Biodegradable, Biocompatible Pressure Sensitive Adhesives

项目摘要/摘要 *本提案描述了新的可生物降解、生物相容的压敏胶(PSA) 体内使用的粘合强度可调。因此，这种创新技术克服了现有技术的局限性 仅用于局部的PSA，并扩大了此类生物材料在患者护理中的应用范围。 为了强调这些新的PSA的效用，我们确定了两个重要的和有问题的临床程序 与医疗费用增加和高死亡率相关的胸部手术：肺泡修复- 还有支气管性胸膜瘘。今天，这种泄漏的封闭是具有挑战性的，因为在封闭的空间和 与瘘管内固有的压力梯度有关。存活直接关系到瘘管的成功闭合和 预防经瘘引起的胸膜感染。具体地说，我们正在评估新型聚(1，2-甘油酸) S和聚(1，2-甘油碳酸酯)S(PGCS)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，并可降解为良性产品--例如甘油、二氧化碳、乙醇。 这些首创的聚合物提供了创造一类新的PSA并改变范式的机会 关于我们控制和处理胸腔内伤口的能力。拟议的实验将测试HY- 假设这些PGC基压敏胶将：1)表现出成分依赖性 粘合强度与较大的相对分子质量、较长的烷基链呈正相关，以及 立体规则性；2)显示剥离强度，可在从Post-it®便笺到 Duct®类似胶带的性能；以及，3)能够将胶原支撑物固定到手术吻合器或 电纺聚乳酸网片封闭肺和支气管损伤。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，必须有跨学科的合作和专业知识。这个五年计划的具体目标 建议：目标1.合成和表征一系列PGC基压敏胶；目标2. 评价PGC-粘附胶原蛋白与聚乳酸贴片的体内外相容性及对细胞生长的抑制作用 细菌的体外迁移；以及，目的3.评价PGC-粘附胶原蛋白和聚乳酸贴片的性能 在活体猪模型中。

PROJECT SUMMARY/ABSTRACT * This proposal describes new biodegradable, biocompatible pressure sensitive adhesives (PSAs) with tunable adhesion strength for in vivo use. Thus, this innovative technology overcomes the limitation of current PSAs which are only used topically and broadens the scope of applications of such biomaterials in patient care. To highlight the utility of these new PSAs, we identified two significant and problematic clinical procedures in thoracic surgery associated with increases in health care costs and high mortality rates: the repair of alveolar- and broncho- pleural fistulae. Today, closure of such leaks is challenging due to use in a contained space and to an inherent pressure gradient across the fistula. Survival is directly related to successful fistula closure and prevention of pleural infection through the fistula. Specifically, we are evaluating novel poly(1,2-glyceric acid carbonate)s and 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, ethanol. 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 hy- potheses 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 and bronchial injuries. 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. The specific aims of this five-year proposal 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 inhibition of bacteria migration in vitro; and, Aim 3. Evaluate the performance of the PGC-adhesive collagen and PLA patch in an in vivo porcine model.