Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 10, 20133 Milan, Italy.
Department of Agricultural and Environmental Sciences-Production, Landscape, Agroenergy and Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy.
Int J Mol Sci. 2021 Jan 15;22(2):830. doi: 10.3390/ijms22020830.
Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.
二维培养系统已经成为一个多世纪以来在体外研究细胞生物学最常用的方法。尽管它们提供了有用的信息,但这些系统可能会失去组织特异性的结构、生物力学效应器和来源于天然细胞外基质的生化线索,从而导致许多细胞功能和过程发生显著改变。值得注意的是,引入了能够在体外重现天然组织结构的三维(3D)平台,克服了其中的一些问题,因为它们更好地模拟了体内环境,并缩小了细胞培养环境与组织环境之间的差距。3D 培养系统目前广泛应用于癌症和干细胞生物学、药物测试和发现等研究领域。在这里,我们描述了细胞感知和响应生物力学线索的机制以及涉及的主要信号通路。我们提供了最新 3D 技术的总体视角。鉴于该主题的广泛性,我们集中讨论了水凝胶、生物反应器、3D 打印和生物打印、基于纳米纤维的支架以及脱细胞生物基质的制备的应用。此外,我们还报告了将 3D 培养与功能化纳米粒子结合使用的可能性,以获得用于纳米医学领域的高度预测性体外模型。