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：
10746743
负责人：
Danielle Fitzgerald
金额：
$ 4.77万
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/10746743
关键词：
Abraxane Acrylates Address Adhesions Adhesives Air Air Movements Alcohols Alveolar Area Bacterial Infections Bandage Benign Biocompatible Materials Biomedical Engineering 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 Endothelium Engineering Enrollment Epithelium Equipment 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 Macrophage Massachusetts Medical Mentors Modeling Molecular Weight Morbidity - disease rate Mus Oligonucleotides Operative Surgical Procedures Oral Performance Physicians Pleural Pleural cavity Polymers Prevention Procedures Property Research Research Project Grants 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 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 mechanical behavior medical schools mortality multidisciplinary novel organ injury poly(lactide)polyacrylate porcine model pre-doctoral pressure prevent professor repaired response responsible research conduct seal sealant success symposium wound

Abraxane Acrylates Address Adhesions Adhesives Air Air Movements Alcohols Alveolar Area Bacterial Infections Bandage Benign Biocompatible Materials Biomedical Engineering 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 Endothelium Engineering Enrollment Epithelium Equipment 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 Macrophage Massachusetts Medical Mentors Modeling Molecular Weight Morbidity - disease rate Mus Oligonucleotides Operative Surgical Procedures Oral Performance Physicians Pleural Pleural cavity Polymers Prevention Procedures Property Research Research Project Grants 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 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 mechanical behavior medical schools mortality multidisciplinary novel organ injury poly(lactide)polyacrylate porcine model pre-doctoral pressure prevent professor repaired response responsible research conduct seal sealant success symposium wound

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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.

项目摘要/摘要该奖学金将支持丹妮尔·菲茨杰拉德女士的跨学科研究和培训波士顿大学的马克·格林斯塔夫（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。该提案的培训方面包括四个支柱：跨学科研究，多学科心理，学术工程师科学家培训和专业发展。这个个性化的培训计划为学习提供了独特的机会具有关键临床输入的生物材料区域，并特别解决了她成为教授的职业目标在顶级大学。博士。 Grinstaff和Colson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，用品，培训等）成功。在研究方面，她的建议描述了可生物降解的新型生物相容性压力敏感的具有可调粘合强度的粘合剂（PSA），用于体内使用。这项创新技术克服了当前PSA的限制，仅局部使用。与博士一起。科尔森和格林斯塔夫，修复肺泡胸腔瘘被确定为胸手术中的重要且有问题的临床程序与医疗保健成本的提高和高死亡率相关。今天，这种泄漏的关闭是由于空间有限和瘘管上的遗传压力梯度而挑战。具体而言，女士菲茨杰拉德（Fitzgerald 聚丙烯酸酯PSA，但具有可生物降解的碳酸盐链接并降解为良性产品 - 例如，甘油，二氧化碳。这些第一届的聚合物提供了创建新的PSA和变化的机会围绕我们控制和管理胸前伤口的能力的范式。提出的实验将测试这些基于PGC的压力敏感粘合剂将：1）合成的假设依赖性粘合剂强度与较大的分子量，更长的烷基正相关连锁和立体缘； 2）显示果皮强度，可以在广泛的范围内调节 post-it®duct®胶带的注释，例如性能； 3）使胶原蛋白支撑固定到外科手术用于密封肺部损伤的订书机或静电涂离乳酸细胞贴片。她的具体目的是：目标1。合成并表征一系列基于PGC的压力敏感粘合剂；目标2。评估 PGC粘合剂胶原蛋白和PLA斑块在体外和体内的兼容性；并且，目标3。评估猪模型中PGC粘合剂胶原蛋白和PLA斑块的性能。重要的是，初步数据支持这些假设，并且建立了良好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的基本跨学科合作和专业知识，包括联合顾问/联合委员会和论文委员会成员。