Macroscopic porosity generation in outer hydrogel membranes to offset sensitivity loss in implantable glucose sensors

Abstract

The function of implantable glucose sensor is hindered by post-implantation effects such as biofouling and negative tissue responses both of which lead to permeability reducing fibrous encapsulation. Utilization of drug-eluting composite coatings based on dexamethasone-containing poly (lactic-coglycolic) acid (PLGA) microspheres and poly (vinyl alcohol) (PVA) hydrogel matrix has been shown to suppress inflammation over a period of 1-3 months. Herein, it is shown that these coatings provide another auxiliary venue to offset the negative effects of protein adsorption through generation of macroscopic porosity following microsphere degradation. Long-term studies in serum have indicated that, while biofouling clogs the microporosity of the hydrogel, it has been offset by the generated macroscopic porosity following microsphere degradation. This resulted in a two-fold recovery in sensor sensitivity as compared to controls. These findings suggest that the use of macroscopic porosity can reduce biofouling-induced sensitivity losses, an approach synergistic with drug-delivery based methodologies to mitigate negative tissue responses.

Porous, Dexamethasone-loaded polyurethane coatings extend performance window of implantable glucose sensors in vivo

“…As previously reported, Dex-loaded porous coatings had a porosity of ~ 85% and a pore size of ~76 μm [25], features which have been shown to enhance tissue vascularization and disrupt collagen capsule formation around implanted sensor leads [11, 22]. Moreover, several studies have reported on the angiogenic effects of texturing to increase vascularity around medical implants [11, 25, 33–35]. Though the exact mechanism by which topographical cues promote angiogenesis and tissue integration have yet to be elucidated, it is believed that pores within the 20–100 μm provide an optimal environment for transport of cellular by-products and migration of endothelial cells [39].…”

“…Dex is a potent glucocorticoid associated with diminished activation of immune cells and up-regulation of anti-inflammatory cytokines [21, 29, 30], yet localized delivery of Dex is often accompanied by decreased vascularity at the sensor-tissue interface [20, 21, 30–32]. It is also well established that surface texturing with feature sizes on the order of cellular dimensions can induce blood vessel formation around medical implants [11, 25, 33–35]. …”