通过乳液交联法对胰岛进行包被的性能在糖尿病啮齿动物和非人类灵长类动物中的表现。

Performance of islets of Langerhans conformally coated via an emulsion cross-linking method in diabetic rodents and nonhuman primates.

机构信息

Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Department of Biomedical Engineering, University of Miami, Miami, FL 33146, USA.

出版信息

Sci Adv. 2022 Jul;8(26):eabm3145. doi: 10.1126/sciadv.abm3145. Epub 2022 Jun 29.

Polyethylene glycol (PEG)-based conformal coating (CC) encapsulation of transplanted islets is a promising β cell replacement therapy for the treatment of type 1 diabetes without chronic immunosuppression because it minimizes capsule thickness, graft volume, and insulin secretion delay. However, we show here that our original CC method, the direct method, requiring exposure of islets to low pH levels and inclusion of viscosity enhancers during coating, severely affected the viability, scalability, and biocompatibility of CC islets in nonhuman primate preclinical models of type 1 diabetes. We therefore developed and validated in vitro and in vivo, in several small- and large-animal models of type 1 diabetes, an augmented CC method-emulsion method-that achieves hydrogel CCs around islets at physiological pH for improved cytocompatibility, with PEG hydrogels for increased biocompatibility and with fivefold increase in encapsulation throughput for enhanced scalability.

聚乙二醇（PEG）基包封涂层（CC）对移植胰岛进行包被是一种很有前途的β细胞替代治疗方法，可用于治疗 1 型糖尿病，而无需进行慢性免疫抑制，因为它可以使胶囊厚度、移植物体积和胰岛素分泌延迟最小化。然而，我们在这里展示的是，我们最初的 CC 方法，即直接方法，需要在包被过程中使胰岛暴露于低 pH 值水平并包含粘度增强剂，这严重影响了 CC 胰岛在 1 型糖尿病非人灵长类动物临床前模型中的活力、可扩展性和生物相容性。因此，我们开发并在体外和体内验证了几种 1 型糖尿病的小型和大型动物模型中的增强型 CC 方法——乳剂方法，该方法可以在生理 pH 值下在胰岛周围形成水凝胶 CC，以提高细胞相容性，使用 PEG 水凝胶提高生物相容性，并使封装通量增加五倍，从而提高可扩展性。