Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry
Versatile click alginate hydrogels crosslinked via tetrazine-norbornene chemistry
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DOI：
10.1016/j.biomaterials.2015.01.048
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发表时间：
2015-05-01
期刊：
影响因子：
14
通讯作者：
Joshi, Neel S.
中科院分区：
文献类型：
--
作者：
Desai, Rajiv M.;Koshy, Sandeep T.;Joshi, Neel S.
海藻酸盐水凝胶是一种特性良好的生物惰性材料，在许多生物医学应用中用于输送药物、蛋白质和细胞。不幸的是，典型的共价交联藻酸盐水凝胶是使用化学策略形成的，由于缺乏化学选择性，可能对生物有害。在这项工作中，我们将四嗪和降冰片烯基团引入藻酸盐聚合物链，随后形成共价交联的点击藻酸盐水凝胶，能够封装细胞而不损伤细胞。快速、生物正交和特异性的点击反应是不可逆的，并且可以轻松掺入具有高封装后活力的细胞。点击藻酸盐水凝胶的溶胀和机械性能可以通过总聚合物浓度和互补点击官能团的化学计量比来调节。点击藻酸盐水凝胶可以在凝胶化后进行修饰，以使用硫醇烯化学显示用于 2D 细胞培养的细胞粘附肽。此外，点击藻酸盐水凝胶的炎症程度最低，可以在几个月内保持结构完整性，并且在小鼠皮下注射时可以抑制细胞浸润。点击藻酸盐水凝胶将藻酸盐水凝胶的众多优点与强大的生物正交点击化学相结合，用于涉及细胞或生物活性分子的稳定封装或递送的组织工程应用。 (C) 2015 Elsevier Ltd. 保留所有权利。
Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedical applications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinked alginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lack of chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymer chains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulating cells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible and allows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanical properties of the click alginate hydrogel can be tuned via the total polymer concentration and the stoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can be modified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry. Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity over several months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogels combine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistry for use in tissue engineering applications involving the stable encapsulation or delivery of cells or bioactive molecules. (C) 2015 Elsevier Ltd. All rights reserved.