An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport. Issue 10 (20th April 2017)

• Record Type: Journal Article
• Authors: Song, Shang; Blaha, Charles; Moses, Willieford; Park, Jaehyun; Wright, Nathan; Groszek, Joey; Fissell, William; Vartanian, Shant; Posselt, Andrew M.; Roy, Shuvo
• Is Part Of: Lab on a chip. Volume 17:Issue 10(2017)
• Page Start: 1778
• Page End: 1792
• Publication Date: 2017-04-20
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/c7lc00096k
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : The SNM-based iBAP demonstrates viability and functionality at clinically relevant cell density and hemocompatibility under convective transport in a porcine model. 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 cm 2 ) 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 cm 2 ), 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.