Riley Robb Hall 322, Ithaca, NY, 14853, USA.
Adv Healthc Mater. 2019 Jun;8(12):e1900423. doi: 10.1002/adhm.201900423. Epub 2019 May 21.
Islet encapsulation and transplantation promises to improve upon current treatments for type 1 diabetes mellitus, though several limitations remain. Macroscale devices have been designed for in vivo transplantation and retrieval, but traditional geometries do not support clinically adequate mass transfer of nutrients to and insulin from the encapsulated tissue. Microcapsule technologies have improved mass transfer properties, but their clinical translation remains challenging as their complete retrieval is difficult, should the graft become a safety concern. Here, the design, characterization and testing of a novel encapsulation structure, comprised of elastomer-reinforced interconnected toroidal hydrogels is reported. These donut-shaped hydrogels feature a high surface area, higher than conventional spherical capsules of the same volume, bestowing suitable mass transport conditions, while allowing interconnection and reversible deformation for intraperitoneal implantation and retrieval. Diabetes correction up to 12 weeks and complete retrieval is achieved in a diabetic mouse model, providing a proof-of-concept for the potential application as a type 1 diabetes cell replacement therapy.
胰岛封装和移植有望改善目前 1 型糖尿病的治疗方法，但仍存在一些局限性。已经设计了用于体内移植和检索的大规模设备，但传统的几何形状不能支持临床所需的营养物质向封装组织的充分质量传递和胰岛素从封装组织的输出。微胶囊技术改善了质量传递特性，但由于其完全检索困难，如果移植物成为安全问题，其临床转化仍然具有挑战性。在这里，报告了一种由弹性体增强的互连的环形水凝胶组成的新型封装结构的设计、表征和测试。这些甜甜圈形状的水凝胶具有高表面积，高于相同体积的传统球形胶囊，赋予合适的质量传递条件，同时允许互连和可恢复变形，以便进行腹腔内植入和检索。在糖尿病小鼠模型中实现了长达 12 周的糖尿病纠正和完全检索，为作为 1 型糖尿病细胞替代疗法的潜在应用提供了概念验证。
