Phase II year
2019
(last award dollars: 2023)
Phase II Amount
$4,715,143
Chronic perforations of the tympanic membrane (TM) affect over 170,000 patients in the United States annually, often stemming from ventilation tubes inserted in the TM to drain fluid from middle ear infections. Left untreated, these TM perforations can lead to significant morbidities that include recurrent ear infection, conductive and sensorineural hearing loss, mastoid bone infection, and cholesteatoma development. Currently, TM perforations are repaired with a graft applied to the TM via an invasive surgery that can take 2-4 hours to complete, cost up to $18,000 per surgery, and carry significant anesthesia-related risks for pediatric patients. A nonsurgical alternative to the existing procedure that can reduce procedure time and morbidities would be of economic benefit to patients, otolaryngologists, and payors alike. We have developed a highly regenerative gel patch, called Perf-Fix, for nonsurgical TM repair. Perf-Fix can be applied to the TM through the ear canal without incisions or abrasion of the perforation margin, then cured via blue light into a stiff scaffold through which cells can migrate. The cells degrade the gel patch as they proliferate and migrate, resulting in total replacement of Perf-Fix with regenerated TM tissue. In this proposal, we aim to perform the necessary biocompatibility testing and applicator development ahead of FDA submission. We will evaluate Perf-Fix for safety in a series of biocompatibility tests, followed by a capstone animal trial to ensure that the final, sterilized form of Perf-Fix retains its regenerative capabilities. This will be followed by the development of an applicator for Perf-Fix that is suitable for human patients, and additional mechanical testing to ensure that Perf-Fix applied with the applicator retains the same properties seen in previous bench testing. The success of this proposal will allow Tympanogen to proceed with submission of Perf-Fix to the FDA, leading to a significant medical improvement over the current standard-of-care with a major reduction in healthcare costs.
Public Health Relevance Statement: NARRATIVE Chronic perforations of the tympanic membrane affect hundreds of thousands of patients, mostly children, each year and can lead to infection, hearing loss, nerve and brain damage. Currently, the only treatment for this condition is a costly, highly invasive surgery that can carry significant anesthesia-related risks for pediatric patients. We have developed a light-curable gel patch as a nonsurgical, office-based alternative for tympanic membrane repair that improves healing and eliminates surgical complications. This project proposes safety and efficacy testing to prepare the gel patch for submission to the FDA.
NIH Spending Category: Bioengineering; Brain Disorders; Hearing Loss; Infectious Diseases; Injury (total) Accidents/Adverse Effects; Neurosciences; Otitis Media; Patient Safety; Pediatric; Regenerative Medicine
Project Terms: Acute; Affect; Anesthesia procedures; Animals; Architecture; Autologous; base; biomaterial compatibility; Blast Injuries; Brain Injuries; Cadaver; Cartilage; Cells; Child; Chinchilla (genus); Cholesteatoma; Chronic; Cochlea; Consumption; cost; Data; design; Development; Devices; ear infection; Economics; efficacy testing; Elements; Engineering; Ensure; Environmental air flow; Evaluation; External auditory canal; Fascia; Feedback; Gel; healing; Health Care Costs; Hearing; hearing impairment; Hour; Human; human study; improved; In Vitro; in vivo evaluation; Infection; Lead; Left; Light; Liquid substance; Manufacturer Name; Mastoid process; Materials Testing; Mechanics; Medical; Medical Device; membrane model; Methods; Modeling; Morbidity - disease rate; Natural regeneration; Nerve; Operative Surgical Procedures; Osteomyelitis; Otitis Media; Otolaryngologist; ototoxicity; Outcome; Pathway interactions; Patients; pediatric patients; Perforation; Phase; Physicians; Physiology; Preparation; Procedures; Proliferating; Property; Protocols documentation; prototype; Publishing; Recurrence; regenerative; repaired; Reporting; Risk; Safety; safety testing; scaffold; Sensorineural Hearing Loss; Series; sound; standard of care; stem; Structure; success; Surgical complication; Surgical incisions; Temporal bone structure; Testing; Time; TimeLine; Tissue membrane; Transducers; Trauma; Tube; Tympanic membrane; Tympanic Membrane Perforation; United States; Work
