Prevascularized retrievable hybrid implant to enhance function of subcutaneous encapsulated islets.

Replacement of pancreatic β-cells is one of the most promising treatment options for treatment of type 1 diabetes (T1D), however toxic immunosuppressive drugs are required. In this study, we aim to deliver allogeneic β-cell therapies without anti-rejection drugs using a bioengineered hybrid device that contains microencapsulated β-cells inside 3D polycaprolactone (PCL) scaffolds printed using melt electrospin writing (MEW). Mouse β-cell (MIN6) pseudo-islets and QS-mouse islets are encapsulated in alginate microcapsules, without affecting viability and insulin secretion. Microencapsulated MIN6 cells are then seeded within 3D MEW scaffolds, and these hybrid devices implanted subcutaneously in streptozotocin-treated diabetic NOD/SCID and BALB/c mice. Similar to NOD/SCID mice, blood glucose levels (BGL) are lowered from 30.1 to 4.8 mmol/L in 25-41 days in BALB/c. In contrast, microencapsulated islets placed in pre-vascularized MEW scaffold 3 weeks after implantation in BALB/c mice normalize BGL (〈12 mmol/L) more rapidly, lasting for 60 - 105 days. The lowering of glucose levels is confirmed by an intraperitoneal glucose tolerance test. Vascularity within the implanted grafts is demonstrated and quantified by 3D-doppler ultrasound, with a linear increase over 4 weeks (r = 0.65). Examination of the device at 5 weeks shows inflammatory infiltrates of neutrophils, macrophages and B-lymphocytes on the MEW scaffolds but not on microcapsules, which have infrequent pro-fibrotic walling. In conclusion, we demonstrate the fabrication of an implantable and retrievable hybrid device for vascularization and enhancing the survival of encapsulated islets implanted subcutaneously in an allotransplantation setting without immunosuppression. This study provides proof-of-concept for the application of such devices for human use, however, will require modifications to allow translation to people with T1D.