Off-the-Shelf Patch for Repairing Tracheal Stenosis

 描述（由申请人提供）：本申请的长期目标是将气管补片推向市场，以治疗气管狭窄或气道狭窄，如果不治疗，这是一种危及生命的疾病，会影响幼儿和成人。目前，耳鼻喉科医生治疗气管狭窄只有两种主要选择。一个是一个复杂的外科手术，称为滑动气管成形术，在该国很少有外科医生真正有资格执行。另一种是将气管打开得更宽，并用肋软骨移植物保持其开放。两者都是困难的，耗时的程序与潜在的并发症。 我们已经提交了一项关于气管补片生物材料的美国专利申请，该材料克服了替代肋软骨移植所需的四个主要技术障碍：1）机械完整性，2）可缝合，3）可吸收，4）气密性。目前市场上还没有任何类似于气管狭窄合成贴片的想法。虽然学术组织工程界主要专注于用高度复杂的策略再生整个气管，可以说这导致了寻找应用的技术，但我们专注于识别特定患者的适应症，并设计了一种技术来填补这一空白。 共同研究者韦瑟利和Detamore已经合作了近十年，在对38只兔子进行初步研究并于2012年与Nanofiber Solutions合作后，作为一个团队，我们正处于一个转折点，需要进行大型动物研究才能将该技术转化为临床。因此，当前的I期SBIR项目高度集中于一个特定目标：证明工程气管补片修复绵羊气管诱导缺陷的概念验证（安全性）。我们将测试这样的假设，即用我们的工程气管补片覆盖诱导的气管缺损将使绵羊在气管狭窄最小的情况下存活。第一阶段项目的完成将使我们能够在战略上纳入FDA的指导，并在第二阶段SBIR中开始对绵羊进行全面的疗效研究，这将使我们能够进入临床。 与肋软骨相比 我们的气管补片具有以下优点：1）无需手术去除肋骨组织，节省手术室时间和成本，并消除肋骨部位的潜在并发症/感染和发病率（对患者和保险公司有吸引力），2）易于使用，因为它对进行肋软骨移植的外科医生来说是“即插即用”的（对外科医生有吸引力），3）不需要生物制剂或药物（对FDA批准的投资者有吸引力）。出于几个原因，我们把最初的临床翻译集中在喉气管狭窄的儿科人群。在 用最简单的话来说，我们的目标是为世界各地气道狭窄的儿童修复气管，帮助他们生存并恢复正常呼吸。

 DESCRIPTION (provided by applicant): The long term objective of this application is to bring a trachea patch to the market to treat tracheal stenosis, or narrowing of the airway, which left untreated is a life-threatening condition that affects both young children and adults. Currently, otolaryngologists have only two major options for treating tracheal stenosis. One is a complex surgical procedure known as slide tracheoplasty that few surgeons in the country are truly qualified to perform. The other is to open the trachea wider and hold it open with a graft of rib cartilage. Both are difficult, time- consuming procedures with potential complications. We have a U.S. patent application submitted on a trachea patch biomaterial that overcomes the four major technical hurdles required to replace rib cartilage grafting: 1) mechanical integrity, 2) suturable, 3) resorbable, and 4) air-tight. There is currently nothing on the market even remotely resembling the idea of a synthetic patch for tracheal stenosis. While the academic tissue engineering community has focused primarily on regenerating an entire trachea with highly complex strategies, arguably leading to technology in search of an application, we have focused instead on identifying a specific patient indication with an unmet need and designed a technology to fill that void. Co-investigators Weatherly and Detamore have worked together for nearly a decade, and after preliminary studies in 38 rabbits and partnering with Nanofiber Solutions in 2012, together as a team we are at an inflection point where a large animal study is necessary to translate the technology to the clinic. Therefore, the current Phase I SBIR project is highly focused with a single Specific Aim: To demonstrate proof of concept (safety) with engineered trachea patches to repair induced defects in sheep tracheas. We will test the hypothesis that covering induced trachea defects with our engineered trachea patches will allow sheep to survive with minimal tracheal stenosis. Completion of the Phase I project will strategically position us to incorporate FDA guidance and embark on a full-scale efficacy study in sheep in a Phase II SBIR that will allow us to proceed to the clinic. Compared to rib cartilage grafting, our trachea patch holds the following advantages: 1) No surgery to remove rib tissue, saving operating room time and cost, and eliminating potential complication/infection and morbidity at the rib site (attractive to patients and insurance companies), 2) Easy to use, as it i "plug and play" for surgeons who perform rib cartilage grafting (attractive to surgeons), 3) No biologics or drugs are required (attractive to investors for FDA approval). For several reasons, we focus initial clinical translation on the pediatric population with laryngotracheal stenosis. In the simplest terms, our goal is to fix tracheas for kids around the world with narrowed airways to help them survive and breathe normally again.