A Zwitterionic Polyurethane Nanoporous Device with Low Foreign‐Body Response for Islet Encapsulation. Issue 39 (6th August 2021) - Liu, Qingsheng
Abstract: Encapsulation of insulin‐producing cells is a promising strategy for treatment of type 1 diabetes. However, engineering an encapsulation device that is both safe (i.e., no cell escape and no breakage) and functional (i.e., low foreign‐body response (FBR) and high mass transfer) remains a challenge. Here, a family of zwitterionic polyurethanes (ZPU) with sulfobetaine groups in the polymer backbone is developed, which are fabricated into encapsulation devices with tunable nanoporous structures via electrospinning. The ZPU encapsulation device is hydrophilic and fouling‐resistant, exhibits robust mechanical properties, and prevents cell escape while still allowing efficient mass transfer. The ZPU device also induces a much lower FBR or cellular overgrowth upon intraperitoneal implantation in C57BL/6 mice for up to 6 months compared to devices made of similar polyurethane without the zwitterionic modification. The therapeutic potential of the ZPU device is shown for islet encapsulation and diabetes correction in mice for ≈3 months is demonstrated. As a proof of concept, the scalability and retrievability of the ZPU device in pigs and dogs are further demonstrated. Collectively, these attributes make ZPU devices attractive candidates for cell encapsulation therapies. Abstract : A zwitterionic nanofibrous islet encapsulation device made of sulfobetaine‐modified polyurethane is reported. The device is mechanically robust, effective in preventing cell entrance or escape, hydrophilic with facile mass transfer, and biocompatible with low levels of fibrotic deposition in mice, dogs, and pigs. These attributes make it an attractive candidate for safe delivery of insulin‐producing cells to treat type 1 diabetes.