Complementary, Semiautomated Methods for Creating Multidimensional PEG-Based Biomaterials
Complementary, Semiautomated Methods for Creating Multidimensional PEG-Based Biomaterials
复制标题
DOI：
10.1021/acsbiomaterials.7b00737
复制
发表时间：
2018-02-01
影响因子：
5.8
通讯作者：
Peyton, Shelly R.
中科院分区：
文献类型：
--
作者：
Brooks, Elizabeth A.;Jansen, Lauren E.;Peyton, Shelly R.
模拟细胞外基质（ECM）的选定特征（如其刚度，蛋白质组成和维度）的可调生物材料越来越受欢迎，用于研究细胞如何感知和响应ECM信号。在该领域中，这些生物材料如何复杂和如何良好地代表体内微环境与它们如何容易制造以及它们如何适应自动化制造技术之间存在着重大的权衡。为了解决这一需要，将更复杂的生物材料设计与高通量筛选方法相结合，我们提出了几种在96孔板中制造合成生物材料的方法，并证明它们可以适用于半自动液体处理机器人。这些平台包括（1）具有共价连接的ECM蛋白的玻璃底板和（2）具有可调刚度和蛋白质组成的水凝胶，其中细胞接种在表面上或（3）装载在三维水凝胶基质内。这项研究包括概念验证结果，证明了通过这些ECM线索以半自动方式控制乳腺癌细胞系表型。我们预见使用这些方法作为一种机制，以弥合高通量细胞基质筛选和工程ECM模拟生物材料之间的差距。
Tunable biomaterials that mimic selected features of the extracellular matrix (ECM) such as its stiffness, protein composition, and dimensionality are increasingly popular for studying how cells sense and respond to ECM cues. In the field, there exists a significant trade-off for how complex and how well these biomaterials represent the in vivo microenvironment versus how easy they are to make and how adaptable they are to automated fabrication techniques. To address this need to integrate more complex biomaterials design with high-throughput screening approaches, we present several methods to fabricate synthetic biomaterials in 96-well plates and demonstrate that they can be adapted to semiautomated liquid handling robotics. These platforms include (1) glass bottom plates with covalently attached ECM proteins and (2) hydrogels with tunable stiffness and protein composition with either cells seeded on the surface or (3) laden within the three-dimensional hydrogel matrix. This study includes proof-of-concept results demonstrating control over breast cancer cell line phenotypes via these ECM cues in a semiautomated fashion. We foresee the use of these methods as a mechanism to bridge the gap between high-throughput cell-matrix screening and engineered ECM-mimicking biomaterials.