Excellence in Research: Designing biodegradable bottlebrush polymers based on their structure-property relationships for strong tissue adhesion and drug delivery

非技术摘要生物医学粘合聚合物是一种非金属材料，它具有通过粘合将两个组织表面连接在一起的能力。目标组织可能包括从硬组织(骨、牙齿、软骨)到软组织(大多数其他器官)的一切。生物医用粘合剂最常见的应用包括替换传统的伤口闭合，如缝合线和钉子。生物医用粘合剂还可以用作止血剂止血，密封剂用于弥合组织之间的巨大间隙，伤口敷料用于促进愈合，药物输送基质用于高效和安全地将药物输送到体内。然而，这些现有的生物医用粘合剂产品都有很大的局限性。这些限制包括粘合强度差、组织应用有限、释放速度超过固化速度、应用组织僵硬以及围绕其基础材料聚合物的安全问题。该项目将开发一种新的、定义明确的瓶刷聚合物，该聚合物具有强大的组织粘附性、药物输送能力、降解性和生物兼容性。拟议的计划将建立多功能生物医用聚合物粘合剂的合成原理和结构-性能关系，以克服目前的限制。这笔资金还将用于为HBCU本科生开发一个新的参与式暑期研究项目的教育目标。该项目将允许学生在PI的实验室学习聚合物粘合剂的同时获得基本研究方法的知识。一个额外的合作暑期研究项目，重点是服务不足的学生，将提供与著名研究所的其他著名研究小组进行最新研究的机会。技术概述瓶刷聚合物含有连接到主链上的致密聚合物刷链。密集填充的聚合物刷形成三维圆柱形，并且与线性聚合物相比，可以在单位空间中包含更多的官能团。由于瓶刷聚合物表现出独特的本体性质，如低缠结、低弹性和其他独特的粘弹性性质(如超软弹性体)，瓶刷聚合物在过去十年中受到了极大的关注。然而，由于合成方面的挑战，以往的瓶刷聚合物研究较少关注胶粘剂的性能。这些挑战包括制备定义明确的聚合物结构，以及缺乏关于复杂聚合物合成和粘接/粘弹性特性表征的跨学科知识。特别是，在瓶刷聚合物上整合两个或更多官能团，同时仍保持强大的附着力仍然是一个具有挑战性的问题。本课题提出了一种采用可控自由基聚合和开环聚合合成瓶刷主体结构的新方法。然后，密集的瓶刷链的末端将被修饰，以形成与五倍子(强粘附性)、厄他培南(抗生素)、5-FU(抗癌剂)和奥沙利铂(抗癌剂)的酯键。新型瓶刷生物医用胶粘剂的详细结构-性能关系将通过二甘醇/药物的链段比、聚合物总相对分子质量和刷子链长的变化来确定。为完成结构-性能关系研究，将进行以下综合性能表征：附着力测试(搭接剪切强度测试和单轴压痕测试)、粘弹性测试(流变仪)、模数测试(拉伸测试仪)、生热测试(温度计)、药物释放测试、生物相容性测试和降解性测试。这项提议的外展和教育目标是为HBCU中代表性不足的群体制定一个新的参与式教育研究方案。参与者将与FAMU-FSU工程学院的Chung研究小组以及其他著名大学的其他合作研究小组一起进行真实世界的生物材料研究。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

NONTECHNICAL SUMMARYBiomedical adhesive polymers are nonmetallic materials which possess the ability to join two tissue surfaces together via bonding. Targeted tissues may include everything from hard tissues (bone, tooth, cartilage) to soft tissues (most other organs). The most common application of biomedical adhesives involves the replacement of conventional wound closures such as sutures and staples. Biomedical adhesives can be also used as hemostatic agents to stop bleeding, sealants to close large space gap between tissues, wound dressing to enhance healing, and drug delivery matrices to transport drugs efficiently and safely into the body. However, these existing biomedical adhesives products have significant limitations. These limitations include poor adhesion strength, limited tissue application, poor release over curing rate, applied tissues stiffening, and safety concerns surrounding their base materials, polymers. This project will develop a new, well-defined bottlebrush polymer that has strong adhesion to tissue, drug delivery capabilities, degradability, and biocompatibility. The proposed program will establish synthetic principles and structure-property relationships for multifunctional biomedical polymeric adhesives to overcome current limitations. This funding will also be used for the educational goal of developing a new participatory summer research program for HBCU undergraduate students. The program will allow students to acquire knowledge on basic research methods while studying polymeric adhesives at the PI’s lab. An additional collaborative summer research program, focused on underserved students, will provide state of the art research opportunities with other prestigious research groups at prominent institutes. TECHNICAL SUMMARY Bottlebrush polymers contain dense polymer brush chains linked to a backbone. The densely populated polymer brushes form a three-dimensional cylindrical shape and can encompass an increased population of functionalities in a unit space compared to linear polymers. Because the bottlebrush polymer demonstrates unique bulk properties such as low entanglement, low modulus, and other unique viscoelastic properties (e.g., supersoft elastomer), the bottlebrush polymer has received considerable attention in the past decade. However, previous bottlebrush polymer research has paid less attention to adhesive properties due to synthetic challenges. These challenges include the preparation of well-defined polymer structures and the lack of interdisciplinary knowledge on sophisticated polymer synthesis and adhesion/viscoelastic property characterization. In particular, integration of two or more functional groups on a bottlebrush polymer while still maintaining strong adhesion remains a challenging issue. In this project, a new approach is proposed by using both controlled radical polymerization and ring opening polymerization to synthesize the bottlebrush main structure. Then, a terminal of the dense bottlebrush chains will be modified to form ester linkages to gallol (strong adhesion), Ertapenem (antibiotics), 5-Fu (anticancer agent), and Oxaliplatin (anticancer agent). The detailed structure-property relationships of the new bottlebrush biomedical adhesive will be determined through the variation of the segmental ratio of gallol/drug, total polymer molecular weight, and brush chain lengths. The following comprehensive property characterizations will be performed to complete the structure-property relationship study: adhesion tests (lap shear strength tests and uniaxial indentation tests), viscoelastic property (rheometer), modulus test (tensile tester), heat generation test (thermometer), drug release test, biocompatibility test, and degradability test. The outreach and educational goals of this proposal is to develop a new participatory educational research program for underrepresented groups in HBCU. The participants will conduct real-world biomaterials research with Chung research group at FAMU-FSU college of engineering and with other collaborating research groups at other prestigious universities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.