Covalent stabilization of alginate hydrogel beads via Staudinger ligation: assessment of poly(ethylene glycol) and alginate cross-linkers.
Covalent stabilization of alginate hydrogel beads via Staudinger ligation: assessment of poly(ethylene glycol) and alginate cross-linkers.
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DOI：
10.1002/jbm.a.33162
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发表时间：
2011-10
影响因子：
4.9
通讯作者：
Stabler, Cherie L.
中科院分区：
文献类型：
--
作者：
Gattas-Asfura, Kerim M.;Fraker, Christopher A.;Stabler, Cherie L.
藻酸盐水凝胶胶囊内的细胞封装在组织工程中具有广泛的应用。为了改善离子交联藻酸盐水凝胶的固有不稳定性，我们之前证明了使用 1-甲基-2-二苯基膦对苯二甲酸酯 (MDT) 封端的聚乙二醇连接体通过化学选择性施陶丁格连接对 Ba2+ 交联藻酸盐叠氮珠进行共价稳定。在本研究中，我们使用 MDT 基团对变体 PEG、线性和支化以及藻酸盐聚合物进行功能化，以评估尺寸、结构设计、官能团数量和电荷对所得水凝胶珠的影响。所有交联剂都增强了海藻酸盐珠的共价稳定性，通过 Ba2+ 螯合显着降低了膨胀和溶解阻力。 MDT 功能化海藻酸盐产生最稳定和均匀的珠子，即使在 EDTA 暴露后也具有最大的限制性渗透性。将 MIN6 细胞共封装在交联藻酸盐水凝胶珠中对活力的影响最小，而培养后的增殖程度随交联剂类型的不同而变化。总而言之，结果表明，控制交联剂结构设计可以使所得藻酸盐珠的特性具有灵活性。使用这些化学选择性藻酸盐和基于 PEG 的交联剂对藻酸盐水凝胶珠进行共价稳定，为细胞封装提供了独特的平台。
Cellular encapsulation within alginate hydrogel capsules has broad applications in tissue engineering. In seeking to improve the inherent instability of ionically cross-linked alginate hydrogels, we previously demonstrated the covalent stabilization of Ba2+ cross-linked alginate-azide beads via chemoselective Staudinger ligation using a 1-methyl-2-diphenylphosphino-terephthalate (MDT) terminated poly(ethylene glycol) linker. In this study, we functionalized variant PEG, linear and branched, and alginate polymers with MDT groups to evaluate the effect of size, structural design, number of functional groups, and charge on the resulting hydrogel bead. All cross-linkers resulted in enhanced covalent stabilization of alginate beads, with significant decreases in swelling and resistance to dissolution via Ba2+ chelation. The MDT-functionalized alginate resulted in the most stable and homogeneous bead, with the most restrictive permeability even after EDTA exposure. Co-encapsulation of MIN6 cells within the cross-linked alginate hydrogel beads resulted in minimal effects on viability, whereas the degree of proliferation following culture varied with cross-linker type. Altogether, the results illustrate that manipulating the cross-linker structural design permits flexibility in resulting alginate beads characteristics. Covalent stabilization of alginate hydrogel beads with these chemoselective alginate and PEG-based cross-linkers provides a unique platform for cellular encapsulation.
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