Peptide Hydrogels - Versatile Matrices for 3D Cell Culture in Cancer Medicine.

Peptide Hydrogels - Versatile Matrices for 3D Cell Culture in Cancer Medicine.
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DOI:
10.3389/fonc.2015.00092
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发表时间:
2015
影响因子:
4.7
通讯作者:
Langhans SA
Langhans SA
中科院分区:
医学3区
文献类型:
--
作者:
Worthington P;Pochan DJ;Langhans SA

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传统的二维 (2D) 细胞培养系统对我们对癌症生物学的理解做出了巨大贡献,但在模拟肿瘤微环境等体内条件方面存在显着局限性。在体外,三维 (3D) 细胞培养模型代表了简化的 2D 培养模型与复杂且昂贵的体内模型之间更准确的中间平台。 3D体外模型可以克服由于营养物质供应过剩、细胞与细胞以及细胞与材料之间的非生理相互作用引起的2D体外限制,并允许细胞、基质和细胞外基质之间的动态相互作用。此外,3D 培养允许形成浓度梯度,包括氧气、代谢物和生长因子,化学梯度在许多细胞功能中发挥着不可或缺的作用,包括正常上皮细胞和体内癌症环境中的发育到信号传导。目前,3D 培养最常用的基质是生物衍生材料,例如基质胶和胶原蛋白。然而,近年来,更明确的合成材料已成为 3D 培养的支架,其优点是形成明确的、设计的、可调节的材料,以控制基质电荷、刚度、孔隙率、纳米结构、可降解性和粘附特性,以及其他材料和生物特性。目前可用于 3D 细胞培养的合成材料的一个重要领域是短序列、自组装肽水凝胶。除了回顾最近在材料、结构和机械性能控制方面的工作外,我们还将讨论肽水凝胶的生化功能化,以及这种功能化与所需的水凝胶材料特性相结合如何影响 3D 培养中的肿瘤细胞行为。
Traditional two-dimensional (2D) cell culture systems have contributed tremendously to our understanding of cancer biology but have significant limitations in mimicking in vivo conditions such as the tumor microenvironment. In vitro, three-dimensional (3D) cell culture models represent a more accurate, intermediate platform between simplified 2D culture models and complex and expensive in vivo models. 3D in vitro models can overcome 2D in vitro limitations caused by the oversupply of nutrients, and unphysiological cell–cell and cell–material interactions, and allow for dynamic interactions between cells, stroma, and extracellular matrix. In addition, 3D cultures allow for the development of concentration gradients, including oxygen, metabolites, and growth factors, with chemical gradients playing an integral role in many cellular functions ranging from development to signaling in normal epithelia and cancer environments in vivo. Currently, the most common matrices used for 3D culture are biologically derived materials such as matrigel and collagen. However, in recent years, more defined, synthetic materials have become available as scaffolds for 3D culture with the advantage of forming well-defined, designed, tunable materials to control matrix charge, stiffness, porosity, nanostructure, degradability, and adhesion properties, in addition to other material and biological properties. One important area of synthetic materials currently available for 3D cell culture is short sequence, self-assembling peptide hydrogels. In addition to the review of recent work toward the control of material, structure, and mechanical properties, we will also discuss the biochemical functionalization of peptide hydrogels and how this functionalization, coupled with desired hydrogel material characteristics, affects tumor cell behavior in 3D culture.
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