Worthington Peter, Pochan Darrin J, Langhans Sigrid A
Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children , Wilmington, DE , USA ; Department of Biomedical Engineering, Delaware Biotechnology Institute, University of Delaware , Newark, DE , USA.
Department of Materials Science and Engineering, Delaware Biotechnology Institute, University of Delaware , Newark, DE , USA.
Front Oncol. 2015 Apr 20;5:92. doi: 10.3389/fonc.2015.00092. eCollection 2015.
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.
传统的二维（2D）细胞培养系统极大地促进了我们对癌症生物学的理解，但在模拟体内条件（如肿瘤微环境）方面存在显著局限性。在体外，三维（3D）细胞培养模型代表了一个更准确的中间平台，介于简化的2D培养模型和复杂且昂贵的体内模型之间。3D体外模型可以克服由于营养物质供应过多、非生理性的细胞-细胞和细胞-材料相互作用导致的2D体外局限性，并允许细胞、基质和细胞外基质之间进行动态相互作用。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，化学梯度在从发育到体内正常上皮和癌症环境中的信号传导等许多细胞功能中起着不可或缺的作用。目前，用于3D培养的最常见基质是生物衍生材料，如基质胶和胶原蛋白。然而，近年来，更明确的合成材料已作为3D培养的支架可用，其优点是形成定义明确、设计合理、可调节的材料，以控制基质电荷、硬度、孔隙率、纳米结构、降解性和粘附特性，以及其他材料和生物学特性。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。除了回顾最近在控制材料、结构和机械性能方面的工作外，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。
