Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation

Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation
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DOI:
10.1038/s41467-019-13238-7
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发表时间:
2019-11-20
影响因子:
16.6
通讯作者:
Ma, Minglin
Ma, Minglin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu, Qingsheng;Chiu, Alan;Ma, Minglin

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植入生物材料和医疗器械的异物反应(FBR)很常见,可能损害植入物的功能或导致并发症。例如,在细胞包裹中,细胞结构周围的细胞过度生长(CO)和纤维化可以减少氧气、营养物质和代谢废物的质量转移,破坏细胞功能并导致移植失败。因此,减缓FBR或CO的材料将在生物医学中具有广泛的应用。在这里,我们报告了一组两性离子,磺基甜菜碱(SB)和羧基甜菜碱(CB)的海藻酸盐的修改,可重复地减轻在小鼠,狗和猪的植入海藻酸盐微胶囊的CO。使用修饰的藻酸盐(SB-藻酸盐),我们还证明了在化学诱导的糖尿病小鼠模型中胰岛包封的改善结果。这些两性离子修饰的藻酸盐可能有助于开发1型糖尿病和其他糖尿病缺陷疾病的细胞包封疗法。
Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.