An injection of hydrogel-encapsulated islets that controls blood glucose levels over long term would provide a much needed alternative treatment for type 1 diabetes mellitus (T1DM). To this end, we tested the feasibility of using an injectable polyethylene glycol (PEG) hydrogel as a scaffold for islet encapsulation. Encapsulated islets cultured in vitro for 6 days showed excellent cell viability and released insulin with higher basal and stimulated insulin secretion than control islets. Host responses to PEG hydrogels were studied by injecting PEG hydrogels (no treatment and vehicle controls used) into the peritoneal cavities of B6D2F1 mice and monitoring alterations in body weight, food and water intake, and blood glucose levels. After 2 weeks, peritoneal cavity cells were harvested, followed by hydrogel retrieval, and extraction of spleens. Body weights, food and water intake, and blood glucose levels were unaltered in mice injected with hydrogels compared to no treatment and vehicle-injected control mice. Frozen sections of a hydrogel showed the presence of tissues and small number of immune cells surrounding the hydrogel but no cell infiltration into the hydrogel bulk. Spleen sizes were not significantly different under the experimental conditions. Peritoneal cavity cells were slightly higher in mice injected with hydrogels compared to control mice but no statistical difference between vehicle- and hydrogel-injected mice was noted. As an in vivo feasibility study, streptozotocin-induced diabetic mice were injected with vehicle or hydrogels containing 50 islets each into two sites, the peritoneal cavity and a subcutaneous site on the back. Transient control of blood glucose levels were observed in mice injected with hydrogels containing islets. In summary, we developed an injectable PEG hydrogel that supported islet function and survival in vitro and in vivo and elicited only a mild host response. Our work illustrates the feasibility of using injectable PEG hydrogels for islet encapsulation.

中文翻译：

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用于胰岛封装的可注射聚乙二醇水凝胶：体外和体内表征

注射长期控制血糖水平的水凝胶包裹的胰岛将为 1 型糖尿病 (T1DM) 提供一种急需的替代治疗方法。为此，我们测试了使用可注射聚乙二醇 (PEG) 水凝胶作为胰岛封装支架的可行性。体外培养 6 天的封装胰岛显示出极好的细胞活力，并且释放的胰岛素比对照胰岛具有更高的基础和刺激胰岛素分泌。通过将 PEG 水凝胶（未使用治疗和载体对照）注射到 B6D2F1 小鼠的腹腔中并监测体重、食物和水摄入量以及血糖水平的变化来研究宿主对 PEG 水凝胶的反应。2 周后，收获腹腔细胞，随后进行水凝胶回收和脾脏提取。与未治疗和注射载体的对照小鼠相比，注射水凝胶的小鼠的体重、食物和水的摄入量以及血糖水平没有改变。水凝胶的冷冻切片显示水凝胶周围存在组织和少量免疫细胞，但没有细胞浸润到水凝胶主体中。脾脏大小在实验条件下没有显着差异。与对照小鼠相比，注射水凝胶的小鼠的腹腔细胞略高，但没有注意到注射载体和水凝胶的小鼠之间的统计学差异。作为体内可行性研究，链脲佐菌素诱导的糖尿病小鼠被注射到两个部位，腹腔和背部皮下部位，每个含有 50 个胰岛的载体或水凝胶。在注射含有胰岛的水凝胶的小鼠中观察到血糖水平的瞬时控制。总之，我们开发了一种可注射的 PEG 水凝胶，在体外和体内支持胰岛功能和存活，并且仅引起温和的宿主反应。我们的工作说明了使用可注射 PEG 水凝胶进行胰岛封装的可行性。