Self-Cleaning Membrane to Extend the Lifetime of an Implanted Glucose Biosensor

Abstract

The lifetime and efficacy of a subcutaneously implanted glucose biosensor could be greatly improved by a self-cleaning membrane capable of periodic physical removal of adhered cells associated with the foreign body reaction. Previously, we reported thermoresponsive double network nanocomposite (DNNC) membrane comprised of poly(N-isopropylacrylamide) (PNIPAAm) and embedded polysiloxane nanoparticles. When the membrane was thermally cycled above and below its volume phase transition temperature (VPTT, ~33–35 °C), the associated deswelling and reswelling, respectively, led to in vitro cell release. Herein, this membrane design was tailored to meet the specific demands of a subcutaneously implanted glucose biosensor and critical functional properties were assessed. First, N-vinylpyrrolidone (NVP) comonomer increased the VPTT to ~38 °C so that the membrane would be swollen and thus more permeable to glucose in the “off-state” (i.e. no heating) while residing in the subcutaneous tissue (~35 °C). Second, glucose diffusion kinetics though the DNNC membrane was experimentally measured in its deswollen and reswollen states. A cylindrical DNNC membrane with dimensions considered suitable for implantation (1.5×5 mm, diameter × length) was used to model the glucose diffusion lag time. In addition, the DNNC cylinder was used to observe dimensional changes associated with deswelling and reswelling. Non-cytotoxicity was confirmed and self-cleaning was assessed in vitro in terms of thermally-driven cell release to confirm the potential of the DNNC membrane to control biofouling.

A Layer-by-Layer Approach To Retain a Fluorescent Glucose Sensing Assay within the Cavity of a Hydrogel Membrane

“…45,66,67 Under the assumption that each chamber maintained a uniform concentration, eq 2 was simplified to eq 3: 45 where Q t is the amount of glucose transferred through the membrane at a specific time t , A is the area of the hydrogel exposed to either the donor or receiver chamber, C i is the initial stock glucose concentration within the donor channel at t = 0, and T is the thickness of the hydrogel membrane.…”

Self‐Cleaning, Thermoresponsive P(NIPAAm‐co‐AMPS) Double Network Membranes for Implanted Glucose Biosensors

“…In order to minimize biofouling, membranes relying on a passive (i.e., anti‐fouling) strategy have been most widely studied, including those based on poly(ethylene glycol) diacrylate (PEG‐DA) hydrogels, poly(tetrafluoroethylene) (PTFE), e‐PTFE, poly(vinyl alcohol) (PVA) hydrogels, polyhydroxyethyl‐methacrylate (PHEMA) hydrogels, and poly‐L‐lactic acid (PLLA) . In contrast, we have reported “self‐cleaning membranes” based on poly( N ‐isopropylacrylamide) (PNIPAAm) hydrogels which utilize an active (i.e., foul‐releasing) mechanism to physically remove attached cells . PNIPAAm hydrogels are thermoresponsive, deswelling and reswelling when heated above and cooled below their volume phase transition temperature (VPTT, ≈33–35 °C), respectively .…”

A Novel Triple-Responsive Hydrogels Based on 2-(Dimethylamino) Ethyl Methacrylate by Copolymerization With 2-(N-morpholino) Ethyl Methacrylate

“…Due to the unique characteristics such as high swelling ratio, softness and elasticity, hydrogels find various application fields. pH-and temperature-sensitive hydrogels are promising materials for controlled drugdelivery systems (8,9), agriculture (10,11), biosensors (12,13), tissue engineering (14,15) and water purification, and have many other medical and industrial applications (16)(17)(18). For this purpose, the synthesis of hydrogels possessing wide variety of functional groups like hydroxyl groups, amino groups or carboxyl groups have been more and more studied by researchers.…”