WO2022233140A1 - 一种植入体界面修饰材料、植入体及植入体的制备方法 - Google Patents

一种植入体界面修饰材料、植入体及植入体的制备方法 Download PDF

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WO2022233140A1
WO2022233140A1 PCT/CN2021/138553 CN2021138553W WO2022233140A1 WO 2022233140 A1 WO2022233140 A1 WO 2022233140A1 CN 2021138553 W CN2021138553 W CN 2021138553W WO 2022233140 A1 WO2022233140 A1 WO 2022233140A1
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implant
film material
interface
implant body
polymer
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阎梦萦
王璐璐
曹燚
鲁艺
王立平
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Shenzhen Institute of Advanced Technology of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/06—Coatings containing a mixture of two or more compounds

Definitions

  • the invention belongs to the technical field of life science, and particularly relates to an implant interface modification material, an implant and a preparation method of the implant.
  • the human brain can be regarded as the most complex organizational structure, and the nervous system is like an extremely complex communication network that exists in the human body, controlling everything that happens in the body. About 100 billion neurons in the brain transmit information through complex potentials, understanding neural network activity, and analyzing the connection loop between the central nervous system and the peripheral nervous system are of great significance for understanding the mechanism of many related diseases and treatment methods.
  • Implantable multi-level array is an existing common means to record the firing time and waveform of neuronal action potentials and provide neural information.
  • neuronal cells are also stimulated through these implanted multi-level array devices, thereby regulating the information transmission between neuronal cells, seeking to change the abnormal neural network activity of patients, thereby relieving symptoms or treating diseases.
  • the current neural electrical interface still faces great challenges in the research and regulation of neural circuits in vivo.
  • the existing implant neural interface modification mostly uses electrical direct deposition of 3,4-ethylenedioxythiophene (EDOT) and polymer Sodium styrene sulfonate (PSS) to reduce the electrode impedance and improve its signal recording performance.
  • EDOT 3,4-ethylenedioxythiophene
  • PSS polymer Sodium styrene sulfonate
  • the interfacial modification of 3,4-ethylenedioxythiophene (EDOT) and sodium polystyrene sulfonate (PSS) by electrodeposition can only improve implant performance, stability and biocompatibility in the short term. Neither is ideal.
  • the specific manifestations are: 1) The biocompatibility is not ideal, and long-term implantation will trigger an inflammatory response at the neural interface, resulting in a sharp decline in the performance of the implant; 2) The deposition stability of EDOT/PSS is very poor, and it is easy to modify the neural interface 3) Most of them are non-flexible materials, and it is difficult to apply to the peripheral nervous system.
  • the purpose of the present invention is to provide an implant interface modification material, an implant and a preparation method of the implant.
  • the implant of the invention has ultra-high biocompatibility, reduces the inflammatory response caused by the implant, maintains the good performance of the implant after long-term implantation, improves the performance stability of the implant, minimizes trauma, High-density and large-scale recording of neural signals to achieve long-term high-throughput and high-precision acquisition and regulation of neural network activities; the modified neural interface is not easy to fall off; it is helpful for the study of mechanisms related to peripheral neural circuits.
  • the technical scheme adopted in the present invention is as follows: on the one hand, the present invention provides a film material, which includes an anion-rich polymer and a polymer with good film-forming properties;
  • the anion-rich polymer includes one of sodium polyacrylate, polymethacrylic acid, polymethacrylate, polyvinylsulfonic acid, polyvinylsulfonate, polystyrenesulfonic acid, and polystyrenesulfonate. one or more;
  • the polymer with good film-forming properties includes one or more of polyvinyl alcohol, polyvinylidene fluoride, polyacrylonitrile, and chitosan.
  • the molar ratio of the anion-rich polymer to the polymer with good film-forming property is 0.1-10.
  • the present invention provides an implant interface modification material, comprising any of the above-mentioned thin film materials and 3,4-ethylenedioxythiophene.
  • the present invention provides an implant, which sequentially includes an implant body, a film material covering the desired modified interface of the implant body, and 3,4-ethylenedioxythiophene from the inside to the outside; covering
  • the thin film material required to modify the interface of the implant body is any of the above thin film materials.
