Treatment of GERD Using Biodegradable Materials to Enhance Gastric Yield Pressure and GEJ Compliance Dynamics

项目摘要 胃食管反流病（GERD）影响全球8-33%的人口。GERD可导致食管炎、狭窄， 溃疡和Barrett食管（BE）。BE患者发生食管癌的风险增加125倍， 腺癌-一种毁灭性的结果，在大约80-90%的病例中是致命的。目前，黄金标准治疗 对于GERD，仍然使用长期质子泵抑制剂，即PPI治疗或腹腔镜Nissen胃底折叠术（LNF）。 然而，PPI治疗未能控制25%-42%的患者的GERD症状，并且PPI的长期使用与GERD症状相关。 会产生严重的副作用此外，委员会认为， LNF在技术上是严格的，目前只有不到1%的合格GERD 由于担心术后并发症和手术失败而寻求手术的人群。因此，替代的外科手术 需要进行治疗以缩小“治疗差距”。Re 最近，LINX磁性括约肌增强手术（MSA）已成为 一种替代手术选择，以解决治疗差距（FDA批准，2012年1月; Torax Medical，MN），The LINX 器械是一个永久性放置在胃食管连接处（GEJ）周围的磁铁环。虽然 MSA副作用特征略上级LNF，不幸的是， 术后吞咽困难发生率较高 常规 在LINX放置沿着后观察到器械侵蚀率较低。 为了解决这些问题并改善GERD治疗，我们开发了一种全新的GERD治疗方法： 可生物降解的装置。我们的设备被称为Eschara缝合领，由生物可吸收的致密管状基质组成， 在GEJ区域，在下食管括约肌周围形成胶原环的缝合材料。为 当材料在几天内生物降解时，它会失去拉伸强度，从而避免任何吞咽困难。短短几 在两周内，缝合环材料完全吸收，并通过异物反应留下胶原蛋白环， 提供适量的LES增强，以明显改善LES消退特征，增加 产生压力，降低GEJ处的顺应性，增加功能性LES长度，从而防止病理性酸 倒流我们开发了Eschara设备，以提供理想的GERD解决方案，具有以下优点， LNF和LINX：1）纠正GERD病理生理学，2）保留自然生理吞咽、打嗝和呕吐， 最大限度地减少吞咽困难，3）对迷走神经造成的风险最小，4）无侵蚀风险，5）MRI和所有成像，兼容， 6)制造简单，7）能够简化食管裂孔疝修补术，8）无需继续使用PPI。 为确保Eschara缝合领原型的充分性能，我们将1）制造并开发设计;然后2） 在活体猪模型中测试和验证它。根据初步实验结果，我们将：3）制作和开发 第二轮设计迭代; 4）进行第二次猪实验。第一阶段SBIR提案为我们准备了一个 SBIR第二阶段赠款旨在实现设计冻结，监管准备和商业化。此外，我们将批判地 评价我们的缝线模型，以确定Eschara技术是否能够有效满足GERD的需求 市场和成为一个成功的替代目前的手术技术，导致改善护理GERD患者。

PROJECT SUMMARY Gastroesophageal reflux disease (GERD) affects 8-33% of the global population. GERD can lead to esophagitis, strictures, ulcerations and Barrett's esophagus (BE). Patients with BE have up to an 125-fold increased risk of developing esophageal adenocarcinoma—a devastating outcome which is fatal in roughly 80-90% of cases. Currently, the gold standard treatment for GERD remains long-term proton pump inhibitors, i.e. PPI therapy, or laparoscopic Nissen fundoplication (LNF). However, PPI therapy fails to control GERD symptoms in 25%-42% of patients, and the chronic use of PPIs is associated with serious adverse effects. Moreover, LNF is technically exacting, and currently fewer than 1% of the eligible GERD population pursue surgery due to concerns of postoperative complications and surgical failure. Thus, an alternative surgical treatment is needed to close the “therapy gap”. Re cently, LINX magnetic sphincter augmentation surgery (MSA) has become an alternative surgical option to address the therapy gap (FDA-approved, January, 2012; Torax Medical, MN), The LINX device is a ring of magnets permanently placed laparoscopically around the gastroesophageal junction (GEJ). Although the side-effect profile of MSA is somewhat superior to LNF, unfortunately, high rates of postoperative dysphagia are routinely seen after LINX placement along with low rates of device erosion. To address these issues and improve GERD therapy, we have developed an entirely new class of GERD treatment: a novel biodegradable device. Our device is called the Eschara suture collar and consists of a dense, tubular matrix of bioabsorbable suture material that will create a ring of collagen around the lower esophageal sphincter, in the region of the GEJ. As the material biodegrades within a matter of days, it loses tensile strength, thus avoiding any dysphagia. Within a matter of weeks, the suture collar material totally absorbs and, via a foreign body reaction, leaves behind a collar of collagen that supplies the appropriate amount of LES augmentation to demonstrably improve LES effacement characteristics, increase yield pressure, decrease compliance at the GEJ, and increase functional LES length, thereby preventing pathologic acid reflux. We developed the Eschara device in order to provide an ideal GERD solution with the following advantages over LNF and LINX: 1) Correct GERD pathophysiology, 2) preserve natural physiological swallowing, belching, and vomiting, minimize dysphagia, 3) cause minimal risk to the vagus nerve, 4) no risk of erosion, 5) MRI, and all imaging, compatible, 6) simple manufacturing, 7) Enable simplified Hiatal Hernia repair, and 8) eliminate the need for continued PPI use. To ensure adequate performance of the Eschara suture collar prototype, we will 1) fabricate and develop the design; then 2) test and validate it in an in vivo swine model. Based on the results of initial experiments, we will: 3) Fabricate and develop the second round of design iteration; 4) perform second swine experiment. This Phase 1 SBIR proposal prepares us for an SBIR Phase II grant aimed at achieving design freeze, regulatory preparation, and commercialization. Also, we will critically evaluate our suture model to determine whether the Eschara technology could efficiently meet the needs of the GERD market and be a successful alternative to current surgical techniques, leading to improved care for GERD patients.