Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 48, Pages 56931-56943Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c17248
Keywords
metal organic framework; nitric oxide; infection; catalysis; S-nitrosothiols
Funding
- National Institutes of Health [R01HL140301, R01HL134899]
- NIH [P41GM111135]
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The combination of metal organic frameworks (MOFs) and NO donors can effectively accelerate the release rate of NO for therapeutic applications, preventing biofilm formation on medical devices. Through intrapolymeric interactions, tunable NO surface fluxes can elicit different cytotoxic responses in human cell lines, showing potential for application-specific tailoring. Enhanced NO release from the composite materials was found to significantly reduce bacterial growth, indicating a promising approach for combating opportunistic bacteria.
It has been previously demonstrated that metal nano-particles 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 longer-term 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[(Cu4Cl)(3) (BTTri)(8)-(H2O)(12)]center dot 72H(2)O (CuBTTri) and the NO donor S-nitroso-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.
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