  • the thickness of the thin film material covering the interface to be modified on the implant body is based on the actual situation, as long as it does not cause an electrode short circuit; preferably, it is 0.1-200 microns.
  • the implant body includes a pin header, a silicon tube, and a metal electrode wire.
  • the present invention provides a method for preparing any of the above implants, comprising the following steps: 1) reacting an anion-rich polymer with a polymer with good film-forming properties to form a film material;
  • the temperature of the heating reaction in a1 is 80-95°C, and the time of the heating reaction is more than 12h;
  • the drying temperature in a2 is 60-80°C, and the drying time is 6-12h;
  • the re-drying temperature in a2 shall not be higher than the phase transition temperature of the liquid film material raw material, and the re-drying time is 6-12h;
  • the solvent used for swelling described in a2 is a PBS solution
  • the concentration of the 3,4-ethylenedioxythiophene solution in a3 is 1mM-25mM;
  • the process conditions of the electrodeposition in a3 are a voltage of 0.6-2V and a time of 20-300s.
  • the temperature of the heating reaction in b1 is 80-95°C, and the time of the heating reaction is more than 12h;
  • the drying temperature in b2 is 60-80°C, and the drying time is 6-12h;
  • the re-drying temperature in b2 shall not be higher than the phase transition temperature of the liquid film material raw material, and the re-drying time is 6-12h;
  • the solvent used for swelling described in b2 is a PBS solution
  • the concentration of the 3,4-ethylenedioxythiophene solution in b3 is 1mM-25mM;
  • the process conditions for electrodeposition in b3 are a voltage of 0.6-2V and a time of 20-300s.
  • the beneficial effects of the present invention are: 1) The present invention adopts a new type of neural interface technology, which uses an anion-rich polymer and another polymer with good film-forming properties to react to synthesize a new film material, and then undergo electro The chemical process forms a new neural interface modification, the biocompatibility is significantly improved, the inflammatory response of the neural interface is significantly reduced, the wound surface is small, the performance of the implant can be maintained for a long time, and more and stronger neural signals can be recorded; 2) New The thin film of EDOT forms a structurally stable conductive polymer after the deposition of EDOT, the modification is not easy to fall off at the nerve interface, and the biocompatibility is far better than the direct deposition of EDOT/PSS; 3) The interface modification material has a certain flexibility and can be subcutaneously in vivo. Attached, can be applied to the peripheral nervous system.
  • Fig. 1 is the physical schematic diagram of the liquid film material in Example 1 of the present invention.
  • Fig. 2 is the actual schematic diagram of the film after the liquid film material is dried and immersed in the PBS solution and swelled in the embodiment of the present invention 1;
  • Fig. 3 is the physical schematic diagram of depositing EDOT after the implant body interface wraps film in Example 1 of the present invention
  • Fig. 4 shows the results of the stability comparison experiment in Example 2 of the present invention: the control group in the left picture is the direct deposition of PSS/EDOT on the conductive glass, the experimental group in the right picture is the conductive glass wrapped with a thin film and then the EDOT is deposited, and the two groups are deposited in PBS at the same time After soaking and rinsing in the solution, the interface modification material of the control group fell off earlier than the experimental group;
  • FIG. 5 is a comparison diagram of the signals recorded by the long-term implantation of the implant in the mouse brain in Example 3 of the present invention.
  • Example 6 is a comparison diagram of immunohistochemical analysis results after long-term implantation of implants in mice in Example 4 of the present invention.
  • Preparation of film material Mix sodium polystyrene sulfonate and polyvinyl alcohol, and react in an oil bath at 80° C. for more than 12 hours to obtain a liquid film material, as shown in Figure 1.
  • the liquid film material was evenly spread on the glass slide, then dried at 60-80°C for 6-12 hours, and then soaked in PBS solution for 12-48 hours to swell.
  • the schematic diagram of the film after swelling in PBS solution is shown in Figure 2.
