Reduction of Thrombosis and Bacterial Infection via Controlled Nitric Oxide (NO) Release fromS-Nitroso-N-acetylpenicillamine (SNAP) Impregnated CarboSil Intravascular Catheters.
Nitric oxide (NO) has many important physiological functions, including its ability to inhibit platelet activation and serve as potent antimicrobial agent. The multiple roles of NO in vivo have led to great interest in the development of biomaterials that can deliver NO for specific biomedical applications. Herein, we report a simple solvent impregnation technique to incorporate a nontoxic NO donor,S-nitroso-N-acetylpenicillamine (SNAP), into a more biocompatible biomedical grade polymer, CarboSil 20 80A. The resulting polymer-crystal composite material yields a very stable, long-term NO release biomaterial. The SNAP impregnation process is carefully characterized and optimized, and it is shown that SNAP crystal formation occurs in the bulk of the polymer after solvent evaporation. LC-MS results demonstrate that more than 70% of NO release from this new composite material originates from the SNAP embedded CarboSil phase, and not from the SNAP species leaching out into the soaking solution. Catheters prepared with CarboSil and then impregnated with 15 wt % SNAP provide a controlled NO release over a 14 d period at physiologically relevant fluxes and are shown to significantly reduce long-term (14 day) bacterial biofilm formation againstStaphylococcus epidermidisandPseudonomas aeruginosain a CDC bioreactor model. After 7 h of catheter implantation in the jugular veins of rabbit, the SNAP CarboSil catheters exhibit a 96% reduction in thrombus area (0.03 ± 0.01 cm2/catheter) compared to the controls (0.84 ± 0.19 cm2/catheter) (n= 3). These results suggest that SNAP impregnated CarboSil can become an attractive new biomaterial for use in preparing intravascular catheters and other implanted medical devices.
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Yaqi
Y
Wo
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Elizabeth J
EJ
Brisbois
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Jianfeng
J
Wu
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Zi
Z
Li
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Terry C
TC
Major
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Azmath
A
Mohammed
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Xianglong
X
Wang
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Alessandro
A
Colletta
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Joseph L
JL
Bull
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Adam J
AJ
Matzger
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Chuanwu
C
Xi
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Robert H
RH
Bartlett
Department of Chemistry, Department of Surgery, University of Michigan Medical Center, Department of Environmental Health Sciences, and Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
Mark E
ME
Meyerhoff
S-nitroso-N-acetylpenicillamine (SNAP); antimicrobial catheters; bactericidal; nitric oxide; solvent impregnation; thromboresistance