Cimmino Chiara, Rossano Lucia, Netti Paolo Antonio, Ventre Maurizio
Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy.
Center for Advanced Biomaterials for Healthcare@CRIB, Fondazione Istituto Italiano di Tecnologia, Naples, Italy.
Front Bioeng Biotechnol. 2018 Dec 4;6:190. doi: 10.3389/fbioe.2018.00190. eCollection 2018.
Biophysical and biochemical signals of material surfaces potently regulate cell functions and fate. In particular, micro- and nano-scale patterns of adhesion signals can finely elicit and affect a plethora of signaling pathways ultimately affecting gene expression, in a process known as mechanotransduction. Our fundamental understanding of cell-material signals interaction and reaction is based on static culturing platforms, i.e., substrates exhibiting signals whose configuration is time-invariant. However, cells are exposed to arrays of biophysical and biochemical signals that change in time and space and the way cells integrate these might eventually dictate their behavior. Advancements in fabrication technologies and materials engineering, have recently enabled the development of culturing platforms able to display patterns of biochemical and biophysical signals whose features change in time and space in response to external stimuli and according to selected programmes. These dynamic devices proved to be particularly helpful in shedding light on how cells adapt to a dynamic microenvironment or integrate spatio-temporal variations of signals. In this work, we present the most relevant findings in the context of dynamic platforms for controlling cell functions and fate . We place emphasis on the technological aspects concerning the fabrication of platforms displaying micro- and nano-scale dynamic signals and on the physical-chemical stimuli necessary to actuate the spatio-temporal changes of the signal patterns. In particular, we illustrate strategies to encode material surfaces with dynamic ligands and patterns thereof, topographic relieves and mechanical properties. Additionally, we present the most effective, yet cytocompatible methods to actuate the spatio-temporal changes of the signals. We focus on cell reaction and response to dynamic changes of signal presentation. Finally, potential applications of this new generation of culturing systems for and applications, including regenerative medicine and cell conditioning are presented.
材料表面的生物物理和生化信号可有效调节细胞功能和命运。特别是，粘附信号的微米和纳米级模式能够精确引发并影响大量信号通路，最终影响基因表达，这一过程称为机械转导。我们对细胞与材料信号相互作用及反应的基本理解基于静态培养平台，即展示信号配置不随时间变化的底物。然而，细胞会接触到在时间和空间上变化的生物物理和生化信号阵列，而细胞整合这些信号的方式最终可能决定其行为。制造技术和材料工程的进步，最近使得能够开发出培养平台，这些平台能够展示生化和生物物理信号模式，其特征会根据外部刺激并按照选定程序在时间和空间上发生变化。这些动态装置被证明在揭示细胞如何适应动态微环境或整合信号的时空变化方面特别有帮助。在这项工作中，我们展示了在用于控制细胞功能和命运的动态平台背景下的最相关发现。我们强调了与制造展示微米和纳米级动态信号的平台相关的技术方面，以及激活信号模式时空变化所需的物理化学刺激。特别是，我们阐述了用动态配体及其模式、地形起伏和机械性能对材料表面进行编码的策略。此外，我们介绍了激活信号时空变化的最有效且细胞相容的方法。我们关注细胞对信号呈现动态变化的反应和响应。最后，展示了这种新一代培养系统在再生医学和细胞调节等应用中的潜在应用。
