仿生制备基于神经细胞选择性连接的电刺激响应导电高分子

Nerve injury and disorder cause significant losses of mobility and physical function. Neuroprosthetics and nerve regeneration electronic devices have been developed to substitute for or repair damaged motor, sensory, or cognitive modality, thereby recovering bodily functions. Bioelectronic devices are now being advanced toward electrically coupling with tissues at high selectivity, long-term stability and high resolution, while challenged by the invasiveness, implant-induced injury, and host-interface response. Electrically conductive polymers (ECPs) including PEDOT are likely to encounter the implant-induced inflammation although it might be not as severe as those for metals and inorganic semiconductors. The non-specific binding of ECPs is considered as one of the major reasons, as it is also recognized by the inflammation involved proteins and cells (microphage, microglia, etc). Toward resolving the inflammation issue, we propose here a series of cell-membrane inspired EDOT-based copolymers, which specifically recognizes cells with resisting non-specific binding. The unique features of our biomimetic approaches includes (1) the enrichment of zwitterionic group bearing EDOTs to resist the non-specific binding and reduce tissue response, and (2)the dynamic or static connection for neuron-targeted biomolecules to support neuron adhesion and function. The design to connect biomolecules by an electrostimuli-responsive linkage will make it possible to noninvasively decouple the strong neuron-substrate interaction when an implant revision is necessary. It should be emphasized here that the biomimetic approach would not damage the impedance of PEDOT, as zwitterionic groups contribute ionic conductivity. The emulsion electro-polymerization will be adopted to prepare the functional copolymers. The bio-inspired designs of the functionalized EDOT polymers will be evaluated by the performance to selectively couple to cells, and that to release cells by electrical stimuli both in vivo and in vitro. Hopefully, the bioinspired approaches proposed here could illuminate a potential way to synthesize organic conductive materials for long-term implantable and noninvasively removable electronic devices.

神经损伤和无序导致患者丧失活动性或身体机能。神经植入电子器件，包括神经假体和神经再生器件，可以取代和再生受损运动、感知及认知模式来治愈患者。神经电极作为器件和神经组织的接口，在器件记录传导神经信号、电刺激神经再生中扮演着决定性角色。本项目制备同时具备神经选择性连接和电刺激响应开关的"电响应释放神经细胞导电高分子"，通过在导电高分子上模仿细胞膜富集表达抗非特异性蛋白?细胞吸附的两性离子，同时引入神经靶向配体和蛋白，实现对神经细胞的选择性连接，有望显著降低组织反应；在此基础上，引入电刺激响应性耦合官能团，在保证器件与神经细胞选择性连接的前提下，实现其电响应关闭功能，有利于器件再植入时非损伤性移除旧电极。本项目通过复合神经靶向和电刺激开关的技术途径，有望能够克服现有电极材料的一些主要不足，为解决神经电子器件的长期稳定性和非损伤性移除问题提供一个有潜力的新方向。

通过本项目的四年研究，仿生制备了具有选择性连接和刺激响应性开关生物功能的“电响应释放神经细胞”导电高分子，实现了细胞从电极材料的可控释放，达到了预期研究目标。并突破了该仿生导电高分子及仿生绝缘材料与电极阵列的集成技术，初步完成了仿生导电高分子神经电极的制备，可用于长期稳定植入为前提的非损伤性神经电极移除。该研究结果可为植入神经电极长期植入稳定性及再植入难题提供一有潜力的解决办法，在植入神经电极、神经假体、植入电子药等生物医学领域具有较好的应用前景。