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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.
RESUMO
INTRODUCTION: Sucrose acetate isobutyrate (SAIB) is a water insoluble, biodegradable gel used for controlled-release oral and subcutaneous drug delivery. We investigated SAIB compatibility in the rat central nervous system (CNS) by implanting solutions of SAIB in adult and in neonatal brains. METHODS: 10-15 microL solutions of SAIB gels in 0-30% ethanol were injected into the cerebral cortex of adult Fischer 344 rats. Control animals were implanted with a 10 mg biodegradable poly anhydride copolymer of poly [bis (p-carboxyphenoxy) propane] anhydride and sebacic acid (PCPP:SA). Adult rats were evaluated for signs of pain and distress, including changes in posture, facial signs, and grooming behavior. 1-2 microL solutions of SAIB gels in 15% ethanol were injected into brains of 12-24 h-old rats. Neonatal rats were evaluated for survival. Adult and neonatal brains were examined by histopathology 3-48 days after implant. RESULTS: Gel implants produced elliptical compression of cortical tissue, cell loss, and inflammation. Cell loss appeared to be confined to the implantation wound and associated neuronal fields. In adult rats, neurophil compression, inflammation, and cell loss appeared similar with the 10-mg PCPP:SA implants and the 10-mg SAIB implants. There was no clinical evidence of pain or distress from SAIB implants. 1-2 microL implants of SAIB-15% ethanol had no effect on survival of neonatal animals. CONCLUSION: Brain implants of SAIB induce a mild to moderate inflammatory response and associated neuronal cell damage. The implants appeared to be biocompatible in adult and neonatal animals. These results suggest that further studies of SAIB as an injectable drug-delivery scaffold for CNS therapeutic agents are warranted.
