Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226000, China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226000, China.
ACS Biomater Sci Eng. 2024 Apr 8;10(4):2486-2497. doi: 10.1021/acsbiomaterials.4c00015. Epub 2024 Mar 6.
Islet or β-cell transplantation is currently considered to be the ideal treatment for diabetes, and three-dimensional (3D) bioprinting of a bionic pancreas with physiological stiffness is considered to be promising for the encapsulation and transplantation of β-cells. In this study, a 5%GelMA/2%AlgMA hybrid hydrogel with pancreatic physiological stiffness was constructed and used for β-cell encapsulation, 3D bioprinting, and in vivo transplantation to evaluate glycemic control in diabetic mice. The hybrid hydrogel had good cytocompatibility and could induce insulin-producing cells (IPCs) to form pseudoislet structures and improve insulin secretion. Furthermore, we validated the importance of betacellulin (BTC) in IPCs differentiation and confirmed that IPCs self-regulation was achieved by altering the nuclear and cytoplasmic distributions of BTC expression. In vivo transplantation of diabetic mice quickly restored blood glucose levels. In the future, 3D bioprinting of β-cells using biomimetic hydrogels will provide a promising platform for clinical islet transplantation for the treatment of diabetes.
胰岛或β细胞移植目前被认为是治疗糖尿病的理想方法，而具有生理硬度的仿生胰腺的三维（3D）生物打印被认为有望用于β细胞的包封和移植。在这项研究中，构建了一种具有胰腺生理硬度的 5%GelMA/2%AlgMA 混合水凝胶，用于β细胞包封、3D 生物打印和体内移植，以评估糖尿病小鼠的血糖控制。该混合水凝胶具有良好的细胞相容性，并能诱导胰岛素产生细胞（IPCs）形成假胰岛结构，提高胰岛素分泌。此外，我们验证了 BTC（β细胞素）在 IPCs 分化中的重要性，并证实通过改变 BTC 表达的核质分布实现了 IPCs 的自我调节。糖尿病小鼠的体内移植能迅速恢复血糖水平。将来，使用仿生水凝胶的 3D 生物打印β细胞将为临床胰岛移植治疗糖尿病提供一个有前景的平台。