  • Experimental group Mix sodium polystyrene sulfonate and polyvinyl alcohol, and react in an oil bath at 80°C for more than 12 hours to obtain a liquid film material; spread the liquid film material evenly on the glass slide, and then dry it at 60 ⁇ 80°C 6-12h, then soaked in PBS solution to swell until the film falls off. After the film falls off, wrap it on the conductive glass ITO. After drying at 60°C-80°C, the film is attached to the conductive glass ITO; The conductive glass ITO of the film was immersed in EDOT solution (concentration of 1mM-25mM), and electrodeposited by electrochemical workstation, voltage 0.9v, time 300s.
  • EDOT solution concentration of 1mM-25mM
  • Control group Conductive glass ITO was immersed in PSS/EDOT solution (PSS concentration 1mM-25mM, EDOT concentration 1mM-25mM), electrodeposited by electrochemical workstation, voltage 0.9v, time 300s.
  • control group and the experimental group were soaked and rinsed in the PBS solution at the same time, and the results of the stability comparison experiment were shown in Figure 4: the interface modification material of the control group fell off earlier than the experimental group.
  • Experimental group Mix sodium polystyrene sulfonate and polyvinyl alcohol, and react in an oil bath at 80°C for more than 12 hours to obtain a liquid film material; wrap the electrode with this film material, and immerse the electrode wrapped with the film in EDOT solution (concentration: 1mM-25mM), electrodeposition by electrochemical workstation, voltage 0.6-2V, time 20-300s.
  • EDOT solution concentration: 1mM-25mM
  • Control group The electrode was immersed in PSS/EDOT solution (PSS concentration 1mM-25mM, EDOT concentration 1mM-25mM), electrodeposited by electrochemical workstation, voltage 0.6-2V, time 20-300s.
  • PSS/EDOT solution PSS concentration 1mM-25mM, EDOT concentration 1mM-25mM
  • the experimental group and the control group were implanted into the brains of mice respectively, and electrophysiological signal recording was performed after 12 weeks. The results are shown in Figure 5.
  • the experimental group can record more signals than the control group, and the signal intensity is also higher than that of the control group.
  • Experimental group The sodium polystyrene sulfonate and polyvinyl alcohol were mixed, and the oil bath was reacted at 80 °C for more than 12 hours to obtain a liquid film material; the platinum wire was wrapped with this film material, and the platinum wire wrapped with the film was immersed in EDOT solution ( The concentration is 1mM-25mM), electrodeposition is carried out by electrochemical workstation, voltage 0.6-2V, time 20-300s.
  • Control group The platinum wire was immersed in PSS/EDOT solution (PSS concentration 1mM-25mM, EDOT concentration 1mM-25mM), electrodeposited by electrochemical workstation, voltage 0.6-2V, time 20-300s.
  • PSS/EDOT solution PSS concentration 1mM-25mM, EDOT concentration 1mM-25mM
  • the experimental group and the control group were implanted into mice respectively, and immunohistochemical staining was performed after 12 weeks. The results are shown in Figure 6.
  • the experimental group had less inflammatory reaction and better biocompatibility.

