Norris Sam C P, Tseng Peter, Kasko Andrea M
Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, 5121 Engineering V, Los Angeles, California 90095, United States.
California Nanosystems Institute, 570 Westwood Plaza, Los Angeles, California 90095, United States.
ACS Biomater Sci Eng. 2016 Aug 8;2(8):1309-1318. doi: 10.1021/acsbiomaterials.6b00237. Epub 2016 Jul 8.
Cell response to matrix mechanics is well-known; however, the ability to spatially pattern matrix stiffness to a high degree of control has been difficult to attain. This study describes the use of maskless photolithography as a flexible process for direct, noncontact gradient patterning of photodegradable hydrogels with custom graphics. Any input gray scale image can be used to directly chart hydrogel cross-link density as a function of spatial position. Hydrogels can be patterned with submicron resolution, with length scales within a single substrate spanning several orders of magnitude. A quantitative relationship between input grayscale image pixel intensity and output gel stiffness is validated, allowing for direct gradient patterning. Such physical gradient hydrogel constructs are rapidly produced in a highly controlled fashion with measured stiffness ranges and length scales that are physiologically relevant. Mesenchymal stem cells cultured on these physical gradients matrices congregate and align orthogonal to the gradient direction along iso-degraded lines. This approach results in a robust and high-throughput platform to answer key questions about cell response in heterogeneous physical environments.
细胞对基质力学的反应是众所周知的；然而，要在空间上高度精确地控制基质刚度一直难以实现。本研究描述了使用无掩模光刻作为一种灵活的工艺，用于对具有定制图形的可光降解水凝胶进行直接、非接触式梯度图案化。任何输入的灰度图像都可用于直接绘制水凝胶交联密度与空间位置的函数关系。水凝胶可以以亚微米分辨率进行图案化，单个基板内的长度尺度跨越几个数量级。验证了输入灰度图像像素强度与输出凝胶刚度之间的定量关系，从而实现直接梯度图案化。这种物理梯度水凝胶构建体以高度可控的方式快速生产，其测量的刚度范围和长度尺度与生理相关。在这些物理梯度基质上培养的间充质干细胞会沿着等降解线聚集并与梯度方向正交排列。这种方法产生了一个强大且高通量的平台，以回答关于细胞在异质物理环境中反应的关键问题。
