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

非技术概述生物医学粘合剂聚合物是具有通过粘合将两个组织表面连接在一起的能力的非金属材料。目标组织可以包括从硬组织（骨骼、牙齿、软骨）到软组织（大多数其他器官）的一切。生物医学粘合剂最常见的应用涉及替代传统的伤口闭合，如缝合线和斯台普斯。生物医学粘合剂还可用作止血剂以止血，密封剂以封闭组织之间的大空间间隙，伤口敷料以促进愈合，以及药物递送基质以有效且安全地将药物运输到体内。然而，这些现有的生物医学粘合剂产品具有显著的局限性。这些局限性包括粘合强度差、组织应用有限、固化速率释放差、应用的组织硬化以及围绕其基础材料聚合物的安全性问题。该项目将开发一种新的，定义明确的瓶刷聚合物，具有很强的粘附组织，药物输送能力，可降解性和生物相容性。该计划将建立多功能生物医学聚合物粘合剂的合成原理和结构-性能关系，以克服目前的局限性。这笔资金也将用于为HBCU本科生开发一个新的参与式夏季研究计划的教育目标。该计划将允许学生在PI实验室学习聚合物粘合剂的同时获得基础研究方法的知识。一个额外的合作夏季研究计划，重点是服务不足的学生，将提供最先进的研究机会，与其他著名的研究小组在著名的研究所。瓶刷聚合物含有连接到主链上的致密聚合物刷链。密集分布的聚合物刷形成三维圆柱形形状，并且与线性聚合物相比，可以在单位空间中包含增加的官能团群。因为瓶刷聚合物显示出独特的本体性质，例如低缠结、低模量和其它独特的粘弹性（例如，超软弹性体），瓶刷聚合物在过去十年中受到了相当大的关注。然而，以前的瓶刷聚合物研究由于合成挑战而较少关注粘合剂性能。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附/粘弹性特性表征的跨学科知识。特别地，在瓶刷聚合物上整合两个或更多个官能团同时仍然保持强粘附性仍然是一个具有挑战性的问题。本计画提出一种新的方法，借由控制自由基聚合与开环聚合来合成瓶刷主体结构。然后，致密瓶刷链的末端将被修饰以与没食子酸（强粘附）、厄他培南（抗生素）、5-Fu（抗癌剂）和奥沙利铂（抗癌剂）形成酯键。通过改变没食子酸/药物的链段比、聚合物总分子量和刷链长度来确定新型瓶刷生物医用粘合剂的详细结构-性能关系。将进行以下综合性能表征以完成结构-性能关系研究：粘附试验（搭接剪切强度试验和单轴压痕试验）、粘弹性（流变仪）、模量试验（拉伸试验）、生热试验（温度计）、药物释放试验、生物相容性试验和降解性试验。该提案的推广和教育目标是为HBCU中代表性不足的群体制定一项新的参与性教育研究计划。参与者将与FAMU-FSU工程学院的Chung研究小组以及其他着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知识价值和更广泛的影响审查标准进行评估而被认为值得支持。

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.