Cancer Prevention Research Center, Shahroud University of Medical Sciences, Iran.
Bioengineering Center for Cancer, Department of Mechanical Engineering, Isfahan University of Technology, Iran.
J Biomater Appl. 2023 Aug;38(2):179-193. doi: 10.1177/08853282231182491. Epub 2023 Jun 26.
Extracellular matrix (ECM) is a dynamic and complex environment regulating the cell fate and behavior. It is characterized by biophysical and biochemical properties specific for each tissue. Interestingly, hydrogels can serve as exceptional artificial cellular microenvironments as they can be designed to mimic the key features of the native ECM. They are valuable tools to understand how cells respond to complex microenvironments in normal and pathologic conditions. However, unlike the highly dynamic structure of ECM, nearly all of the conventional hydrogel platforms are primarily static and lack the dynamic properties of native extracellular matrices. Thus, it is necessary to develop dynamic hydrogels to better understand the mechanisms by which dynamic changes of ECM contribute to biological processes. Stiffness is one of the significant dynamic components of ECM which must be appropriately mimicked over time . In this review, we cover recent advances in engineering strategies to make cell laden hydrogels with temporally tunable stiffness. We also highlight the applications of these hydrogel systems in biomedicine focusing on specific examples in cancer, cardiovascular system, tissue fibrosis and stem cell research. Finally, the challenges regarding the development and application of cell laden hydrogels with temporally tunable stiffness are proposed.
细胞外基质（ECM）是一个动态且复杂的环境，调节着细胞的命运和行为。它的特点是具有针对每种组织的独特生物物理和生化特性。有趣的是，水凝胶可以作为出色的人工细胞微环境，因为它们可以被设计成模仿天然 ECM 的关键特征。它们是了解细胞如何在正常和病理条件下对复杂微环境做出反应的有价值的工具。然而，与 ECM 高度动态的结构不同，几乎所有传统的水凝胶平台主要是静态的，缺乏天然细胞外基质的动态特性。因此，有必要开发动态水凝胶，以更好地理解 ECM 的动态变化如何促进生物过程。硬度是 ECM 的重要动态组成部分之一，必须随着时间的推移进行适当模拟。在本次综述中，我们将介绍用于制造具有时间可调硬度的细胞负载水凝胶的工程策略的最新进展。我们还强调了这些水凝胶系统在生物医学中的应用，重点介绍了癌症、心血管系统、组织纤维化和干细胞研究中的具体实例。最后，提出了具有时间可调硬度的细胞负载水凝胶的开发和应用所面临的挑战。
