Treatment of tracheal stenosis by drug eluting, bioabsorbable stent

药物洗脱生物可吸收支架治疗气管狭窄

• 批准号: 10319483
• 负责人: Mark Weidenbecher
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319483
• 关键词: Acute; Address; Affect; Anatomy; Animal Model; Animals; Anti-Inflammatory Agents; Antiinflammatory Effect; Autopsy; Biocompatible Materials; Biomechanics; Cadaver; Cell Adhesion; Cell Culture Techniques; Chemicals; Chronic; Cicatrix; Clinical; Clinical Data; Collagen; Data; Deposition; Devices; Dose; Effectiveness; Epithelial; Formulation; General Population; Generations; Glycolates; Healthcare; High Pressure Liquid Chromatography; Hospital Charges; Hybrids; In Situ; In Vitro; Incidence; Inflammation; Inflammatory; Inhalant dose form; Inhalation; Injury; Intubation; Measures; Methods; Monitor; Morbidity - disease rate; Mucous Membrane; Neck; Operative Surgical Procedures; Oryctolagus cuniculus; Patients; Perforation; Performance; Pharmaceutical Preparations; Phase; Population; Rehabilitation therapy; Respiratory Failure; Risk; Rotation; Secure; Silicones; Site; Soldier; Stenosis; Stents; Steroids; Structure; Techniques; Testing; Thick; Time; Tissues; Trachea; Tracheal Stenosis; Tracheostomy procedure; Trauma; Veterans; airway epithelium; airway obstruction; biodegradable polymer; biofabrication; biomaterial compatibility; clinical application; combat trauma; comorbidity; computerized; cost; density; design; experimental group; experimental study; healing; improved; improved outcome; in vivo; in vivo evaluation; innovation; macrophage; mechanical properties; migration; mortality; novel; novel therapeutics; patient population; polycaprolactone; pre-clinical; prevent; prototype; respiratory; restenosis; treatment group

Long-term intubation, tracheostomy, neck or inhalational trauma are common causes for subglottic and tracheal stenosis. Current surgical techniques may not correct the condition in all cases, resulting in restenosis and sometimes requiring a permanent tracheostomy. Tracheal stents can be used to address stenosis, but they have a number of potential shortcomings such as such as risk of acute airway obstruction, migration and poor biocompatibility. We have developed a novel drug-eluting stent concept to effectively eliminate such shortcomings. We hypothesize that a mometasone-eluting highly biocompatible multiphasic and spatially graded polycaprolactone-collagen (PCL-Col) stent that can treat tracheal stenosis effectively. Collagen phase at the lumen of the stent will facilitate full mucosalization whereas the macroporous PCL phase will biodegrade and release a steroid into the tracheal tissue to prevent re-stenosis. In Aim 1, the design of the self-deploying tracheal stent will be optimized. Geometric and compositional parameters of stent design will be varied to attain a stent, which expands and securely stays within the trachea after deployment to provide adequate tracheal wall support. Biomechanical tests will measure the strength of anchorage to avoid migration following stent expansion. Aim 2 will focus on optimizing the anti-inflammatory and epithelialization capacity of the stent: mometasone content will be systematically varied to study their anti-inflammatory effects using macrophage and airway epithelial cell cultures. High performance liquid chromatography will be used to quantify the release profile of mometasone over time. Aim 3 will focus on in vivo testing of the bioabsorbable, drug eluting stent: The effectiveness of stents will be tested in a rabbit animal model in which stenosis will be induced chemically. The following treatment groups will be included: (1) stenosis with no stent, (2) stenosis treated with a commercially available silicone stent, (3) stenosis treated with a PCL-collagen stent, (4) stenosis treated with a PCL-collagen-mometasone eluting stent. Stents will remain for 24 weeks in situ and longitudinally monitored for inflammatory changes, epithelialization, healing tendency, stent migration, and airway obstruction. At the completion of this project we will have obtained valuable pre-clinical data regarding optimum stent biomechanics and composition, which will prepare us for further long-term experiments in larger animals.

长期插管，气管造口术，颈部或吸入创伤是次听的常见原因和 气管狭窄。在所有情况下 再狭窄，有时需要永久​​性气管切开术。气管支架可用于解决 狭窄，但它们有许多潜在的缺点，例如急性气道的风险 阻塞，迁移和生物相容性差。我们已经开发了一种新颖的药物洗脱支架概念 有效消除这种缺点。我们假设一种莫莫替顿酮洗脱了 可以治疗可以治疗 气管狭窄有效。支架腔的胶原相将有助于全粘膜化 大孔PCL相会生物降解并将类固醇释放到气管组织中 防止重新发生。在AIM 1中，将优化自动驱动气管支架的设计。几何的 支架设计的组成参数将有所不同，以达到支架，该支架可以稳定扩展并牢固 部署后留在气管内，以提供足够的气管墙支撑。生物力学测试 将测量锚固的强度，以避免支架膨胀后迁移。 AIM 2将重点关注 优化支架的抗炎和上皮化能力：Mometasone含量将为 系统地使用巨噬细胞和气道上皮细胞研究其抗炎作用 文化。高性能液相色谱法将用于量化 随着时间的流逝。 AIM 3将重点放在生物吸收，药物洗脱支架的体内测试： 支架的有效性将在兔动物模型中进行测试，其中狭窄将被化学诱导。 将包括以下治疗组：（1）没有支架的狭窄，（2）用A 商业可用的硅胶支架，（3）用PCL-胶原蛋白支架处理的狭窄，（4）经过治疗的狭窄 带有PCL-Collagen次数驱动式支架。支架将保持原位和纵向24周 监测炎症变化，上皮化，愈合趋势，支架迁移和气道 梗阻。该项目完成后，我们将获得有关临床前数据的宝贵数据 最佳支架生物力学和组成，这将使我们为进一步的长期实验做好准备 较大的动物。