An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport

Lab Chip. 2017 May 16;17(10):1778-1792. doi: 10.1039/c7lc00096k.

Abstract

Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications. Specifically, we demonstrate that the SNM-based intravascular BAP with ∼10 and ∼40 nm pore sized membranes support high islet viability (>60%) and functionality (<15 minute insulin response to glucose stimulation) at clinically relevant islet densities (5700 and 11 400 IE per cm2) under convection in vitro. In vivo studies with ∼10 nm pore sized SNM in a porcine model showed high islet viability (>85%) at clinically relevant islet density (5700 IE per cm2), c-peptide concentration of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection. These promising findings offer insights on the development of next generation of full-scale intravascular devices to treat T1D patients in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Survival
  • Equipment Design
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / physiology
  • Membranes, Artificial*
  • Mice
  • Nanopores*
  • Pancreas, Artificial*
  • Prosthesis Design
  • Silicon / chemistry
  • Swine

Substances

  • Membranes, Artificial
  • Silicon