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Abstract

本发明公开了一种植入体界面修饰材料、植入体及植入体的制备方法，植入体界面修饰材料，包括薄膜材料、3,4-乙烯二氧噻吩；薄膜材料，包括富含阴离子的聚合物、成膜性好的聚合物。植入体，从内到外依次包括植入体主体、覆盖于所述植入体主体所需修饰界面的薄膜材料、3,4-乙烯二氧噻吩。本申请植入体生物相容性显著提高，神经界面炎性反应显著减弱，创面小，能长期保持植入体的性能，可记录到更多更强的神经信号；新的薄膜沉积EDOT后形成结构稳定的导电聚合物，修饰在神经界面不易脱落，生物相容性也远优于EDOT/PSS的直接沉积；该界面修饰材料有一定的柔韧性，可以体内皮下贴附，可应用于外周神经系统。

Description

一种植入体界面修饰材料、植入体及植入体的制备方法 技术领域
本发明属于生命科学技术领域，具体涉及一种植入体界面修饰材料、植入体及植入体的制备方法。
 背景技术
人类的大脑可以算是最复杂的组织结构，神经系统就像是存在于人体中的一个极其复杂的通信网络，控制着身体内发生的每一件事。大脑中约有1000亿个神经元通过复杂的电位传输信息，了解神经网络活动，解析中枢神经系统与外周神经系统的连接环路，对于明白许多相关疾病机理以及治疗方法都有着非凡的意义。
植入式多电级阵列是现有的记录神经元动作电位发放时间和波形，提供神经信息的常用手段。另一方面也会通过这些植入的多电级阵列装置对神经元细胞进行刺激，由此来调控神经元细胞间的信息传递，寻求改变患者的异常神经网络活动，从而缓解症状或治疗疾病。
目前的神经电级界面在体内神经环路研究和调控方面尚面临着巨大挑战，现有的植入体神经界面修饰中多采用电级直接沉积3,4-乙烯二氧噻吩（EDOT）和聚苯乙烯磺酸钠（PSS）以降低电级阻抗，提高其信号记录性能。然而，采用电级直接沉积3,4-乙烯二氧噻吩（EDOT）和聚苯乙烯磺酸钠（PSS）的界面修饰方式只能短期内提高植入体性能，其稳定性和生物相容性均不理想。具体表现为：1）生物相容性尚不理想，长期植入会引发神经界面的炎性反应，导致植入体性能急剧下降；2）EDOT/PSS的沉积稳定性很差，修饰神经界面容易脱落；3）多为非柔性材料，应用于外周神经系统有一定困难。
 技术问题
为了解决上述背景技术中所提出的技术问题，本发明的目的在于提供一种植入体界面修饰材料、植入体及植入体的制备方法。本发明植入体具有超高的生物相容性，减少了植入体所引发的炎症反应，长期植入仍保持植入体的良好性能，提高了植入体性能稳定性，创伤微小化、高密度大范围记录神经信号，实现长期高通量高精度采集与调控神经网络活动；修饰神经界面不易脱落；助于外周神经环路相关机制的研究。
为了达到上述目的，本发明所采用的技术方案为：一方面，本发明提供了一种薄膜材料，包括富含阴离子的聚合物、成膜性好的聚合物；
所述富含阴离子的聚合物包括聚丙烯酸钠、聚甲基丙烯酸、聚甲基丙烯酸盐、聚乙烯磺酸、聚乙烯磺酸盐、聚苯乙烯磺酸、聚苯乙烯磺酸盐中的一种或多种；
所述成膜性好的聚合物包括聚乙烯醇、聚偏氟乙烯、聚丙烯腈、壳聚糖中的一种或多种。
进一步地，所述富含阴离子的聚合物、成膜性好的聚合物的摩尔比为0.1-10。
另一方面，本发明提供了一种植入体界面修饰材料，包括上述任一所述的薄膜材料、3,4-乙烯二氧噻吩。
另一方面，本发明提供了一种植入体，从内到外依次包括植入体主体、覆盖于所述植入体主体所需修饰界面的薄膜材料、3,4-乙烯二氧噻吩；覆盖于所述植入体主体所需修饰界面的薄膜材料为上述任一所述的薄膜材料。
进一步地，覆盖于所述植入体主体所需修饰界面的薄膜材料的厚度根据实际情况，不造成电极短路即可；优选为0.1-200微米。
进一步地，所述植入体主体包括排针、硅管、金属电极丝。
