Department of Chemical & Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, United States.
Department of Chemistry & Biochemistry, University of Maryland, College Park, Maryland 20742, United States.
ACS Appl Mater Interfaces. 2021 Apr 28;13(16):18432-18442. doi: 10.1021/acsami.0c20613. Epub 2021 Apr 19.
Microgels of biopolymers such as alginate are widely used to encapsulate cells and other biological payloads. Alginate is an attractive material for cell encapsulation because it is nontoxic and convenient: spherical alginate gels are easily created by contacting aqueous droplets of sodium alginate with divalent cations such as Ca. Alginate chains in the gel become cross-linked by Ca cations into a 3-D network. When alginate gels are placed in a buffer, however, the Ca cross-links are eliminated by exchange with Na, thereby weakening and degrading the gels. With time, encapsulated cells are released into the external solution. Here, we describe a simple solution to the above problem, which involves forming alginate gels enveloped by a . The shell is formed via free-radical polymerization using conventional monomers such as acrylamide (AAm) or acrylate derivatives, including polyethylene glycol diacrylate (PEGDA). The entire process is performed in a single step at room temperature (or 37 °C) under mild, aqueous conditions. It involves combining the alginate solution with a radical initiator, which is then introduced as droplets into a reservoir containing Ca and monomers. Within minutes of either simple incubation or exposure to ultraviolet (UV) light, the droplets are converted into alginate-polymer microcapsules with a core of alginate and a shell of the polymer (AAm or PEGDA). The microcapsules are mechanically more robust than conventional alginate/Ca microgels, and while the latter swell and degrade when placed in buffers or in chelators like sodium citrate, the former remain stable under all conditions. We encapsulate both bacteria and mammalian cells in these microcapsules and find that the cells remain viable and functional over time. Lastly, a variation of the synthesis technique is shown to generate microcapsules with a liquid core surrounded by concentric layers of alginate and AAm gels. We anticipate that the approaches presented here will find application in a variety of areas including cell therapies, artificial cells, drug delivery, and tissue engineering.
生物聚合物（如海藻酸盐）的微凝胶被广泛用于包裹细胞和其他生物有效载荷。海藻酸盐是一种用于细胞包裹的有吸引力的材料，因为它是无毒且方便的：通过将海藻酸钠的水性液滴滴加到二价阳离子（如 Ca）中，很容易形成球形海藻酸盐凝胶。凝胶中的海藻酸盐链通过 Ca 阳离子交联成 3D 网络。然而，当海藻酸盐凝胶被放置在缓冲液中时，Ca 交联通过与 Na 交换而被消除，从而削弱和降解凝胶。随着时间的推移，包裹的细胞被释放到外部溶液中。在这里，我们描述了一个简单的解决方案，涉及形成由 包裹的海藻酸盐凝胶。壳是通过使用常规单体（如丙烯酰胺（AAm）或丙烯酸酯衍生物，包括聚乙二醇二丙烯酸酯（PEGDA））的自由基聚合形成的。整个过程在室温（或 37°C）下在温和的水性条件下在单个步骤中进行。它涉及将海藻酸盐溶液与自由基引发剂混合，然后将其作为液滴滴入含有 Ca 和单体的储液器中。在简单孵育或暴露于紫外（UV）光的几分钟内，液滴就会转化为具有海藻酸盐核心和聚合物（AAm 或 PEGDA）壳的海藻酸盐-聚合物微胶囊。与传统的海藻酸盐/Ca 微凝胶相比，微胶囊具有更强的机械稳定性，并且后者在缓冲液或柠檬酸钠等螯合剂中会膨胀和降解，而前者在所有条件下都保持稳定。我们将细菌和哺乳动物细胞包裹在这些微胶囊中，并发现随着时间的推移，细胞保持存活和功能。最后，展示了合成技术的变体，用于生成具有液体核心的 微胶囊，该核心被海藻酸盐和 AAm 凝胶的同心层包围。我们预计这里提出的方法将在包括细胞治疗、人工细胞、药物输送和组织工程在内的各种领域得到应用。
