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”)是一种常见的情况，由创伤、耳朵感染或插入压力均衡管引起。TMP可能会导致严重的听力损失或水暴露或感染的门户。目前的治疗方法使用患者自己的脂肪或软组织来提供修复穿孔的模板，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患者是幼儿，因此一个方便的办公室协议将是非常可取的。 Sentry x Surgical，Inc.是犹他州的一家初创公司，成立的目的是将用于耳鼻喉(ENT)和颅面手术的原位可交联性糖胺聚糖(GAG)水凝胶商业化。Sentrx Surgical将确定使用原位可交联性透明质酸(HA)和硫酸软骨素(CS)水凝胶来改善TMP修复效果的可行性。使用急性TMP豚鼠体内模型的初步数据显示，通过简单注射化学修饰的HA凝胶混合物，TMP修复率显著增加。在这一第一阶段的STTR中，Sentrx Surgical将与犹他州大学合作，建立化学和生物参数，以证明在人类患者中使用原位可交联性HA和CS水凝胶的可行性。具体地说，我们将探索三个具体目标：第一，我们将制备四种材料，以选择最佳的力学和生物性能的原位交联凝胶。其次，我们将在豚鼠模型上建立四种材料用于TMP修复的体内效果。第三，通过评价听功能恢复情况和中耳组织学检查，评价各凝胶在体内的生物相容性和耳相容性。