Biomaterial and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Assam, India.
Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata, West Bengal, India.
Biomaterials. 2018 Dec;187:1-17. doi: 10.1016/j.biomaterials.2018.09.037. Epub 2018 Sep 25.
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.
胰岛移植被认为是治疗 1 型糖尿病最有前途的方法。然而，其临床成功率受到长期培养中胰岛功能障碍的限制。在这项研究中，我们利用桑蚕丝（Bombyx mori）与非桑蚕丝（Antheraea assama）混合后提供的快速自凝胶化和可注射性，得到了一种仿生水凝胶。与以前报道的丝胶凝技术不同，两种丝品种氨基酸序列的差异导致凝胶加速，而不需要任何外部刺激。凝胶研究和流变学评估表明，凝胶化时间可作为蛋白质浓度和混合比例的函数进行调节。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。此外，具有固有 Arg-Gly-Asp（RGD）的 A. assama 丝素对胰岛活力、胰岛素分泌和内皮细胞维持有显著影响。此外，这些水凝胶的应用证明了白细胞介素 4（IL-4）和地塞米松的持续释放，同时有效促进了 M2 巨噬细胞极化，维持胰岛生理学。免疫知情水凝胶在体内显示出局部调节炎症反应的能力。总之，这些结果展示了可注射丝水凝胶的有前途的特性，以及非桑蚕丝素纤维作为胰岛包封的替代生物材料的应用。
