Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
Diamantina Institute, The University of Queensland, St Lucia, QLD 4072, Australia.
Biomater Adv. 2022 May;136:212782. doi: 10.1016/j.bioadv.2022.212782. Epub 2022 Mar 30.
The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random. This study systematically evaluates the biophysical attributes of three widely used natural hydrogels (Matrigel, collagen gel and agarose gel) including complex modulus, loss tangent, diffusive permeability and pore size. A new and facile method was developed combining Critical Point Drying, Scanning Electron Microscopy imaging and a MATLAB image processing program (CSM method) for the characterization of hydrogel microstructures. This CSM method allows accurate measurement of the hydrogel pore size down to nanometer resolution. Furthermore, a microfluidic device was implemented to measure the hydrogel permeability (P) as a function of particle size and gel concentration. Among the three gels, collagen gel has the lowest complex modulus, medium pore size, and the highest loss tangent. Agarose gel exhibits the highest complex modulus, the lowest loss tangent and the smallest pore size. Collagen gel and Matrigel produced complex moduli close to that estimated for cancer ECM. The P of these hydrogels decreases significantly with the increase of particle size. By assessing different hydrogels' biophysical characteristics, this study provides valuable insights for tailoring their properties for various three-dimensional cancer models.
细胞外基质 (ECM) 是肿瘤微环境的重要组成部分。它在调节细胞-细胞和细胞-基质相互作用方面起着关键作用。然而，对于不同广泛使用的 ECM 模拟水凝胶及其性质缺乏系统和比较研究，使得选择适合模拟不同体内条件的水凝胶变得非常随机。本研究系统评估了三种广泛使用的天然水凝胶（Matrigel、胶原凝胶和琼脂糖凝胶）的生物物理特性，包括复合模量、损耗角正切、扩散渗透性和孔径。开发了一种新的简便方法，结合临界点干燥、扫描电子显微镜成像和 MATLAB 图像处理程序（CSM 方法）来表征水凝胶的微观结构。这种 CSM 方法允许以纳米分辨率准确测量水凝胶的孔径。此外，还实施了微流控装置来测量水凝胶的渗透性 (P) 作为粒径和凝胶浓度的函数。在这三种凝胶中，胶原凝胶的复合模量最低、孔径中等、损耗角正切最高。琼脂糖凝胶表现出最高的复合模量、最低的损耗角正切和最小的孔径。胶原凝胶和 Matrigel 的复合模量接近估计的癌症 ECM。这些水凝胶的 P 随着粒径的增加而显著降低。通过评估不同水凝胶的生物物理特性，本研究为针对各种三维癌症模型定制其特性提供了有价值的见解。
