Poly(glycerol carbonate) pressure sensitive adhesives for the in vivo closure of alveolar pleural fistulae

项目总结/摘要 该研究金将支持Danielle Fitzgerald女士在 波士顿大学的Mark Grinstaff博士和马萨诸塞州的Yolonda Colson博士共同赞助 综合医院/哈佛医学院。该建议的培训方面包括四个支柱： 跨学科研究，多学科指导，学术工程师-科学家培训，以及 专业发展。这种个性化的培训计划提供了一个独特的学习机会， 生物材料领域与关键的临床投入，并具体解决了她的职业目标，成为一名教授 在一所顶级大学里Grinstaff和Colson将继续定期与该研究员会面，作为她的一部分。 将提供必要的资源（空间、设备、用品、培训等）为她 成功 在研究方面，她的建议描述了一种新的可生物降解的，生物相容的压敏材料， 粘合剂（PSA），具有可调的粘合强度，用于体内使用。这项创新技术克服了 目前PSA的局限性，仅局部使用。与科尔森和格林斯塔夫博士一起， 肺泡胸膜瘘在胸外科中被认为是一种重要的和有问题的临床手术 与医疗保健费用增加和高死亡率有关。今天，关闭这种泄漏是 由于有限的空间和瘘管上固有的压力梯度而具有挑战性。具体来说，女士。 Fitzgerald正在评估新型聚（1，2-甘油碳酸酯）（PGCs），其功能类似于传统的聚碳酸酯。 聚丙烯酸酯PSA但具有可生物降解的碳酸酯键并降解成良性产物-例如， 甘油二氧化碳这些第一种聚合物提供了一个机会，创造一个新的一类PSA和转移 我们控制和处理胸内伤口的能力。拟议的实验将 测试这些基于PGC的压敏粘合剂将：1）在组成上表现出 依赖性粘合强度与较大的分子量、较长的烷基 链和立构规整性; 2）显示剥离强度，其可以在宽范围内调节， 便利贴®，具有类似Duct®胶带的性能;以及3）能够将胶原蛋白支撑物固定到外科手术器械上， 缝合器或电纺聚乳酸网状补片用于密封肺损伤。具体目标是：目标1。 合成并表征一系列PGC基压敏胶;目的2.评价 体外和体内PGC-粘附性胶原和PLA贴片的相容性;以及，目的3。评价 在猪模型中的PGC-粘附性胶原蛋白和PLA补片的性能。重要的是，初步数据 支持这些假设，并建立了良好的表征材料和严格的实验设计 在这项提案中，菲茨杰拉德女士的赞助商提供了必要的跨学科合作和专业知识， 包括共同顾问/共同导师和论文委员会成员。

Project Summary/Abstract This fellowship will support the interdisciplinary research and training of Ms. Danielle Fitzgerald under the co-sponsorship of Dr. Mark Grinstaff of Boston University and Dr. Yolonda Colson of the Massachusetts General Hospital/Harvard Medical School’s. The training aspects of the proposal include four pillars: interdisciplinary research, multi-disciplinary mentoring, academic engineer-scientist training, and professional development. This personalized training plan provides a unique opportunity for learning in the biomaterials area with critical clinical input, and specifically addresses her career goal of becoming a professor at a top-tier university. Drs. Grinstaff and Colson will continue to meet regularly with the fellow as part of her three-year plan and will provide the necessary resources (space, equipment, supplies, training, etc.) for her success. On the research front, her proposal describes new biodegradable, biocompatible pressure sensitive adhesives (PSAs), with tunable adhesion strength, for in vivo use. This innovative technology overcomes the limitation of current PSAs, which are only used topically. Together with Drs. Colson and Grinstaff, the repair of alveolar pleural fistulae was identified as a significant and problematic clinical procedure in thoracic surgery associated with increases in health care costs and high mortality rates. Today, closure of such leaks is challenging due to limited space and to an inherent pressure gradient across the fistula. Specifically, Ms. Fitzgerald is evaluating novel poly(1,2-glycerol carbonate)s (PGCs) which functionally mimic conventional polyacrylate PSAs but possess biodegradable carbonate linkages and degrade into benign products – e.g., glycerol, CO2. These first-of-their-kind polymers provide an opportunity to create a new class of PSAs and shift the paradigm around our ability to control and manage intrathoracic wounds. The proposed experiments will test the hypotheses that these PGC based pressure sensitive adhesives will: 1) exhibit compositionally dependent adhesive strength which positively correlates with greater molecular weight, longer alkyl chains, and stereoregularity; 2) display peel strengths which can be tuned over a wide range from Post-it® note to Duct® Tape like performance; and, 3) enable securing a collagen buttress to a surgical stapler or an electrospun polylactide mesh patch for sealing lung injuries. Her specific aims are: Aim 1. Synthesize and characterize a series of PGC-based pressure sensitive adhesives; Aim 2. Evaluate the compatibility of the PGC-adhesive collagen and PLA patch in vitro and in vivo; and, Aim 3. Evaluate the performance of the PGC-adhesive collagen and PLA patch in porcine models. Importantly, preliminary data support these hypotheses, and well-characterized materials and rigorous experimental designs are established in this proposal with essential cross-disciplinary collaborations and expertise from Ms. Fitzgerald’s Sponsors, co-advisors/co-mentors, and dissertation committee members included.