再一方面，本发明提供了一种上述任一所述的植入体的制备方法，包括以下步骤：1）将富含阴离子的聚合物与成膜性好的聚合物反应形成薄膜材料；
2）在植入体主体所需修饰界面覆盖薄膜材料；
3）在薄膜材料表面电沉积3,4-乙烯二氧噻吩得到所述植入体。
进一步地，具体包括以下步骤：
a1）将富含阴离子的聚合物与成膜性好的聚合物进行混合，加热反应，得到液体薄膜材料；
a2）在植入体主体所需修饰界面轻沾液体薄膜材料或者将液体薄膜材料均匀涂抹至植入体主体所需修饰界面，然后烘干，烘干后将其充分溶胀，溶胀过后重新烘干（如果直接植入，会在组织液中溶胀，漂浮，脱离基底。烘干后溶胀，溶胀过后再重新烘干会更加贴紧基底不脱落），得到所需修饰界面覆盖薄膜材料的植入体主体；
a3）将所需修饰界面覆盖薄膜材料的植入体主体浸入3,4-乙烯二氧噻吩溶液中进行电沉积得到所述植入体（沉积后即已完成植入体主体的神经界面修饰，可植入动物体内进行相关实验应用）；
或b1）将富含阴离子的聚合物与成膜性好的聚合物进行混合，加热反应，得到液体薄膜材料；
b2）先将液体薄膜材料均匀涂抹至玻片表面或适宜的模具中，然后烘干，烘干后再溶胀至薄膜脱落，之后剪取适宜大小的薄膜平铺至植入体主体所需修饰的界面，再重新烘干，得到所需修饰界面覆盖薄膜材料的植入体主体；
b3）将所需修饰界面覆盖薄膜材料的植入体主体浸入3,4-乙烯二氧噻吩溶液中进行电沉积得到所述植入体（沉积后即已完成植入体主体的神经界面修饰，可植入动物体内进行相关实验应用）。
进一步地，a1中所述加热反应的温度为80-95℃，所述加热反应的时间为12h以上；
优选地，a2中所述烘干的温度为60-80℃，所述烘干的时间为6-12h；
优选地，a2中所述重新烘干的的温度不得高于液体薄膜材料原材料的相变温度，所述重新烘干的时间为6-12h；
优选地，a2中所述溶胀所用的溶剂为PBS溶液；
优选地，a3中3,4-乙烯二氧噻吩溶液的浓度为1mM-25mM；
优选地，a3中所述电沉积的工艺条件为电压0.6-2V，时间20-300s。
进一步地，b1中所述加热反应的温度为80-95℃，所述加热反应的时间为12h以上；
优选地，b2中所述烘干的温度为60-80℃，所述烘干的时间为6-12h；
优选地，b2中所述重新烘干的的温度不得高于液体薄膜材料原材料的相变温度，所述重新烘干的时间为6-12h；
优选地，b2中所述溶胀所用的溶剂为PBS溶液；
优选地，b3中3,4-乙烯二氧噻吩溶液的浓度为1mM-25mM；
优选地，b3中所述电沉积的工艺条件为电压0.6-2V，时间20-300s。
 有益效果
本发明的有益效果是：1）本发明采用了一种新型神经界面技术，采用富含阴离子的聚合物和另一种成膜性好的聚合物反应合成一种新的薄膜材料，再经过电化学过程形成新的神经界面修饰，生物相容性显著提高，神经界面炎性反应显著减弱，创面小，能长期保持植入体的性能，可记录到更多更强的神经信号；2）新的薄膜沉积EDOT后形成结构稳定的导电聚合物，修饰在神经界面不易脱落，生物相容性也远优于EDOT/PSS的直接沉积；3）该界面修饰材料有一定的柔韧性，可以体内皮下贴附，可应用于外周神经系统。
 附图说明
图1为本发明实施例1中液体薄膜材料的实物示意图；
图2为本发明实施例1中液体薄膜材料烘干后再浸泡入PBS溶液中溶胀后的薄膜实物示意图；
图3为本发明实施例1中植入体主体界面包裹薄膜后沉积了EDOT的实物示意图；
图4为本发明实施例2中稳定性对比实验结果图：左图对照组为导电玻璃上直接沉积PSS/EDOT，右图实验组为导电玻璃上包裹了薄膜再沉积EDOT，两组同时在PBS溶液中浸泡、冲洗，对照组的界面修饰材料比实验组先脱落；
图5为本发明实施例3中植入体长期埋入老鼠脑内记录到的信号情况对比图；
图6为本发明实施例4中老鼠体内长期植入植入体后免疫组化分析结果对比图。
 本发明的实施方式
