Robert van Lith, M.S. 

Ph.D. Student, Biomedical Engineering
B.S./M.S. Biomedical Engineering, Eindhoven University of Technology , The Netherlands

Contact: r-lith at northwestern.edu

Research Interests: Nitric oxide delivery, microparticles, biomaterials, vascular tissue engineering

Synthetic vascular grafts such as ePTFE and Dacron are used commonly for replacing dysfunctional blood vessels, e.g. due to diseases such as atherosclerosis. However, in vessels with diameters smaller than 6 mm, for example coronary arteries, synthetic grafts suffer from low patency rates due to the high inherent thrombogenicity of the materials and neo-intimal hyperplasia, leading to occlusion of the grafts.

Nitric oxide is a small molecule that is secreted at fairly steady levels by endothelial cells, the natural lining of blood vessels. It is known to prevent adhesion and activation of platelets (which is involved in thrombosis), stimulate endothelial proliferation and inhibit overproliferation of smooth muscle cells (two major causes of neo-intimal hyperplasia and subsequent occlusion). Therefore we are aiming at developing strategies for local delivery of nitric oxide to ultimately improve the survival rates of synthetic grafts in small-diameter blood vessels.

Currently, we are looking into encapsulating a diazeniumdiolated drug in polymer PLLA particles. Diazeniumdiolated compounds can spontaneously release NO when placed in a physiological solution (e.g. blood), but do so in a rapid fashion. By encapsulating the drug, we intend to achieve prolonged delivery of NO. Also, the drug we are currently investigating can stimulate cells to secrete more NO themselves, likely by virtue of the drug's numerous arginine moieties, the precursor for nitric oxide synthesis. Hence, we have a unique combinatory system of exogenous NO delivery and induction of endogenous NO production.

Ultimately, we hope to incorporate this particulate system in synthetic grafts to achieve significant in vivo levels of NO for at least several weeks, enough to overcome the initial inflammatory response that is causes the main neo-intimal hyperplasia and thrombosis problems. An alternative use of this particulate system may be to treat vessels perivascularly after angioplasty procedures to minimize restenosis.