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

项目总结 近几十年来，人体内的生物植入物已经越来越多地被常规地应用于几乎每一个 生物医学专业，具有从病理、生物研究到医疗的各种功能 和身体功能的恢复。在所有不同类型的生物植入物中，可植入的电子设备 包括提供高精度和程序化信号换能器的主要类别。然而， 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一直面临着共同的 挑战是胶原蛋白的过度内化和设备周围的炎症反应，这对 一直被称为“异物反应(FBR)”--一种免疫介导的异物/合成反应 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， 许多人可能会引发过多的FBR，这是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，尽管有大量的 在为抑制FBR而开发新的生物材料设计方面已经做出了许多努力，该研究已经 几乎完全集中在绝缘型聚合物/水凝胶上。进入下一个解决问题的地平线 使用最有希望的材料家族的植入式电子产品的免疫兼容性问题- 对于电子聚合物来说，开发一套创新的电子聚合物材料设计是至关重要的 用于同时实现卓越的免疫兼容性和高电学性能的聚合物。我们建议 通过理智地解决前所未有的免疫学接口的非凡挑战来实现这一点 与半导体物理和聚合物科学相结合，并在实验上结合聚合物的方法 合成，形态工程，器件制造，电学特性，体外细胞测试，以及 活体动物实验。具体地说，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 实现组织级弹性模数的“水凝胶-结构”聚合物半导体 免疫相容的物理性质；3)免疫相容的体内外研究 电子聚合物设计；4)材料与器件开发相结合，实现概念验证 免疫兼容设备，包括电生理设备和基于晶体管的生化传感器。 基于植入式电子设备的重要用途，我们展望了免疫兼容的实现。 这项研究的电子设备将产生巨大的好处和广泛而深远的影响 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.