Immunocompatible electronic polymers and devices for implantable sensors and stimulators that resist foreign-body responses

项目摘要 近几十年来，人体内的生物植入物已越来越多地被常规用于几乎每一个 生物医学专业，职能范围从病理学和生物学研究到医学治疗 恢复身体功能。在所有不同类型的生物植入物中，植入式电子设备 包括提供高度精确和程序化的信号转导的主要类别。但 包括电子设备在内的所有类型的生物植入物的寿命和稳定性都面临着一个共同的问题， 挑战，即胶原蛋白的过度向内生长和器械周围的炎症反应， 被称为“异物反应（FBR）"-一种对外来/合成免疫应答的免疫介导反应。 物质“入侵者”。即使是最成功的，FDA批准的已经使用了几十年的生物植入物， 在许多个体中可能会引起过度的FBR，这是在他们使用之前设备故障的主要原因。 所需的功能周期。为了解决这一普遍存在的重大挑战， 在开发用于抑制FBR的新生物材料设计方面已经做出了大量努力，该研究已经 几乎完全专注于绝缘型聚合物/水凝胶。为了继续解决下一个问题， 使用最有前途的材料家族的植入式电子设备的免疫兼容性问题- 电子聚合物，这是至关重要的，我们开发一套创新的材料设计，为电子 同时获得上级免疫相容性和高电性能的聚合物。我们建议 通过解决前所未有的免疫学接口的非凡挑战， 与半导体物理和聚合物科学，并在实验上结合联合收割机的方法，聚合物 合成、形态工程、器件制造、电特性、体外细胞试验和 活体动物试验。具体而言，本研究的重点包括四个方面：1）开发新的设计， 用于实现免疫相容化学性质的半导体和导电聚合物; 2）开发 用于实现组织水平弹性模量的“水凝胶结构”聚合物半导体 免疫相容性的物理性质; 3）这些免疫相容性的FBR的体外和体内研究 电子聚合物的设计; 4）结合材料和器件的发展，实现概念验证 免疫相容装置，包括电生理装置和基于晶体管的生物化学传感器。 基于植入式电子设备的高度重要的用途，我们设想实现免疫相容性 电子设备从这项研究将创造重大利益和深远的影响，以广泛的频谱 生物医学领域。

PROJECT SUMMARY In recent decades, bioimplants in human bodies have been more and more routinely used in almost every biomedical specialty, with the functions ranging from pathological and biological studies to medical treatments and restoration of body functions. Among all the different types of bioimplants, implantable electronic devices comprise a major category that provide highly accurate and programmed signal transductions. However, the longevity and stability of all types of bioimplants, including electronic devices, have been facing a common challenge, that is the excessive ingrowth of collagen and inflammation reactions around the device, which have been known as “foreign-body response (FBR)”—a type of immune-mediated reaction on foreign/synthetic material “invaders”. Even for the most successful, FDA-approved bioimplants that have been used for decades, excessive FBR can be provoked in many individuals, which is the primary cause of the device failure before their desired functional periods. For solving this commonly existing grand challenge, although a substantial amount of efforts has been made in the development of new biomaterial designs for suppressing FBR, the research has been almost exclusively focused on insulating-type polymers/hydrogels. To proceed to the next horizon of solving the immune-compatibility problem for implantable electronics using the most promising material family— electronic polymers, it is vitally important for us to develop a set of innovative material designs for electronic polymers for concurrently achieving superior immune compatibility and high electrical property. We propose to achieve this by intellectually addressing the extraordinary challenge of unprecedentedly interfacing immunology with semiconductor physics and polymer sciences, and experimentally combine the approaches of polymer synthesis, morphological engineering, device fabrication, electrical characterizations, in vitro cell tests, and in vivo animal tests. Specifically, the focuses of this research include four aspects: 1) developing new designs of semiconducting and conducting polymers for achieving immunocompatible chemical property; 2) developing “hydrogel-architecture” polymer semiconductors for realizing tissue-level elastic moduli for achieving immunocompatible physical property; 3) in vitro and in vivo study of the elicited FBR by these immunocompatible designs of electronic polymers; 4) combining the material and device developments to realize proof-of-concept immunocompatible devices, including electrophysiological devices, and transistor-based biochemical sensors. Based on the highly important uses of implantable electronics, we envision the realization of immunocompatible electronic devices from this research will create significant benefits and far-reaching impacts to a wide spectrum of biomedical areas.