Urciuolo F, Imparato G, Netti P A
Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy.
Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, Naples, Italy.
Front Bioeng Biotechnol. 2023 Jun 26;11:1197075. doi: 10.3389/fbioe.2023.1197075. eCollection 2023.
The extracellular microenvironment regulates cell decisions through the accurate presentation at the cell surface of a complex array of biochemical and biophysical signals that are mediated by the structure and composition of the extracellular matrix (ECM). On the one hand, the cells actively remodel the ECM, which on the other hand affects cell functions. This cell-ECM dynamic reciprocity is central in regulating and controlling morphogenetic and histogenetic processes. Misregulation within the extracellular space can cause aberrant bidirectional interactions between cells and ECM, resulting in dysfunctional tissues and pathological states. Therefore, tissue engineering approaches, aiming at reproducing organs and tissues , should realistically recapitulate the native cell-microenvironment crosstalk that is central for the correct functionality of tissue-engineered constructs. In this review, we will describe the most updated bioengineering approaches to recapitulate the native cell microenvironment and reproduce functional tissues and organs . We have highlighted the limitations of the use of exogenous scaffolds in recapitulating the regulatory/instructive and signal repository role of the native cell microenvironment. By contrast, strategies to reproduce human tissues and organs by inducing cells to synthetize their own ECM acting as a provisional scaffold to control and guide further tissue development and maturation hold the potential to allow the engineering of fully functional histologically competent three-dimensional (3D) tissues.
细胞外微环境通过细胞表面精确呈现由细胞外基质（ECM）的结构和组成介导的一系列复杂生化和生物物理信号来调节细胞决策。一方面，细胞积极重塑ECM，另一方面，ECM影响细胞功能。这种细胞与ECM的动态相互作用是调节和控制形态发生和组织发生过程的核心。细胞外空间的调节异常会导致细胞与ECM之间异常的双向相互作用，从而导致组织功能失调和病理状态。因此，旨在再生器官和组织的组织工程方法应切实模拟天然细胞与微环境的相互作用，这对于组织工程构建体的正确功能至关重要。在本综述中，我们将描述最新的生物工程方法，以模拟天然细胞微环境并再生功能性组织和器官。我们强调了在模拟天然细胞微环境的调节/指导和信号储存作用时使用外源性支架的局限性。相比之下，通过诱导细胞合成自身的ECM作为临时支架来控制和引导进一步的组织发育和成熟，从而再生人体组织和器官的策略，有可能实现功能完全正常、组织学上合格的三维（3D）组织工程。
