Immune-compatible Designs of Electronic Polymers for Implantable Devices with Suppressed Foreign-Body Responses

电子生物材料作为生物植入物越来越多地用于与生物系统直接接触，在活体人和动物体内。所产生的设备通常在记录、研究和调节生物过程和生理条件方面提供无与伦比的功能。然而，在生物植入下，这些材料的功能寿命通常受到免疫系统引起的异物反应的限制。解决这一问题的材料改进虽然备受期待，但由于缺乏对这种材料-生物学界面的免疫行为的基本知识，特别是不同材料结构的影响，在很大程度上受到阻碍。在这项研究中，为了缩小电子聚合物（一种与生物系统具有更高机械相容性的新兴电子材料）的差距，王博士建议开展基础生物材料与免疫系统相互作用行为的研究，特别是在细胞水平上。王博士将创建具有不同化学结构的电子聚合物，并进行体外细胞实验，以表征其在典型的异物反应过程中与不同类型免疫细胞和环境的相互作用行为。该研究将为理解不同材料设计特征对免疫反应途径的影响提供必要的数据，从而指导免疫兼容电子聚合物的未来发展。这些研究活动将为高分子科学、电子工程和免疫学的学生提供学习和训练的机会。在这个研究项目的支持下，芝加哥南部社区的高中将建立一个新的项目，让高中教师和学生都参与到生物材料的研究中来。研究和教育成果将通过同行评议的出版物、研讨会、会议报告和网站广泛传播。对于直接将合成材料与活体生物系统中的生物细胞和组织相结合的生物植入物，一个长期存在的挑战是免疫系统引发的普遍存在的异物反应。使用与生物组织具有更好机械相容性的电子聚合物是解决植入式电子免疫相容性问题的一个新兴和有前途的方向。然而，由于缺乏理解和策略，在不牺牲其他方面的前提下，有效地将免疫相容性和导电聚合物材料的分子设计结合起来，阻碍了进展。本研究旨在建立对不同共轭骨架和侧链结构的电子聚合物与蛋白质和不同免疫细胞之间相互作用行为的基本生物材料理解，从而产生整体的异体反应。具体来说，该研究将包括常用的共轭聚合物设计单元，以及新加入的免疫相容基团，以可能改善免疫相容性能。同时，对于这种新的免疫兼容电子聚合物设计，也将对其在电子和离子输运中的结构-性质关系进行研究。该研究成果有望为生物材料领域开辟一个新的研究方向，即在单一材料中结合高电子性能和免疫相容性。从广义上讲，这项研究将为实现长期生物相容性电子聚合物迈出突破性的一步，这将在很大程度上有利于用于医学诊断、疾病治疗和生物学研究的植入式电子技术领域。这项跨学科的研究将为不同阶段的学生提供培训机会，使他们成为新兴生物材料和电子领域的未来劳动力。该奖项反映了美国国家科学基金会的法定使命，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，被认为值得支持。

PART 1: NON-TECHNICAL SUMMARYElectronic biomaterials have been more and more heavily used in/as bioimplants to directly interface with biological systems, inside live human and animal bodies. The resulted devices typically provide unparalleled functions in recording, studying and modulating biological processes and physiological conditions. However, the functional longevity of these materials under bio-implantation is commonly limited by the foreign-body responses elicited by immune systems. The material improvements for solving this problem, though highly desired, have been largely hindered by the lack of fundamental knowledge about the immune behavior at such material-biology interfaces, particularly with the influences from different material structures. In this research, aiming at closing this gap on electronic polymers—an emerging class of electronic material with higher mechanical compatibility with biological systems, Dr. Wang proposes to carry out fundamental biomaterial research on their interaction behaviors with immune-systems, especially at the cellular level. Dr. Wang will create electronic polymers with varied chemical structures, and perform in vitro cell experiments to characterize their interaction behaviors with different types of immune cells and environment during the typical foreign-body response process. This research will provide essential data for understanding the influence of different material design features on immune reaction pathways, and therefore guide the future development of immune-compatible electronic polymers. The research activities will provide learning and training opportunities for students at the interface of polymer science, electrical engineering, and immunology. Supported by this research project, a new program will be established with high schools in Chicago’s south side community to bring both high school teachers and students into the biomaterials research. The research and education results will be disseminated broadly through peer-reviewed publications, seminars, conference presentations, and websites. PART 2: TECHNICAL SUMMARYFor bioimplants that directly interface synthetic materials with biological cells and tissues in live biological systems, a long-standing challenge to be resolved is the commonly existing foreign-body responses elicited by immune systems. An emerging and promising direction for solving the immune-compatibility problem for implantable electronics is to use electronic polymers that have better mechanical compatibility with biological tissues. However, progress has been hindered by the lack of understanding and strategies for effectively combining molecular designs for immune-compatibility and electrical conduction on polymeric materials, without sacrificing the other. This research aims to establish the fundamental biomaterial understanding about the interaction behaviors between electronic polymers of varied conjugated backbones and side-chain structures with proteins and different immune cells that make the overall foreign body responses. Specifically, the study will include both commonly used design units for conjugated polymers, and newly incorporated immune-compatible groups for the possible improvement of immune-compatible properties. At the same time, for such new immune-compatible designs of electronic polymers, studies will also be carried out on their structure-property relationships in both electron and ion transport. The outcome of the research can be expected to initiate a new research direction for the field of biomaterials, which focuses on combining high electronic performance and immune compatibility in a single material. Broadly, this research will make the groundbreaking steps for realizing long-term biocompatible electronic polymers, which will largely benefit the technological areas of implantable electronics for medical diagnosis, disease treatment and biological studies. This interdisciplinary research will provide training opportunities for students at different stages for becoming the future workforce in the emerging area of biomaterials and electronics.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.