School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
Biomaterials. 2015 May;50:30-7. doi: 10.1016/j.biomaterials.2015.01.048. Epub 2015 Feb 14.
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.
海藻酸盐水凝胶是具有良好特性的、生物惰性的材料，被广泛应用于药物、蛋白质和细胞的输送等多种生物医学领域。然而，传统的化学交联海藻酸盐水凝胶的形成通常采用化学策略，由于缺乏化学选择性，这些策略可能对生物有害。在这项工作中，我们在海藻酸盐聚合物链上引入了四嗪和降冰片烯基团，随后形成了共价交联的点击海藻酸盐水凝胶，能够在不损伤细胞的情况下对其进行封装。快速、生物正交和特异性的点击反应是不可逆的，并且可以轻松地将高封装后活力的细胞纳入其中。点击海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。点击海藻酸盐水凝胶可以在凝胶化后进行修饰，使用硫醇-烯点击化学在二维细胞培养中显示细胞黏附肽。此外，点击海藻酸盐水凝胶的炎症反应很小，可以在几个月内保持结构完整性，并且在小鼠皮下注射时排斥细胞浸润。点击海藻酸盐水凝胶将海藻酸盐水凝胶的众多优点与强大的生物正交点击化学结合在一起，可用于涉及细胞或生物活性分子稳定封装或输送的组织工程应用。
