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

用于体内闭合肺泡胸膜瘘的聚（甘油碳酸酯）压敏粘合剂

基本信息

批准号：
10463117
负责人：
Danielle Fitzgerald
金额：
$ 4.68万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2025-11-15
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10463117
关键词：
Abraxane Acrylates Address Adhesions Adhesives Air Air Movements Alcohols Alveolar Area Bacterial Infections Bandage Behavior Benign Biocompatible Materials Boston Carbon Dioxide Carbonates Carboxylic Acids Cell Communication Chemical Structure Chemistry Chest Clinic Clinical Collaborations Collagen Committee Members Communication Complex Data Development Development Plans Duct (organ) structure Engineering Enrollment Epithelial Equipment and Supplies Evaluation Excision Exhibits Experimental Designs Family suidae Fellowship Fibroblasts Fistula Formulation General Hospitals Glass Glyceric Acids Glycerol Goals Health Care Costs Human Hydrophobicity In Vitro Individual Infection Injury Interdisciplinary Study Learning Libraries Liquid substance Lung Massachusetts Medical Mentors Modeling Molecular Weight Morbidity - disease rate Mus Oligonucleotides Operative Surgical Procedures Oral Organ Performance Physicians Pleural Pleural cavity Polymers Prevention Procedures Property Research Research Project Grants Research Training Resources Respiration Respiratory physiology Scientist Secure Series Structure Structure of parenchyma of lung Surgical Staplers Techniques Testing Thoracic Surgical Procedures Tissue Engineering Tissues Training Training Programs Translations Universities base biocompatible polymer biomaterial compatibility cancer invasiveness career career networking clinical practice cytotoxicity design ethylene glycol experimental study functional mimics healing implantation improved in vivo in vivo Model innovation innovative technologies lung injury macrophage medical schools mortality multidisciplinary novel poly(lactide)polyacrylate porcine model pre-doctoral pressure prevent professor repaired response responsible research conduct seal sealant success symposium wound

项目摘要

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.

项目概要/摘要该奖学金将支持丹妮尔·菲茨杰拉德女士在波士顿大学 Mark Grinstaff 博士和马萨诸塞州 Yolonda Colson 博士共同赞助综合医院/哈佛医学院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，以及这种个性化的培训计划提供了独特的学习机会。生物材料领域具有关键的临床投入，并特别解决了她成为教授的职业目标作为她的一部分，格林斯塔夫博士和科尔森将继续定期与该研究员会面。三年计划并将为她提供必要的资源（空间、设备、物资、培训等）成功。在研究前沿，她的提案描述了新型可生物降解、生物相容性压力敏感具有可调节粘合强度的粘合剂（PSA），用于体内使用，克服了这一问题。目前 PSA 的局限性，仅与 Colson 和 Grinstaff 博士一起局部使用。肺泡胸膜瘘被认为是胸外科中一个重要且有问题的临床手术如今，与医疗保健费用增加和高死亡率相关的问题是，堵住此类泄漏已经成为可能。由于空间有限和瘘管内固有的压力梯度，这具有挑战性。 Fitzgerald 正在评估新型聚（1,2-甘油碳酸酯）（PGC），其功能类似于传统的聚丙烯酸酯 PSA，但具有可生物降解的碳酸酯键并降解为良性产品 - 例如，这些首创的聚合物为创造新型 PSA 和转变提供了机会。围绕我们控制和处理胸腔内伤口的能力的范式将被提议的实验。测试以下假设：这些基于 PGC 的压敏粘合剂将： 1) 在成分上表现出依赖的粘合强度与较大的分子量、较长的烷基呈正相关 2) 显示剥离强度，可在很宽的范围内调节与 Duct® 胶带类似的 Post-it® 便条性能；3) 能够将胶原蛋白支撑物固定到手术上；用于封闭肺部损伤的订书机或电纺聚丙交酯网状贴片她的具体目标是：目标 1。合成并表征一系列基于 PGC 的压敏粘合剂；目标 2. 评估 PGC 粘合胶原蛋白和 PLA 贴片在体外和体内的相容性；目标 3. 评估 PGC 粘合胶原蛋白和 PLA 贴片在猪模型中的性能重要的是，初步数据。支持这些假设，并建立了良好表征的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重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。