A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo.
A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo.
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DOI：
10.1039/d3tb00710c
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发表时间：
2023-07
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影响因子：
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通讯作者：
Sizhe Huang;Sabrina Urbina Villafranca;Iyanah Mehta;Omri Yosfan;Eunji Hong;Anyang Wang;N. Wu;Qianbin Wang;Siyuan Rao
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文献类型：
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作者：
Sizhe Huang;Sabrina Urbina Villafranca;Iyanah Mehta;Omri Yosfan;Eunji Hong;Anyang Wang;N. Wu;Qianbin Wang;Siyuan Rao
具有自适应光学和机械特性的水凝胶在神经工程应用中显示出相当大的前景。然而，在生理条件下，随着时间的推移，水凝胶中未连接的无定形聚合物链会在吸水后引起体积膨胀。化学交联型聚乙烯醇(PVA)水凝胶具有抗疲劳特性和良好的生物相容性，可用于制造软神经探头。然而，PVA水凝胶基质的可能膨胀可能会影响基于水凝胶的生物电子学的结构稳定性及其在体内的长期功能。在这项研究中，我们利用原子层沉积(ALD)技术在化学交联的PVA水凝胶纤维上生成了无机二氧化硅(SiO_2)涂层。为了评价包覆SiO_2的PVA水凝胶纤维模拟体内环境的稳定性，我们进行了加速稳定性测试。与未包覆的纤维相比，包覆了二氧化硅的PVA水凝胶纤维在恶劣环境下一周的孵化期内表现出更好的稳定性，防止了膨胀，并保持了其机械和光学性能。这些包覆SiO_2的PVA水凝胶纤维具有纳米级的聚合物结晶结构域(6.5±0.1 nm)，弹性模量值为73.7±31.7 Mpa，最大伸长率为113.6±2 4.2%，光传输损耗最小(1.9±0.2 d B cm-1)。最后，我们将这些包覆了二氧化硅的PVA水凝胶纤维应用于体内，在运动行为测试中对转基因Thy1：：ChR2小鼠的运动皮质进行了光学激活。这组小鼠经过基因改造，表达了光敏离子通道-视紫红质-2(ChR2)，并被植入水凝胶纤维，将光传递到运动皮质区域(M2)。通过水凝胶纤维的光刺激导致光基因调制的小鼠运动行为，包括增加对侧旋转、移动速度和旅行距离。
Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality. In this study, we utilized an atomic layer deposition (ALD) technique to generate an inorganic, silicon dioxide (SiO2) coating layer on chemically cross-linked PVA hydrogel fibers. To evaluate the stability of SiO2-coated PVA hydrogel fibers mimicking the in vivo environment, we conducted accelerated stability tests. SiO2-coated PVA hydrogel fibers showed improved stability over a one-week incubation period under a harsh environment, preventing swelling and preserving their mechanical and optical properties compared to uncoated fibers. These SiO2-coated PVA hydrogel fibers demonstrated nanoscale polymeric crystalline domains (6.5 ± 0.1 nm), an elastic modulus of 73.7 ± 31.7 MPa, a maximum elongation of 113.6 ± 24.2%, and minimal light transmission loss (1.9 ± 0.2 dB cm-1). Lastly, we applied these SiO2-coated PVA hydrogel fibers in vivo to optically activate the motor cortex of transgenic Thy1::ChR2 mice during locomotor behavioral tests. This mouse cohort was genetically modified to express the light-sensitive ion channel, channelrhodopsin-2 (ChR2), and implanted with hydrogel fibers to deliver light to the motor cortex area (M2). Light stimulation via hydrogel fibers resulted in optogenetically modulated mouse locomotor behaviors, including increased contralateral rotation, mobility speeds, and travel distances.