showed tissue response to OSA at different locations in the respiratory tract, including hyperkeratosis of the pharyngeal squamous epithelium and thickening of alveolar septa. Serum HIF-1α and IL-6 significantly increased 2 days post-injection. AHI correlated with upper airway minimum cross-sectional area, upper airway volume, HIF-1α, and TNF-α. Conclusion: A reversible, safe, and reliable pig model of OSA was successfully established, providing a robust platform for future OSA research and therapeutic exploration.