Crosslinkable Hydrogels for Tympanic Membrane Repair

用于鼓膜修复的可交联水凝胶

• 批准号: 6834234
• 负责人: GLENN DOWNES PRESTWICH
• 金额: $ 10万
• 依托单位: CARBYLAN BIOSURGERY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6834234
• 关键词: artificial membranes; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomechanics; biotechnology; chondroitin; crosslink; disease /disorder model; gel; guinea pigs; hearing; hearing tests; histology; hyaluronate; medical implant science; middle ear disorder; nonhuman therapy evaluation; ototoxin; regeneration; sulfates; tissue engineering; tympanoplasty; tympanum

DESCRIPTION (provided by applicant): Tympanic membrane perforation (TMP, or "ruptured eardrum") is a common occurrence caused by trauma, ear infections, or pressure equalization tube insertion. TMP may cause significant hearing loss or a portal for water exposure or infection. Current treatment uses a patient's own adipose or soft tissue to provide a template for repair of the perforation, often requiring general anesthesia and associated morbidity. The total cost of all TMP treatments approaches $60 million dollars annually. A substantial number of the patients with TMP are young children, and thus a convenient in-office protocol would be highly desirable. Sentrx Surgical, Inc. is a Utah startup company formed to commercialize in situ crosslinkable glycosaminoglycan (GAG) hydrogels for ear, nose and throat (ENT) and craniofacial surgery. Sentrx Surgical will establish the feasibility of using in situ crosslinkable hyaluronan (HA) and chondroitin sulfate (CS) hydrogels to improve outcome in repair of TMP. Preliminary data using an in vivo guinea pig model of acute TMP showed a significant increase in rate of TMP repair by simple injection of a gelling mixture of chemically-modified HA. In this Phase I STTR, Sentrx Surgical will partner with U Utah to establish the chemical and biological parameters that will demonstrate feasibility for using the in situ crosslinkable HA and CS hydrogels in human patients. Specifically, we will explore three specific aims: First, we will prepare four materials to select optimal mechanical and biological properties of the in situ crosslinkable gels. Second, we will establish the in vivo efficacy of each of the four materials for TMP repair in a guinea pig model. Third, we will evaluate the biocompability and otocompability of each gel in vivo by evaluating recovery of auditory function and middle ear histology.

描述（由申请人提供）：鼓膜穿孔（TMP，或“鼓膜破裂”）是由创伤、耳部感染或压力平衡管插入引起的常见事件。TMP可能导致严重的听力损失或水暴露或感染的门户。目前的治疗使用患者自身的脂肪或软组织来提供穿孔修复的模板，通常需要全身麻醉和相关的发病率。所有TMP治疗的总成本每年接近6000万美元。相当多的TMP患者是年幼的儿童，因此非常需要方便的办公室方案。 Sentrx Surgical，Inc.是一家犹他州的创业公司，旨在将用于耳鼻咽喉（ENT）和颅面手术的原位可交联糖胺聚糖（GAG）水凝胶商业化。Sentrx Surgical将确定使用原位可交联透明质酸（HA）和硫酸软骨素（CS）水凝胶改善TMP修复结局的可行性。使用急性TMP的体内豚鼠模型的初步数据显示，通过简单注射化学修饰的HA的凝胶化混合物，TMP修复率显著增加。在本I期STTR中，Sentrx Surgical将与U犹他州合作建立化学和生物学参数，以证明在人类患者中使用原位可交联HA和CS水凝胶的可行性。具体而言，我们将探索三个具体目标：首先，我们将准备四种材料，以选择最佳的机械和生物性能的原位交联凝胶。其次，我们将在豚鼠模型中确定四种材料中每一种用于TMP修复的体内功效。第三，我们将通过评价听觉功能和中耳组织学的恢复来评价每种凝胶的体内生物相容性和耳相容性。