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

作者:Song Shang; Blaha Charles; Moses Willieford; Park Jaehyun; Wright Nathan; Groszek Joey; Fissell William; Vartanian Shant; Posselt Andrew M; Roy Shuvo*
来源:Lab on a Chip, 2017, 17(10): 1778-1792.
DOI:10.1039/c7lc00096k

摘要

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 similar to 10 and similar to 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 11400 IE per cm(2)) under convection in vitro. In vivo studies with similar to 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 fullscale intravascular devices to treat T1D patients in the future.

  • 出版日期2017-5-21