Department of Biomedical Engineering, Northwestern University, Evanston, Illinois.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Biotechnol Bioeng. 2018 Sep;115(9):2356-2364. doi: 10.1002/bit.26741. Epub 2018 Jun 25.
Islet transplantation is a promising therapeutic option for type 1 diabetes mellitus, yet the current delivery into the hepatic portal vasculature is limited by poor engraftment. Biomaterials have been used as a means to promote engraftment and function at extrahepatic sites, with strategies being categorized as encapsulation or microporous scaffolds that can either isolate or integrate islets with the host tissue, respectively. Although these approaches are typically studied separately using distinct material platforms, herein, we developed nondegradable polyethylene glycol (PEG)-based hydrogels for islet encapsulation or as microporous scaffolds for islet seeding to compare the initial engraftment and function of islets in syngeneic diabetic mice. Normoglycemia was restored with transplantation of islets within either encapsulating or microporous hydrogels containing 700 islet equivalents (IEQ), with transplantation on microporous hydrogels producing lower blood glucose levels at earlier times. A glucose challenge test at 1 month after transplant indicated that encapsulated islets had a delay in glucose-stimulated insulin secretion, whereas microporous hydrogels restored normoglycemia in times consistent with native pancreata. Encapsulated islets remained isolated from the host tissue, whereas the microporous scaffolds allowed for revascularization of the islets after transplant. Finally, we compared the inflammatory response after transplantation for the two systems and noted that microporous hydrogels had a substantially increased presence of neutrophils. Collectively, these findings suggest that both encapsulation and microporous PEG scaffold designs allow for stable engraftment of syngeneic islets and the ability to restore normoglycemia, yet the architecture influences islet function and responsiveness after transplantation.
胰岛移植是治疗 1 型糖尿病的一种很有前途的治疗方法，但目前将其移植到肝门静脉系统受到植入效果不佳的限制。生物材料已被用作促进肝外部位植入和功能的手段，其策略可分为分别隔离或整合胰岛与宿主组织的包封或微孔支架。尽管这些方法通常使用不同的材料平台分别进行研究，但在这里，我们开发了不可降解的聚乙二醇（PEG）基水凝胶用于胰岛包封或作为胰岛接种的微孔支架，以比较同基因糖尿病小鼠中胰岛的初始植入和功能。用包含 700 个胰岛当量（IEQ）的包封或微孔水凝胶中的胰岛移植可恢复正常血糖水平，而在微孔水凝胶中移植可更早地降低血糖水平。移植后 1 个月的葡萄糖刺激胰岛素分泌试验表明，包封的胰岛延迟了葡萄糖刺激的胰岛素分泌，而微孔水凝胶则使正常血糖恢复时间与天然胰腺一致。包封的胰岛仍然与宿主组织隔离，而微孔支架允许胰岛在移植后再血管化。最后，我们比较了两种系统移植后的炎症反应，发现微孔水凝胶中中性粒细胞的存在明显增加。总之，这些发现表明，包封和微孔 PEG 支架设计都允许同基因胰岛的稳定植入，并能够恢复正常血糖水平，但结构会影响移植后的胰岛功能和反应性。
