Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants

Abstract

Semi-crystalline thermoplastics are an important class of biomaterials with applications in creating extracorporeal and implantable medical devices. In situ release of nitric oxide (NO) from medical devices can enhance their performance via NO’s potent anti-thrombotic, bactericidal, anti-inflammatory, and angiogenic activity. However, NO-releasing semi-crystalline thermoplastic systems are limited and the relationship between polymer crystallinity and NO release profile is unknown. In this paper, the functionalization of poly(ether-block-amide) (PEBA), Nylon 12, and polyurethane tubes, as examples of semi-crystalline polymers, with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) is demonstrated via a polymer swelling method. The degree of crystallinity of the polymer plays a crucial role in both SNAP impregnation and NO release. Nylon 12, which has a relatively high degree of crystallinity, exhibits an unprecedented NO release duration of over 5 months in a low NO level, while PEBA tubing exhibits NO release over days to weeks. As a new biomedical application of NO, the NO-releasing PEBA tubing is examined as a cannula for continuous subcutaneous insulin infusion. The released NO is shown to enhance insulin absorption into the bloodstream probably by suppressing the tissue inflammatory response, and thereby benefit insulin pump therapy for diabetes management.

Blood‐Compatible Materials: Vascular Endothelium‐Mimetic Surfaces that Mitigate Multiple Cell‐Material Interactions

“…[ 48 ] Other work has also shown that NO‐releasing materials have broad‐spectrum antimicrobial activity. [ 15,28,40,58–64 ] The minimal observed antimicrobial properties of our NO‐releasing surfaces may be due to the amount of NO released. Previously published literature from our group has shown that 2.73 n m NO is required to produce a 90% reduction in bacterial biofilm viability.…”

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

“…NO releasing materials may be ideal candidates for the development of novel biomedical devices which can effectively prevent bacterial infection and thrombus formation, since NO is identified to be capable of preventing platelet activation and adhesion, and inhibiting bacterial proliferation and biofilm formation [109]. S -Nitroso- N -acetylpenicillamine (SNAP), a commonly used nitrosothiol typed NO donor, has been extensively investigated to incorporate into biomedical grade polymers to create NO releasing materials [159,160,161,162,163] because of its low cost, safety, stability during release and storage, demonstrating the potential for long-term applications [164]. Meyerhoff and Handa et al prepared NO releasing catheters by doping SNAP into the Elast-Eon E2As polymers [67].…”

S‐Nitrosoglutathione‐Based Nitric Oxide‐Releasing Nanofibers Exhibit Dual Antimicrobial and Antithrombotic Activity for Biomedical Applications

“…Nitric oxide has been of particular interest to researchers due to its antiplatelet, [ 13 ] anti‐biofilm, [ 14 ] wound healing, [ 15 ] and inflammatory‐regulating properties. [ 16 ] NO is generated within the vasculature to modulate vasodilation, prevent platelet adhesion to the endothelium, inhibit smooth muscle cell proliferation, and help maintain the endothelial cell barrier function. [ 17 ] NO is also produced by macrophages to reduce the viability of both Gram‐positive and Gram‐negative pathogens.…”