PGD: A Shape Memory Degradable Polymer for Transcather Atrial Sept

 描述（由申请人提供）：房间隔缺损（ASD）是最常见的先天性心脏病类型之一，如果不进行治疗，可能导致严重的心血管并发症。ASD通常可以通过经皮器械闭合成功治疗，但目前在美国可用的基于镍钛诺的ASD闭塞器械与罕见但严重的长期并发症相关，因为刚性金属框架在患者的剩余生命中保留在心脏中。我们建议开发一种新的形状记忆ASD封堵装置，其具有聚（十二烷酸甘油酯）（PGD）框架和小肠粘膜下（SIS）细胞外基质覆盖物，该材料具有生物相容性和完全生物降解性，可通过经导管输送系统输送，并可在ASD内展开，残留血液分流最少。生物可吸收器械将提供与现有器械相似的闭塞能力，但提供了允许支架在组织过度生长和完全闭合后被再吸收的额外受益。PGD材料将在拉伸机械性能和撕裂强度方面进行表征，并将组装原型器械。将在大型动物ASD模型中进行初步研究，以评估分流的短期和长期闭塞以及内皮化、心肌重塑和对植入材料的反应。最终，我们的目标是使用患者特定的尺寸创建可模制的PGD器械，提高器械放置成功的可能性，并增加适合经皮/经导管ASD闭合的患者数量。该项目的成功完成将为NIH R 01申请开发和测试PGD ASD封堵器的经导管输送系统奠定基础。

 DESCRIPTION (provided by applicant): Atrial Septal Defects (ASDs) are one of the most common types of congenital heart defects, and if left untreated can lead to severe cardiovascular complications. ASDs can often be successfully treated by percutaneous device closure, but the Nitinol-based ASD occlusion devices currently available in the U.S. are associated with infrequent, but significant long-term complications due to the stiff metal framework that remains in the heart for the remainder of the patient's life. We propose to develop a new shape memory ASD occlusion device with a poly(glycerol dodecanoate) (PGD) framework and small intestinal submucosal (SIS) extracellular matrix covering that is biocompatible and entirely biodegradable, can be delivered via a transcatheter delivery system, and can be deployed within an ASD with minimal residual shunting of blood. Bioresorbable devices will provide occlusion capabilities similar to current devices available, but offer the additional benefit of allowing the scaffolding to be resorbed once tissue overgrowth and complete closure has occurred. The PGD material will be characterized in terms of tensile mechanical properties and tearing strength, and prototype devices will be assembled. A pilot study will be performed in a large animal ASD model to assess short- and long-term occlusion of shunt flow, as well as endothelization, myocardial remodeling, and response to the implanted material. Ultimately, our goal is to create moldable PGD devices using patient-specific dimensions, improving the likelihood of successful device placement and increasing the number of patients eligible for percutaneous/transcatheter ASD closure. Successful completion of this project will form the basis for an NIH R01 application to develop and test a transcatheter delivery system for the PGD ASD occluders.