Supporting islet function in a PVDF membrane based macroencapsulation delivery device by solvent non-solvent casting using PVP

Abstract

Type 1 diabetic (T1D) patients are life-long dependent on insulin therapy to keep their blood glucose levels under control. An alternative cell-based therapy for exogenous insulin injections is clinical islet transplantation (CIT). Currently the widespread application of CIT is limited, due to risks associated with the life-long use of immunosuppressive drugs to prevent rejection of donor cells. An immunoprotective macroencapsulation device can protect allogeneic islet cells against the host immune system and allow exploring extrahepatic transplantation sites. We report on the characterization and creation of porous polyvinylidene fluoride (PVDF) membrane-based devices intended for islet and beta-cell transplantation. We hypothesize that by incorporating polyvinyl-pyrrolidone (PVP) into a PVDF solution the permeability of PVDF membranes for insulin and glucose can be improved by solvent-non solvent casting to create submicrometer porous films. We show that the use of water-soluble PVP, can significantly increase glucose diffusion through these membranes while still having the ability to block immune cells from migrating through these membranes. Human donor islets loaded into devices made from these thin PVDF/PVP membranes showed a 92 ±  4% viability after 8 days similar to their free-floating counterparts. The glucose responsiveness of human donor islets encapsulated inside PVDF/PVP membrane-based devices was significantly improved compared to islets seeded in devices made from PVDF membranes without PVP, with a stimulation index of 3.2 for PVDF/PVP devices and 1.3 for PVDF-alone devices at day 8. Our data show that by addition of PVP as pore forming agent during membrane fabrication at a specific ratio the diffusion characteristics can be tuned such that human islet function in these closed macrodevices, can be kept at the same level as non-encapsulated islets, while the membrane can still serve as a protective barrier preventing the entry of primary human macrophages and damaging beta cells.