Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca la Peraleda s/n, 45071 Toledo, Spain.
Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca la Peraleda s/n, 45071 Toledo, Spain.
Acta Biomater. 2019 May;90:71-86. doi: 10.1016/j.actbio.2019.03.037. Epub 2019 Mar 21.
Intraspinal microstimulation (ISMS) may help to restore motor functions after spinal cord injury. ISMS caudal to the lesion activates motoneurons and evokes selective movements with graded force in rats and other mammals. We investigated the safety and effectiveness of conducting polymer (CP)-coated carbon microfibers (CMFs) for ISMS. 7-µm-diameter CMFs coated with poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] (PEDOT:PSS-co-MA) were used to apply current-controlled biphasic electric pulses at the cervical spinal cord (C7) of anesthetized rats. Electrode performance and motoneuron activation, as readout by voltage transients, cyclic voltammetry, electrochemical impedance spectroscopy, electromyography (EMG) and foreleg kinematics, were investigated as a function of microfiber length (50 µm vs. 250 µm) and presence of polymer coating. The microfibers were very effective in activating specific spinal motoneurons, with the lowest stimulus thresholds varying between -28 µA and -46 µA in the cathodic phase. EMG and kinematic thresholds decreased when the microfiber tip approached the targeted motor nucleus (triceps brachii, t.b.) from the dorsal spinal cord surface. ISMS with polymer-coated CMFs produced higher electrical activity in the t.b. fascicles compared to bare CMFs. PEDOT:PSS-co-MA coating of 250-µm CMFs avoided the generation of unsafe overvoltages for biphasic pulses up to -80/+40 µA in vivo, although the positive effect of the conducting polymer was lost after the application of a few thousands of electric pulses. Thus, CP-coated CMFs may provide an effective and minimally invasive electrode for ISMS; however, polymer optimization is still required to improve its electrical stability and safety for long-term use. Statement of significance Intraspinal microstimulation may restore motor functions after spinal cord injury. In the present study we demonstrate that carbon microfibers (CMFs) coated with the conducting polymer PEDOT:PSS-co-MA can be advantageously used for this purpose. These microfibers allow for both effective and temporarily safe electrical activation of spinal motor circuits with high spatial resolution. The presence of the polymer enhances the effectiveness of the electrical stimuli to recruit spinal motoneurons. Thus, conducting polymer-coated CMFs have potential for the development of advanced neuroprosthetic devices, although further improvements are needed regarding their electrochemical and mechanical stability.
脊髓内微刺激 (ISMS) 可能有助于恢复脊髓损伤后的运动功能。在损伤以下部位进行 ISMS 可以激活运动神经元，并在大鼠和其他哺乳动物中引发具有分级力的选择性运动。我们研究了涂有导电聚合物 (CP) 的碳微纤维 (CMF) 用于 ISMS 的安全性和有效性。使用直径为 7 µm 的涂有聚(3,4-亚乙基二氧噻吩)掺杂聚[(4-苯乙烯磺酸)-共-(马来酸)] (PEDOT:PSS-co-MA) 的 CMF 施加电流控制双相电脉冲在麻醉大鼠的颈脊髓 (C7)。通过电压瞬变、循环伏安法、电化学阻抗谱、肌电图 (EMG) 和前肢运动学来研究微纤维长度 (50 µm 与 250 µm) 和聚合物涂层存在对电极性能和运动神经元激活的影响。微纤维非常有效地激活特定的脊髓运动神经元，最低刺激阈值在阴极相在-28 µA 到-46 µA 之间变化。当微纤维尖端从脊髓背表面接近目标运动核（肱三头肌，t.b.）时，EMG 和运动学阈值降低。与裸 CMF 相比，聚合物涂覆的 CMF 进行 ISMS 可在 t.b.束中产生更高的电活动。250 µm CMF 的 PEDOT:PSS-co-MA 涂层避免了体内高达-80/+40 µA 的双相脉冲产生不安全的过电压，尽管在施加几千次电脉冲后，导电聚合物的积极作用消失了。因此，CP 涂覆的 CMF 可为 ISMS 提供有效且微创的电极；然而，仍需要对聚合物进行优化以提高其电稳定性和长期使用的安全性。意义声明 脊髓内微刺激可能在脊髓损伤后恢复运动功能。在本研究中，我们证明了涂有导电聚合物 PEDOT:PSS-co-MA 的碳微纤维 (CMF) 可为此目的提供优势。这些微纤维允许以高空间分辨率对脊髓运动回路进行有效且暂时安全的电激活。聚合物的存在增强了募集脊髓运动神经元的电刺激的有效性。因此，导电聚合物涂覆的 CMF 具有开发先进神经假体装置的潜力，尽管需要进一步改进其电化学和机械稳定性。
