ARC Centre of Excellence for Electromaterials Science, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122, Australia.
The Aikenhead Centre for Medical Discovery, St Vincent's Hospital Melbourne, Melbourne, Victoria 3065, Australia.
ACS Biomater Sci Eng. 2021 Jun 14;7(6):2279-2295. doi: 10.1021/acsbiomaterials.0c01734. Epub 2021 May 6.
The human tissues most sensitive to electrical activity such as neural and muscle tissues are relatively soft, and yet traditional conductive materials used to interface with them are typically stiffer by many orders of magnitude. Overcoming this mismatch, by creating both very soft and electroactive materials, is a major challenge in bioelectronics and biomaterials science. One strategy is to imbue soft materials, such as hydrogels, with electroactive properties by adding small amounts of highly conductive nanomaterials. However, electroactive hydrogels reported to date have required relatively large volume fractions (>1%) of added nanomaterial, have shown only modest electroactivity, and have not been processable via additive manufacturing to create 3D architectures. Here, we describe the development and characterization of improved biocompatible photo-cross-linkable soft hybrid electroactive hydrogels based on gelatin methacryloyol (GelMA) and large area graphene oxide (GO) flakes, which resolve each of these three limitations. The addition of very small amounts (less than a 0.07% volume fraction) of GO to a 5% w/v GelMA hydrogel resulted in a dramatic (∼35-fold) decrease in the impedance at 1 Hz compared with GelMA alone. The GelMA/GO coated indium tin oxide (ITO) electrode also showed a considerable reduction in the impedance at 1 kHz (down to 170 Ω compared with 340 Ω for the GelMA-coated ITO), while charge injection capacity increased more than 6-fold. We attribute this enhanced electroactivity to the increased electroactive surface area contributed by the GO. Despite this dramatic change in electroactivity, the GelMA/GO composite hydrogels' mechanical properties were only moderately affected. Mechanical properties increased by ∼2-fold, and therefore, the hydrogels' desired softness of <4 kPa was retained. Also, we demonstrate how light attenuation through the gel can be used to create a stiffness gradient with the exposed surface of the gel having an elastic modulus of <1.5 kPa. GO addition also enhanced the rheological properties of the GelMA composites, thus facilitating 3D extrusion printing. GelMA/GO enhanced filament formation as well as improved printability and the shape fidelity/integrity of 3D printed structures compared with GelMA alone. Additionally, the GelMA/GO 3D printed structures presented a higher electroactive behavior than nonprinted samples containing the same GelMA/GO amount, which can be attributed to the higher electroactive surface area of 3D printed structures. These findings provide new rational choices of electroactive hydrogel (EAH) compositions with broad potential applications in bioelectronics, tissue engineering, and drug delivery.
人体组织中对电活动最敏感的组织，如神经和肌肉组织，相对柔软，但用于与之接口的传统导电材料的柔韧性通常要低好几个数量级。克服这种不匹配，通过创造既非常柔软又具有电活性的材料，是生物电子学和生物材料科学的一个主要挑战。一种策略是通过添加少量高导电性的纳米材料，使软材料（如水凝胶）具有电活性。然而，迄今为止报道的具有电活性的水凝胶需要相对较大的纳米材料添加体积分数（>1%），仅表现出适度的电活性，并且不能通过增材制造来创建 3D 结构。在这里，我们描述了基于明胶甲基丙烯酰基（GelMA）和大面积氧化石墨烯（GO）薄片的改进的生物相容性光交联软混合电活性水凝胶的开发和表征，该水凝胶解决了这三个限制中的每一个。与单独的 GelMA 相比，将非常少量（小于 0.07%体积分数）的 GO 添加到 5%w/v GelMA 水凝胶中，导致在 1 Hz 时的阻抗急剧降低（降低了约 35 倍）。涂有 GelMA/GO 的铟锡氧化物（ITO）电极在 1 kHz 时的阻抗也显著降低（从涂有 GelMA 的 ITO 的 340 Ω降至 170 Ω），同时注入容量增加了 6 倍以上。我们将这种增强的电活性归因于 GO 增加的电活性表面积。尽管电活性发生了这种剧烈变化，但 GelMA/GO 复合水凝胶的机械性能仅受到适度影响。机械性能提高了约 2 倍，因此保留了水凝胶<4 kPa 的所需柔软度。此外，我们展示了如何通过凝胶的光衰减来创建具有凝胶暴露表面的弹性模量<1.5 kPa 的刚度梯度。GO 的添加还增强了 GelMA 复合材料的流变性能，从而促进了 3D 挤出打印。与单独的 GelMA 相比，GelMA/GO 增强了长丝的形成以及打印的可操作性和 3D 打印结构的形状保真度/完整性。此外，与含有相同 GelMA/GO 量的非打印样品相比，GelMA/GO 3D 打印结构表现出更高的电活性行为，这归因于 3D 打印结构更高的电活性表面积。这些发现为具有广泛生物电子学、组织工程和药物输送应用潜力的电活性水凝胶（EAH）组成提供了新的合理选择。
