Metal organic frameworks as heterogenous nitric oxide catalysts for use in the development of therapeutic polymer materials

Abstract

Implantable polymeric medical devices are subject to surface biofouling due to the deposition of microbial agents and the accumulation of proteins at the material interface. Consequently, medical devices which are intended for beneficial functions can become a potentially fatal threat. As a result biofouling resistant materials are vigorously sought through the manipulation of material surface properties and by eluting therapeutics on the material surface. Nitric oxide (NO) is a bioactive agent generated by most nucleated cells in the human body and is known to mediate antimicrobial and antithrombus effects while maintain the capacity to promote the proliferation of healthy tissues. As such, the development of NO releasing biomaterials is known to reduce incidences of surface biofouling. However, current NO releasing materials are limited to short lifetimes of used based on limited capacity of exogenous NO which can be incorporated into the material. In order to circumvent this problem the goal of this research is to develop a biomaterial which generates NO from an endogenously supplied source. Metal organic frameworks (MOFs) were selected for investigation as heterogeneous catalysts for the generation of NO from bioavailable NO donors, S-nitrosothiols (RSNOS). MOFs were evaluated as NO catalysts based on their capacity to react with various RSNO substrates and their maintained structural integrity under reaction conditions. Presented herein is the successful demonstration of a Cu-MOF for the catalytic generation of NO from bioavailable RSNOs donors. However, the limited stability of this proof of principle MOF in aqueous solution prompted the development of a MOF-NO catalyst that is suitable for physiological applications through tuning the organic ligands used in the construction of the framework. Finally a two-fold demonstration of the feasibility towards designing composite MOF based biomaterials is presented as blended materials prepared via commercial manufacturing processes and via surface growth of MOFs on flexible polymeric substrates.