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

项目摘要/摘要 这笔研究金将支持Danielle Fitzgerald女士在 共同赞助波士顿大学的Mark Grinstaff博士和马萨诸塞州的Yolonda Colson博士 综合医院/哈佛医学院。该提案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 职业发展。这一个性化的培训计划提供了一个独特的学习机会 生物材料领域有重要的临床投入，并明确提出了她成为一名教授的职业目标 在一所一流的大学。格林斯塔夫博士和科尔森博士将继续定期与这名男子会面，作为她的一部分。 三年计划，并将提供必要的资源(空间、设备、用品、培训等)为了她 成功。 在研究方面，她的提案描述了一种可生物降解、生物相容的压敏材料 粘合剂(PSA)，具有可调节的粘合强度，用于体内使用。这项创新技术克服了 限制目前仅在局部使用的PSA。与科尔森博士和格林斯塔夫博士一起，修复 肺泡胸膜瘘在胸部外科手术中被认为是一种重要且有问题的临床操作。 与卫生保健费用增加和高死亡率有关。今天，关闭这样的泄漏是 由于有限的空间和瘘管上固有的压力梯度，手术具有挑战性。具体地说，她说。 菲茨杰拉德正在评估一种新型的聚(1，2-甘油碳酸酯)S(PGCS)，它在功能上模拟传统的 聚丙烯酸酯PSA但具有可生物降解的碳酸酯连接并降解为良性产品--例如， 甘油，二氧化碳。这些首创的聚合物提供了创造一类新的PSA和转变的机会 围绕我们控制和处理胸腔内创伤的能力的范例。拟议中的实验将 测试这些PGC基压敏胶的假设：1)成分 依赖的粘合强度与较大的相对分子质量、较长的烷基呈正相关 链条和立体规整性；2)显示剥离强度，可以在很大范围内从 Post-it®Note to Duct®Tape；以及，3)能够将胶原蛋白支撑物固定到外科手术 缝合器或电纺聚乳酸网片用于封闭肺损伤。她的具体目标是：目标1。 合成并表征了一系列PGC基压敏胶；目的2.评价 PGC-粘附胶原蛋白与聚乳酸贴片的体内外相容性；目的3.评价 PGC-胶原胶和聚乳酸贴片在猪模型中的应用。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，菲茨杰拉德的赞助商进行了必要的跨学科合作和专业知识， 包括联合顾问/联合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.