Collaborative Research: Modeling the Growth and Adhesion of Collaborative Research: Modeling the Growth and Adhesion of Auricular Chondrocytes under Controlled Flow ConditionsAuricular Chondrocytes under Controlled Flow Conditions

Department of Mathematics, University of Houston1, The Texas Heart Institute and the UT Health Science Center at Houston2, Baylor College of Medicine3 and Rice University

Suncica Canic1, Roland Glowinski1, Tsorng-When Pan1, Doreen Rosenstrauch2, Craig Hartley3 (PIs) DMS-0443826 (UH), DMS-0443549(THI), DMS-0443563(Baylor) www.math.uh.edu/~canic/NIGMS.html

RESULTS: Coronary artery disease causes narrowing or stenosis of coronary arteries which might lead to heart attack. Treatment of coronary artery disease involves inserting a vascular stent into the diseased artery to keep the artery open thereby securing blood supply to the heart muscle.

Upon implantation, vascular stents have been shown to activate inflammatory responses due to their poor biocompatibility. To improve biocompatibility of implantable cardiovascular devices, our group showed that lining stents with ear cartilage cells called auricular chondrocytes, might produce a long-lasting biocompatible device. Chondrocytes were genetically modified to produce nitric oxide which is known to have an anti-inflammatory action. They were shown to exhibit superior adherance to artificial surfaces such as those of stents, shown in Figure 2.

Figure 2. Stent struts lined with auricular chondrocytes: before expansion of stent (left), after expansion (right) (Wire filament width is 200 microns).

Figure 1. Vascular stentand restenosis. (Click onthe picture to run the movie.)

METHODS: To investigate and optimize coating of stents by auricular chondrocytes we have been working on the development of a fluid-structure-cell interaction algorithm. The aim is to mathematically and computationally simulate the growth, adhesion, detachment and long-term behavior of auricular chondrocytes under controlled flow conditions. Two algorithms: a fluid-structure interaction algorithm (Figure 3 top) and an algorithm simulating cell deposition and attachment to artificial surfaces (Figure 3 bottom) have already been developed, and a comparison with experiment showed good agreement.

WHY IT MATTERS: Heart attack is the single leading cause of death in the United States. Design of long-lasting biocompatible stents used in the treatment of coronary artery disease might lower the heart attack rates and improve the health of heart patients.

Figure 3 Computational simulation:blood flow-stent interaction (top), cell rolling and detachment (bottom). (Click on the picture to run the movies.)

Collaborative Research: Modeling the Growth and Adhesion of Collaborative Research: Modeling the Growth and Adhesion of Auricular Chondrocytes under Controlled Flow ConditionsAuricular Chondrocytes under Controlled Flow Conditions

Figure 4.. Experimental flow-loop set up.

PUBLICATIONS (selected): For a complete list of publications please visit www.math.uh.edu/~canic/NIGMS.html

• S. Canic, J. Tambaca, G. Guidoboni, A. Mikelic, C.J. Hartley, D. Rosenstrauch. Modeling viscoelastic behavior of arterial walls and their interaction with pulsatile blood flow. SIAM J Applied Mathematics Vol. 67 (2006).

• R. Glowinski, G. Guidoboni, T-W Pan, "Wall-driven incompressible viscous flow in a two-dimensional semi-circular cavity", Journal of Computational Physics. To appear (2006).

• S. Canic, C.J. Hartley, D. Rosenstrauch, J. Tambaca, G. Guidoboni, A. Mikelic. Blood Flow in Compliant Arteries: An Effective Viscoelastic Reduced Model, Numerics and Experimental Validation. Annals of Biomedical Engineering. 34 (2006), pp. 575 – 592.

• S. Canic, Z. Krajcer, and S. Lapin. Design of Optimal Prostheses Using Mathematical Modeling. Endovascular Today (Cover Story). (2006) 48-50.

•T.-W. Pan and R. Glowinski, Numerical Simulation of Pattern Formation in a Rotating Suspension of non-Brownian Settling Particles, in Free and Moving Boundaries: Analysis, Simulation and Control, Glowinski and Zolesio eds., Lecture Notes in Pure and Applied Mathematics, Vol. 252, Taylor & Francis/CRC Press, Boca Raton, FL, 2006 .

•S. Canic, A. Mikelic and J. Tambaca. A two-dimensional effective model describing fluid-structure interaction in blood flow: analysis, simulation and experimental validation Comptes Rendus Mechanique Acad. Sci. Paris 333(12) 867-883. (2005).

OUTLOOK: Although a first generation fluid-structure interaction algorithm and a fluid-cell interaction algorithm have been developed by our group, the coupling between the two algorithms is yet to be investigated. Simultaneously, we have been working on the set up of the flow loop, shown in Figure 4, for experimental testing of the vascular stent dynamics and cell slough off under controlled (pulsatile) flow conditions. The flow loop will be used to validate the mathematical and computational algorithm. Once the computational algorithm is experimentally validated, it will be used as a guide to optimal design of coated stents allowing different stent geometries and different artificial surfaces.

*Received US Congressional Recognition forThe Best Women in Technology Award (Houston 2005)(awarded to PI Canic)*SIAM 2004 von Karman Prize (awarded to Glowinski)*Glowinski elected to the French National Academy ofSciences in 2005

PIs, Collaborators and Students: S. Canic, T.-W. Pan, R. Glowinski (UH), D. Rosenstrauch (UTMCH&THI), C. Hartley (Baylor) PIs; G. Guidoboni (UH), A. Mikelic (France), J. Tambaca (Croatia), D. Mirkovic (MD Anderson Cancer Center), Z. Krajcer (THI), S. Lapin (UH) Collaborators; M. Kosor, T. Kim, J. Hao, T. Wang, B. Stanley (UH), K. Moncivais,

T. Joseph, J. Gill (Rice) Students.

Thanks: Mia Mirkovic for help with poster.