本发明的具体方案阐述中仅具体地表达了本发明的几种实施方式，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，该新型界面技术并不局限使用于外周神经的研究，还可以用于中枢神经及其他神经相关疾病病理机制研究药物开发等，以及其他相似原理修饰神经界面的方式，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
为了更好地理解本发明的内容，下面结合具体实施方法对本发明内容作进一步说明，但本发明的保护内容不局限以下实施例。
实施例1
薄膜材料的制备：将聚苯乙烯磺酸钠与聚乙烯醇进行混合，油浴80℃反应12小时以上，得到液体薄膜材料，实物示意图如图1所示。
将液体薄膜材料均匀涂抹至载玻片上，然后在60~80℃烘干6-12h，之后再浸泡入PBS溶液中溶胀12-48h，PBS溶液中溶胀后的薄膜实物示意图如图2所示。
在铂丝所需修饰界面轻沾液体薄膜材料，然后在60~80℃烘干6-12h，烘干后在PBS溶液中充分溶胀，溶胀过后在60~80℃重新烘干6-12h，得到所需修饰界面覆盖薄膜材料的铂丝（薄膜材料的厚度根据实际情况，不造成电极短路即可）；将所需修饰界面覆盖薄膜材料的铂丝浸入浓度为1mM-25mM的3,4-乙烯二氧噻吩溶液中通过电化学工作站进行电沉积，电压0.6-2v，时间20-300s，得到植入体。植入体实物图示意图如图3所示。
实施例2
实验组：将聚苯乙烯磺酸钠与聚乙烯醇进行混合，油浴80℃反应12小时以上，得到液体薄膜材料；将液体薄膜材料均匀涂抹至载玻片上，然后在60~80℃烘干6-12h，之后再浸泡入PBS溶液中溶胀至薄膜脱落，薄膜脱落下来后把它包裹在导电玻璃ITO上，60℃-80℃烘干后，薄膜贴附在导电玻璃ITO上；将包裹了薄膜的导电玻璃ITO浸入EDOT溶液（浓度为1mM-25mM）中，通过电化学工作站进行电沉积，电压0.9v，时间300s。
对照组：导电玻璃ITO浸泡入PSS/EDOT溶液（PSS浓度1mM-25mM, EDOT浓度 1mM-25mM），通过电化学工作站进行电沉积，电压0.9v，时间300s。
将对照组和实验组同时在PBS溶液中浸泡、冲洗，稳定性对比实验结果如图4所示：对照组的界面修饰材料比实验组先脱落。
实施例3
实验组：将聚苯乙烯磺酸钠与聚乙烯醇进行混合，油浴80℃反应12小时以上，得到液体薄膜材料；用此薄膜材料包裹电极，将包裹了薄膜的电极浸入EDOT溶液（浓度为1mM-25mM），通过电化学工作站进行电沉积，电压0.6-2V，时间20-300s。
对照组：将电极浸泡入PSS/EDOT溶液（PSS浓度1mM-25mM, EDOT浓度 1mM-25mM），通过电化学工作站进行电沉积，电压0.6-2V，时间20-300s。
将实验组和对照组分别植入老鼠脑内，12周后进行电生理信号记录，结果如图5所示，实验组可以记录到的信号多于对照组，信号强度也高于对照组。
实施例4
实验组：将聚苯乙烯磺酸钠与聚乙烯醇进行混合，油浴80℃反应12小时以上，得到液体薄膜材料；用此薄膜材料包裹铂丝，将包裹了薄膜的铂丝浸入EDOT溶液（浓度为1mM-25mM），通过电化学工作站进行电沉积，电压0.6-2V，时间20-300s。
对照组：将铂丝浸泡入PSS/EDOT溶液（PSS浓度1mM-25mM, EDOT浓度 1mM-25mM），通过电化学工作站进行电沉积，电压0.6-2V，时间20-300s。
将实验组和对照组分别植入老鼠体内，12周后进行免疫组化染色分析，结果如图6所示，实验组的炎性反应较小，其生物相容性较优。
以上所述仅为本发明的具体实施方式，不是全部的实施方式，本领域普通技术人员通过阅读本发明说明书而对本发明技术方案采取的任何等效的变换，均为本发明的权利要求所涵盖。

Claims (10)

