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Immunomodulatory injectable silk hydrogels maintaining functional islets and promoting anti-inflammatory M2 macrophage polarization
Biomaterials ( IF 14.0 ) Pub Date : 2018-09-25 , DOI: 10.1016/j.biomaterials.2018.09.037
Manishekhar Kumar , Prerak Gupta , Sohenii Bhattacharjee , Samit K. Nandi , Biman B. Mandal

Islet transplantation is considered the most promising treatment for type 1 diabetes. However, the clinical success is limited by islet dysfunction in long-term culture. In this study, we have utilized the rapid self-gelation and injectability offered by blending of mulberry silk (Bombyx mori) with non-mulberry (Antheraea assama) silk, resulting in a biomimetic hydrogel. Unlike the previously reported silk gelation techniques, the differences in amino acid sequences of the two silk varieties result in accelerated gelation without requiring any external stimulus. Gelation study and rheological assessment depicts tuneable gelation as a function of protein concentration and blending ratio with minimum gelation time. In vitro biological results reveal that the blended hydrogels provide an ideal 3D matrix for primary rat islets. Also, A. assama fibroin with inherent Arg-Gly-Asp (RGD) shows significant influence on islet viability, insulin secretion and endothelial cell maintenance. Furthermore, utility of these hydrogels demonstrate sustained release of Interleukin-4 (IL-4) and Dexamethasone with effective M2 macrophage polarization while preserving islet physiology. The immuno-informed hydrogel demonstrates local modulation of inflammatory responses in vivo. Altogether, the results exhibit promising attributes of injectable silk hydrogel and the utility of non-mulberry silk fibroin as an alternative biomaterial for islet encapsulation.



中文翻译:

维持功能性胰岛和促进抗炎M2巨噬细胞极化的免疫调节注射丝绸水凝胶

胰岛移植被认为是1型糖尿病最有前途的治疗方法。但是,长期培养中的胰岛功能障碍限制了临床成功。在这项研究中,我们利用了桑蚕丝(Bombyx mori)与非桑蚕丝(Antheraea assama)的掺混所提供的快速自胶凝性和可注射性,从而产生了仿生水凝胶。与以前报道的丝绸凝胶技术不同,两种丝绸品种的氨基酸序列差异导致加速凝胶化,而无需任何外部刺激。凝胶化研究和流变学评估显示,可调节的凝胶化是蛋白质浓度和混合比的函数,且凝胶化时间最短。体外生物学结果表明,混合水凝胶为原代大鼠胰岛提供了理想的3D基质。同样,具有固有Arg-Gly-Asp(RGD)的阿萨玛纤维蛋白显示出对胰岛活力,胰岛素分泌和内皮细胞维持的显着影响。此外,这些水凝胶的实用性证明了白细胞介素4(IL-4)和地塞米松的持续释放,并具有有效的M2巨噬细胞极化作用,同时还能保持胰岛的生理功能。免疫信息化的水凝胶显示出体内炎症反应的局部调节。总而言之,结果显示了可注射的丝绸水凝胶的有希望的属性以及非桑蚕丝素蛋白作为胰岛包封的替代生物材料的实用性。

更新日期:2018-09-25
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