Hess Allison E, Potter Kelsey A, Tyler Dustin J, Zorman Christian A, Capadona Jeffrey R
Advanced Platform Technology Center, Rehabilitation Research and Development, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, USA.
J Vis Exp. 2013 Aug 20(78):e50078. doi: 10.3791/50078.
Implantable microdevices are gaining significant attention for several biomedical applications. Such devices have been made from a range of materials, each offering its own advantages and shortcomings. Most prominently, due to the microscale device dimensions, a high modulus is required to facilitate implantation into living tissue. Conversely, the stiffness of the device should match the surrounding tissue to minimize induced local strain. Therefore, we recently developed a new class of bio-inspired materials to meet these requirements by responding to environmental stimuli with a change in mechanical properties. Specifically, our poly(vinyl acetate)-based nanocomposite (PVAc-NC) displays a reduction in stiffness when exposed to water and elevated temperatures (e.g. body temperature). Unfortunately, few methods exist to quantify the stiffness of materials in vivo, and mechanical testing outside of the physiological environment often requires large samples inappropriate for implantation. Further, stimuli-responsive materials may quickly recover their initial stiffness after explantation. Therefore, we have developed a method by which the mechanical properties of implanted microsamples can be measured ex vivo, with simulated physiological conditions maintained using moisture and temperature control. To this end, a custom microtensile tester was designed to accommodate microscale samples with widely-varying Young's moduli (range of 10 MPa to 5 GPa). As our interests are in the application of PVAc-NC as a biologically-adaptable neural probe substrate, a tool capable of mechanical characterization of samples at the microscale was necessary. This tool was adapted to provide humidity and temperature control, which minimized sample drying and cooling. As a result, the mechanical characteristics of the explanted sample closely reflect those of the sample just prior to explantation. The overall goal of this method is to quantitatively assess the in vivo mechanical properties, specifically the Young's modulus, of stimuli-responsive, mechanically-adaptive polymer-based materials. This is accomplished by first establishing the environmental conditions that will minimize a change in sample mechanical properties after explantation without contributing to a reduction in stiffness independent of that resulting from implantation. Samples are then prepared for implantation, handling, and testing (Figure 1A). Each sample is implanted into the cerebral cortex of rats, which is represented here as an explanted rat brain, for a specified duration (Figure 1B). At this point, the sample is explanted and immediately loaded into the microtensile tester, and then subjected to tensile testing (Figure 1C). Subsequent data analysis provides insight into the mechanical behavior of these innovative materials in the environment of the cerebral cortex.
可植入微型设备在多种生物医学应用中受到了广泛关注。这类设备由多种材料制成,每种材料都有其自身的优缺点。最突出的是,由于设备尺寸为微观尺度,需要高模量以利于植入活体组织。相反,设备的硬度应与周围组织相匹配,以尽量减少局部应变。因此,我们最近开发了一类新型的仿生材料,通过在环境刺激下改变机械性能来满足这些要求。具体来说,我们的聚醋酸乙烯酯基纳米复合材料(PVAc-NC)在接触水和升高的温度(如体温)时会降低硬度。不幸的是,很少有方法能够在体内量化材料的硬度,而且在生理环境之外进行机械测试通常需要大尺寸样本,不适合用于植入。此外,刺激响应材料在取出后可能会迅速恢复其初始硬度。因此,我们开发了一种方法,通过使用湿度和温度控制来维持模拟生理条件,从而能够在体外测量植入的微样本的机械性能。为此,设计了一种定制的微拉伸试验机,以适应具有广泛杨氏模量范围(10兆帕至5吉帕)的微观尺度样本。由于我们的兴趣在于将PVAc-NC应用于具有生物适应性的神经探针基板,因此需要一种能够在微观尺度上对样本进行机械表征的工具。对该工具进行了改进,以提供湿度和温度控制,从而最大限度地减少样本干燥和冷却。结果,取出的样本的机械特性与取出前样本的机械特性密切相关。该方法的总体目标是定量评估刺激响应型、机械适应性聚合物基材料在体内的机械性能,特别是杨氏模量。这是通过首先确定环境条件来实现的,这些条件将使取出后样本机械性能的变化最小化,而不会导致与植入无关的硬度降低。然后将样本准备好用于植入、处理和测试(图1A)。每个样本被植入大鼠的大脑皮层,在此以取出的大鼠大脑表示,持续指定的时间(图1B)。此时,将样本取出并立即加载到微拉伸试验机中,然后进行拉伸测试(图1C)。后续的数据分析为这些创新材料在大脑皮层环境中的机械行为提供了深入了解。