  1. 一种薄膜材料，其特征在于，包括富含阴离子的聚合物、成膜性好的聚合物；
    所述富含阴离子的聚合物包括聚丙烯酸钠、聚甲基丙烯酸、聚甲基丙烯酸盐、聚乙烯磺酸、聚乙烯磺酸盐、聚苯乙烯磺酸、聚苯乙烯磺酸盐中的一种或多种；
    所述成膜性好的聚合物包括聚乙烯醇、聚偏氟乙烯、聚丙烯腈、壳聚糖中的一种或多种。
  2. 根据权利要求1所述的薄膜材料，其特征在于，所述富含阴离子的聚合物、成膜性好的聚合物的摩尔比为0.1-10。
  3. 一种植入体界面修饰材料，其特征在于，包括权利要求1-2任一项所述的薄膜材料、3,4-乙烯二氧噻吩。
  4. 一种植入体，其特征在于，从内到外依次包括植入体主体、覆盖于所述植入体主体所需修饰界面的薄膜材料、3,4-乙烯二氧噻吩；覆盖于所述植入体主体所需修饰界面的薄膜材料为权利要求1-2任一项所述的薄膜材料。
  5. 根据权利要求4所述的植入体，其特征在于，覆盖于所述植入体主体所需修饰界面的薄膜材料的厚度为0.1-200微米。
  6. 根据权利要求4所述的植入体，其特征在于，所述植入体主体包括排针、硅管、金属电极丝。
  7. 权利要求4-6任一项所述的植入体的制备方法，其特征在于，包括以下步骤：1）将富含阴离子的聚合物与成膜性好的聚合物反应形成薄膜材料；
    2）在植入体主体所需修饰界面覆盖薄膜材料；
    3）在薄膜材料表面电沉积3,4-乙烯二氧噻吩得到所述植入体。
  8. 根据权利要求7所述的制备方法，其特征在于，具体包括以下步骤：
    a1）将富含阴离子的聚合物与成膜性好的聚合物进行混合，加热反应，得到液体薄膜材料；
    a2）在植入体主体所需修饰界面轻沾液体薄膜材料或者将液体薄膜材料均匀涂抹至植入体主体所需修饰界面，然后烘干，烘干后将其溶胀，溶胀过后重新烘干，得到所需修饰界面覆盖薄膜材料的植入体主体；
    a3）将所需修饰界面覆盖薄膜材料的植入体主体浸入3,4-乙烯二氧噻吩溶液中进行电沉积得到所述植入体；
    或b1）将富含阴离子的聚合物与成膜性好的聚合物进行混合，加热反应，得到液体薄膜材料；
    b2）先将液体薄膜材料均匀涂抹至玻片表面或适宜的模具中，然后烘干，烘干后再溶胀至薄膜脱落，之后剪取适宜大小的薄膜平铺至植入体主体所需修饰的界面，再重新烘干，得到所需修饰界面覆盖薄膜材料的植入体主体；
    b3）将所需修饰界面覆盖薄膜材料的植入体主体浸入3,4-乙烯二氧噻吩溶液中进行电沉积得到所述植入体。
  9. 根据权利要求8所述的制备方法，其特征在于，a1中所述加热反应的温度为80-95℃，所述加热反应的时间为12h以上；
    优选地，a2中所述烘干的温度为60-80℃，所述烘干的时间为6-12h；
    优选地，a2中所述重新烘干的的温度不得高于液体薄膜材料原材料的相变温度，所述重新烘干的时间为6-12h；
    优选地，a2中所述溶胀所用的溶剂为PBS溶液；
    优选地，a3中3,4-乙烯二氧噻吩溶液的浓度为1mM-25mM；
    优选地，a3中所述电沉积的工艺条件为电压0.6-2V，时间20-300s。
  10. 根据权利要求8所述的制备方法，其特征在于，b1中所述加热反应的温度为80-95℃，所述加热反应的时间为12h以上；
    优选地，b2中所述烘干的温度为60-80℃，所述烘干的时间为6-12h；
    优选地，b2中所述重新烘干的的温度不得高于液体薄膜材料原材料的相变温度，所述重新烘干的时间为6-12h；
    优选地，b2中所述溶胀所用的溶剂为PBS溶液；
    优选地，b3中3,4-乙烯二氧噻吩溶液的浓度为1mM-25mM；
    优选地，b3中所述电沉积的工艺条件为电压0.6-2V，时间20-300s。
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