It has been previously demonstrated that metal nanoparticles embedded into polymeric materials doped with nitric oxide (NO) donor compounds can accelerate the release rate of NO for therapeutic applications. Despite the advantages of elevated NO surface flux for eradicating opportunistic bacteria in the initial hours of application, metal nanoparticles can often trigger a secondary biocidal effect through leaching that can lead to unfavorable cytotoxic responses from host cells. Alternatively, copper-based metal organic frameworks (MOFs) have been shown to stabilize Cu 2+/1+ via coordination while demonstrating longerterm catalytic performance compared to their salt counterparts. Herein, the practical application of MOFs in NO-releasing polymeric substrates with an embedded NO donor compound was investigated for the first time. By developing composite thermoplastic silicon polycarbonate polyurethane (TSPCU) scaffolds, the catalytic effects achievable via intrapolymeric interactions between an MOF and NO donor compound were investigated using the water-stable copper-based MOF H 3 [(Cu 4 Cl) 3 (BTTri) 8 -(H 2 O) 12 ]•72H 2 O (CuBTTri) and the NO donor Snitroso-N-acetyl-penicillamine (SNAP). By creating a multifunctional triple-layered composite scaffold with CuBTTri and SNAP, the surface flux of NO from catalyzed SNAP decomposition was found tunable based on the variable weight percent CuBTTri incorporation. The tunable NO surface fluxes were found to elicit different cytotoxic responses in human cell lines, enabling application-specific tailoring. Challenging the TSPCU−NO−MOF composites against 24 h bacterial growth models, the enhanced NO release was found to elicit over 99% reduction in adhered and over 95% reduction in planktonic methicillin-resistant Staphylococcus aureus, with similar results observed for Escherichia coli. These results indicate that the combination of embedded MOFs and NO donors can be used as a highly efficacious tool for the early prevention of biofilm formation on medical devices.
When flowing whole blood contacts medical device surfaces, the most common blood–material interactions result in coagulation, inflammation, and infection. Many new blood‐contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood‐contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet‐, leukocyte‐, and bacteria‐surface interactions. This work demonstrates that new blood‐compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood‐contacting medical devices.
The metal–organic framework (MOF) CuBTTri, H3[(Cu4Cl)3(BTTri)8] (where H3BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene), is a promising catalyst for the development of antithrombotic medical device materials via localized nitric oxide (NO) generation from endogenous S-nitrosothiols. This work evaluates the effects of three key parameters of CuBTTri-embedded polyurethane composite materials—MOF preparation/particle size, MOF loading, and polymer concentration—on the rate of NO generation. We discovered that CuBTTri preparation and particle size have a significant impact on NO generation. Specifically, hand-ground MOF particles (0.3 ± 0.1 µm diameter) generate NO at greater rates compared to larger as-prepared, raw MOF particles (0.4 ± 0.2 µm diameter) and smaller, filtered MOF particles (0.2 ± 0.1 µm diameter) for composite materials. This finding contradicts previous research for CuBTTri powder which found that the smaller the particles, the greater the catalytic rate. In examining the effects of MOF loading and polymer concentration, our data show that increasing these parameters generally results in increased rates of NO generation; though thresholds appear to exist in which increasing these parameters results in diminishing returns and impedes NO generation capacity for certain composite formulations. We found that polymer concentration is the key determinant of water absorptivity and statistically significant decreases in water uptake accompany statistically significant increases in NO generation. It was also found that formulations with relatively high MOF loadings and low polymer concentrations or low MOF loadings and high polymer concentrations inhibit the rate of NO generation. In summary, this research provides a framework for more strategic selections of key parameters when fabricating composite materials for medical device applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.