In Situ Nitric Oxide Generating Nano-Bioactive Glass-Based Coatings and Its Therapeutic Ion Release toward Attenuating Implant-Associated Fibrosis and Infection

Nitric oxide (NO) is a potent gasotransmitter that exhibits a pleiotropic effect in regulating homeostasis and pathophysiology. Though it is a versatile biomaterial, silicone-based devices are still challenged by implant-associated infections and fibrous capsule formation complications. Here, a NO-generating (NOgen) interface is developed from copper or strontium-doped mesoporous bioactive glass-based coating on silicone substrates to facilitate metal-ion catalysis of endogenous S-nitrosothiols. The copper or strontium-based interfaces can generate physiologically relevant NO levels, which have bactericidal and antithrombotic effects to combat implant-associated early onsite infection and thrombosis. The NO generated in tandem with the low therapeutic release of strontium ions from the NOgen interface regulates cellular fate pertaining to fibroblasts, macrophages, and endothelial cells. Strontium suppresses the collagen expression and migration of activated fibroblasts while favoring M2 phenotype bias in macrophages. Differential NO flux observed over time from NOgen interfaces helps switch macrophages from proinflammatory M1 phenotype to M2 anti-inflammatory phenotype. Moreover, the synergistic effect of leachate and NO generated by the silicone substrate demonstrates a proangiogenic effect by aiding endothelial network maturation in vitro. Thus, the multifunctional features of the developed strontium-doped bioactive glass-based coating hold promise in regulating local immune-micromilieu and attenuating implant-associated fibrosis of silicone-based implantable devices.