Single-Step Synthesis of Alginate Microgels Enveloped with a Covalent Polymeric Shell: A Simple Way to Protect Encapsulated Cells
Single-Step Synthesis of Alginate Microgels Enveloped with a Covalent Polymeric Shell: A Simple Way to Protect Encapsulated Cells
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一步合成共价聚合物壳包裹的藻酸盐微凝胶：保护封装细胞的简单方法
DOI：
10.1021/acsami.0c20613
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发表时间：
2021
影响因子：
9.5
通讯作者：
Raghavan, Srinivasa R.
中科院分区：
文献类型：
--
作者：
Ahn, So Hyun;Rath, Medha;Tsao, Chen-Yu;Bentley, William E.;Raghavan, Srinivasa R.
藻酸盐等生物聚合物微凝胶广泛用于封装细胞和其他生物有效负载。海藻酸盐是一种有吸引力的细胞封装材料，因为它无毒且方便：通过将海藻酸钠的水滴与二价阳离子（例如 Ca2+）接触，可以轻松形成球形海藻酸盐凝胶。凝胶中的藻酸盐链通过 Ca2+ 阳离子交联成 3-D 网络。然而，当将藻酸盐凝胶置于缓冲液中时，Ca2+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，封装的细胞被释放到外部溶液中。在这里，我们描述了上述问题的简单解决方案，其中涉及形成由共价交联凝胶的薄壳包裹的藻酸盐凝胶。壳是使用常规单体（例如丙烯酰胺（AAm）或丙烯酸酯衍生物，包括聚乙二醇二丙烯酸酯（PEGDA））通过自由基聚合形成的。整个过程在室温（或 37°C）温和的水性条件下一步完成。它涉及将藻酸盐溶液与自由基引发剂混合，然后将其以液滴形式引入含有 Ca2+ 和单体的储层中。经过简单的孵育或暴露于紫外线 (UV) 光的几分钟内，液滴就会转化为藻酸盐聚合物微胶囊，其核心为藻酸盐，外壳为聚合物（AAm 或 PEGDA）。微胶囊在机械上比传统的藻酸盐/Ca2+微凝胶更坚固，虽然后者在放入缓冲液或柠檬酸钠等螯合剂中时会膨胀和降解，但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封装在这些微胶囊中，发现这些细胞随着时间的推移仍然保持活力和功能。最后，合成技术的一种变化被证明可以生成多层微胶囊，其液体核心被海藻酸盐和 AAm 凝胶的同心层包围。我们预计这里提出的方法将在细胞疗法、人造细胞、药物输送和组织工程等多个领域得到应用。
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 Ca2+. Alginate chains in the gel become cross-linked by Ca2+cations into a 3-D network. When alginate gels are placed in a buffer, however, the Ca2+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 athin shell of a covalently cross-linked gel. 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 Ca2+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/Ca2+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 generatemultilayeredmicrocapsules 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.