Extended Foreign Body Mitigation for Glucose Biosensors via Tertiary S-nitrosothiol-modified Mesoporous Silica Nanoparticle-doped Sensor Membranes.

The foreign body response (FBR) limits continuous glucose monitor longevity to 10 - 15 d because of chronic inflammation and collagen capsule formation surrounding the implant site. Nitric oxide (NO), a multifunctional bioactive molecule, has previously demonstrated potent FBR mitigation abilities. Here we evaluated the impact of polyurethane sensor membranes doped with a range of NO-release profiles achieved by primary and tertiary S-nitrosothiol-functionalized mesoporous silica nanoparticles (1° and 3°RSNO MSNs) using an in vitro approach. Experiments were performed using NO concentrations correlating to those known to be released at 1, 2, 4, and 6 weeks for each NO-releasing RSNO-MSN system. The NO-release kinetics and durations achieved by 1°/3°RSNO-MSN-doped sensor membranes proved effective at regulating pro- and anti-inflammatory cytokine secretion, inhibiting foreign body giant cell formation, preserving fibroblast migration, and reducing collagen production when evaluated using NO concentrations known to be present at 6 weeks. Such results suggested 1°/3°RSNO-MSN-doped sensor membranes have the potential to extend glucose sensor lifetime beyond the previously achieved 4 weeks. Indeed, both 1°/3°RSNO- and 3°RSNO-MSN-coated glucose sensors maintained stable mean absolute relative difference values over 6 weeks, with 1°/3°RSNO-MSN coated sensors trending lower, demonstrating the promise of extended NO-release for maintained sensor function over time.