Vascular implants can cause inflammatory reactions, such as restenosis and thrombosis, inside the body. The implants cause endothelial cells (which line the inside of blood vessels) to grow in number and the cells begin to "stick" to the surface of the devices. Restenosis happens when vascular smooth muscle cells (VSMCs), which surround the endothelial layer in cells, proliferate. Thrombosis is caused by proliferation of the endothelial cells themselves.

One way to overcome these problems is to use drug-eluting stents that inhibit VSMC growth, but such devices can cause thrombosis later on. Ideally, a stent should not prevent endothelial cells from moving about, and at the same time stop the growth of VSMCs. A team led by Tejal Desai of UCSF has now found that stents made from TiO2 nanotubes might just be the ticket.

Ideal for vascular implants
Earlier studies have shown that TiO2 nanotube arrays could make ideal coatings for vascular implants, such as stents and grafts. Titanium is already widely used in hip and dental implants and is biocompatible because it spontaneously forms a protective oxide layer at its surface. What's more, researchers can routinely grow highly ordered, vertical TiO2 nanotubes from a titanium surface through a simple electrochemical process. These tubes have diameters between 22 and 300 nm and their size can be precisely controlled, which allows feature sizes similar to those of cell receptors or proteins to be fabricated.

Desai and colleagues used a microarray analysis to compare how primary vascular cells grow on the flat nanotube surfaces. "The whole genome microarray allowed us to look at mRNA transcription levels of all of the human genes in the genome," team member Lily Peng told "We then analysed this data to determine what likely effect this would have on vascular cell behaviour."

Optimal response

The results suggest that TiO2 nanotubes encourage endothelial cells to travel while inhibiting VSMC growth. "This is the optimal type of response we would want from vascular cells in response to implants, like stents," added Peng.

In addition to these results, the researchers also identified the networks that might be involved in this response. Identifying such networks will be important for understanding how cells sense and react to different nanostructures in the body, and how these interactions could be used to improve medical device design.

The team now plans to further elucidate the mechanism behind how cells sense different nanoarchitectures. "We will also perform in vivo studies of how nano-topographical surfaces might affect vascular device performance in animal models," revealed Peng.

The work was published in Nano Letters.