Introduction

Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of vascular devices such as stents and left ventricular assist devices (LVADs). Cardiovascular devices have been shown to be associated with thromboembolism, bleeding and infection, which are characteristics of poor biocompatibility [2]. To improve the biocompatibility of stents and LVADs whose artificial surfaces will be contacting the blood stream, endothelial cells or genetically engineered smooth muscle cells might be an optimal lining. Endothelial cells secrete, among others factors, chemotactic, growth, and nonthrombogenic factors such as prostacycline and nitric oxide (NO). Nitric oxide, a small gaseous molecule, is known to play a role in vasodilatation, smooth muscle relaxation, programmed cell death, inflammation, the immune system, and in the inhibition of platelet adhesion, aggregation, and activation. There are drawbacks, however, to using either endothelial cells or smooth muscle cells to line cardiovascular devices. Neither cell type is abundantly available nor easily accessible, harvested, or isolated. Moreover, endothelial cells have been observed to slough off easily from artificial surfaces, see [4].

In the search for an alternative cell source, our group has begun investigating the ability of autologous auricular chondrocytes, i.e., ear cartilage cells, to form a strong adherent lining on artificial surfaces of stents. Auricular cartilage harvested from the ear is abundantly available and easily accessible. Auricular chondrocytes have been shown to provide a strong adherent cell lining for left ventricular assist devices because of their ability to synthesize strong adherent extracellular matrix proteins [6]. See Figure 1.1.

Figure: Immunocythochemistry of passaged chondrocytes in a cell culture medium supplemented with vitamin C for improved collagen synthesis (left); Scanning electron microscopy of the implanted LVAD biomaterial surface after 7 days of implantation in vivo. An extensive amount of extracellular matrix and an intact, well-incorporated cellular coating were noted on the textured polyurethane (middle) and sintered titanium (right) surfaces. (Scott-Burder, Rosenstrauch et al. [6].)

Moreover, Rosenstrauch et al. have shown that it is possible to genetically engineer auricular chondrocytes to produce antithrombogenic factors (e.g., nitric oxide, prostacycline) by using an e-green fluorescent protein (e-GFP) as control and an e-NOS construct in vitro [7]. This is a break-through discovery because seeding genetically engineered auricular chondrocytes onto artificial surfaces would result in the desired combination of tissue availability, strong surface adhesion, effective production of antithrombogenic factors and increased possibility of healing. Stents covered with genetically engineered auricular chondrocytes might lower the restenosis rates and provide a long-lasting biocompatible prosthesis.

Figure: Day 8: Auricular Chondrocytes Coverage of Wallstent Stent (magnification 1000X; wire width 200 micrometers.) Results by D. Rosenstrauch MD, B. Magesa, M. Ng, D. Paniagua MD, OH Frazier MD, D. Fish MD.

We have recently begun producing a coronary stent lined with chondrocytes. Chondrocytes are naturally nourished by diffusion and produce substantial amounts of extracellular matrix components which seem to cover the small pores in the stent and extend between the struts showing inclination for complete prosthesis coverage, see Figure 1.2.

To optimize the process of lining of artificial surfaces with auricular cartilage, it is useful to understand how initial cell count, proximity to other cells, and the type of artificial surface affect the rate of cell division and growth of extracellular matrix. In this vein, we designed a mathematical model that explores these issues and provides chondrocyte proliferation and accumulation of the extracellular matrix as a function of time.