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Cell armor for protection against environmental stress: Advances, challenges and applications in micro- and nanoencapsulation of mammalian cells.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2018-11-24 , DOI: 10.1016/j.actbio.2018.11.040
Onur Hasturk 1 , David L Kaplan 1
Affiliation  

Unlike unicellular organisms and plant cells surrounded with a cell wall, naked plasma membranes of mammalian cells make them more susceptible to environmental stresses encountered during in vitro biofabrication and in vivo cell therapy applications. Recent advances in micro- and nanoencapsulation of single mammalian cells provide an effective strategy to isolate cells from their surroundings and protect them against harsh environmental conditions. Microemulsification and droplet-based microfluidics have enabled researchers to encapsulate single cells within a variety of microscale hydrogel materials with a range of biochemical and mechanical properties and functionalities including enhanced cell-matrix interactions or on-demand degradation. In addition to microcapsules, nanocoatings of various organic and inorganic substances on mammalian cells have allowed for the formation of protective shells. A wide range of synthetic and natural polymers, minerals and supramolecular metal-organic complexes have been deposited as nanolayers on the cells via electrostatic interactions, receptor-ligand binding, non-specific interactions, and in situ polymerization/crosslinking. Here, current strategies in encapsulation of single mammalian cells along with challenges and advances are reviewed. Protection of encapsulated stem cells, fibroblasts, red and white blood cells and cancer cells against harsh in vitro and in vivo conditions including anoikis, UV radiation, physical forces, proteolytic enzymes and immune clearance are discussed. STATEMENT OF SIGNIFICANCE: The mechanical fragility of the plasma membrane and susceptibility to extracellular biochemical factors due to the lack of a physical barrier like a tough cell wall or exoskeleton make mammalian cells extra sensitive to harsh environmental conditions. This sensitively, in turn, limits the ex vivo storage, handling and manipulation of mammalian cells, as well as their in vivo applications. Environmental stresses such as exposure to UV, reactive chemicals and mechanical stress during biofabrication processes like 3D bioprinting can often compromise cell viability and function. Micro- and nanoencapsulation of single mammalian cells in protective shells have emerged as promising approaches to isolate cells from their surroundings and enhance resistance against perturbations in conditions during regenerative medicine and tissue engineering applications. In this review, the current state of art of single cell encapsulation strategies and the challenges associated with these technologies are discussed in detail. This is followed by the review of the protection provided by cell armor against a range of harsh in vitro and in vivo conditions.

中文翻译:


用于抵御环境压力的细胞装甲:哺乳动物细胞微米和纳米封装的进展、挑战和应用。



与被细胞壁包围的单细胞生物和植物细胞不同,哺乳动物细胞的裸露质膜使它们更容易受到体外生物制造和体内细胞治疗应用过程中遇到的环境压力的影响。单个哺乳动物细胞的微米和纳米封装的最新进展提供了一种有效的策略,将细胞与周围环境隔离并保护它们免受恶劣环境条件的影响。微乳化和基于液滴的微流体使研究人员能够将单细胞封装在各种微型水凝胶材料中,这些材料具有一系列生化和机械特性和功能,包括增强的细胞-基质相互作用或按需降解。除了微胶囊之外,哺乳动物细胞上的各种有机和无机物质的纳米涂层也可以形成保护壳。多种合成和天然聚合物、矿物质和超分子金属有机复合物已通过静电相互作用、受体-配体结合、非特异性相互作用和原位聚合/交联以纳米层形式沉积在细胞上。在此,回顾了当前封装单个哺乳动物细胞的策略以及挑战和进展。讨论了保护封装的干细胞、成纤维细胞、红细胞、白细胞和癌细胞免受恶劣的体外和体内条件(包括失巢凋亡、紫外线辐射、物理力、蛋白水解酶和免疫清除)的影响。 意义陈述:由于缺乏坚韧的细胞壁或外骨骼等物理屏障,质膜的机械脆弱性和对细胞外生化因素的敏感性使哺乳动物细胞对恶劣的环境条件格外敏感。这反过来又敏感地限制了哺乳动物细胞的离体储存、处理和操作,以及它们的体内应用。 3D 生物打印等生物制造过程中的环境压力(例如暴露于紫外线、反应性化学物质和机械压力)通常会损害细胞活力和功能。将单个哺乳动物细胞封装在保护壳中已成为将细胞与周围环境隔离并增强再生医学和组织工程应用中的抗干扰能力的有前途的方法。在这篇综述中,详细讨论了单细胞封装策略的最新技术以及与这些技术相关的挑战。随后审查了细胞装甲针对一系列恶劣的体外和体内条件提供的保护。
更新日期:2019-08-28
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