A novel implantable device for a minimally invasive surgical treatment of obstructive sleep apnea: design and preclinical safety assessment

摘要

Background: In obstructive sleep apnea (OSA), occlusion of the upper airway by soft tissue causes intermittent hypoxemia and can have serious sequelae. A novel implantable medical device for OSA is composed of a linear silicone elastic element held in an extended state by a bioabsorbable external sheath. The implant is delivered to the tongue base or soft palate via a minimally invasive approach. Normal tissue healing anchors the device at the attachment points before the bioabsorbable material dissolves and the elastic element contracts to stabilize the surrounding tissue. Methods: Device prototypes were evaluated in multiple investigations: 1) a finite elements analysis model simulated the movement of the tongue base during sleep with and without the implant; 2) dynamic mechanical testing simulated 10?years’ normal use; 3) cadaveric implantations were conducted; 4) an ovine study in which implants of varying design were evaluated via gross pathology and histological assessment; and 5) a canine study in which implants of varying design in the tongue base and soft palate were evaluated via gross pathology and histological assessment. Results: 1) The implant was capable of reducing ~95% of tongue base movement during simulated sleep; 2) implants remained intact throughout the testing with no evidence of creep fatigue or change in dynamic modulus; 3) the device could be reliably deployed in the desired placement locations and was appropriate for various anatomies; and 4) all implants were well tolerated through 1?year, with minimal inflammatory responses. Conclusion: This new minimally invasive device for OSA has been demonstrated, through various bench and animal testing, to be safe, well tolerated, suitable for long-term use, and to function as intended. No adverse health consequences were observed in the animals, and histological evaluation indicated good healing. This study establishes proof of concept and supports human trials.