Drug Wrap Could Prevent Stent Scarring

University of California, San Francisco

Each year, more than a half-million Americans undergo stenting procedures to have a narrowed coronary artery propped open. The procedure helps to restore blood flow and is common for certain patients who’ve experienced a heart attack or other arterial blockages.

Fig. 1 – Kevin Lance, a graduate student in Tejal Desai’s lab, holds up a tiny “wrap” that could be placed around an artery or vein and slowly release a fish oil-derived drug to prevent vascular scarring. (Credit: Kathleen Masterson, UCSF)

However, in about 25 percent of these cases, the vasculature tissue begins to narrow again after the procedure, in effect, regrowing the blockage. The problem of excessive vascular scarring isn’t limited to stents, it can affect many other common procedures such as angioplasty, bypass surgery, and placement of fistulas or grafts for patients on dialysis.

“When we operate on an artery it always causes an inflammatory reaction and a subsequent scarring response just like anywhere else on your body, even the skin,” said Michael S. Conte, MD, chief of Vascular & Endovascular Surgery at University of California, San Francisco (UCSF).

If this inflammation continues, the cells surrounding the tiny metal cage still treat the area as injured, and ultimately grow back in.

But, say researchers at UCSF, a common class of molecules from fish oil could change all that. When the body heals naturally, it’s a two-step process. First, it generates compounds to promote inflammation, then the body sends in a second set of compounds that actively stops inflammation.

These anti-inflammation signaling compounds are derived in the body from dietary fish oil, and Conte and collaborators Charles Serhan of Harvard University and Tejal Desai, PhD, chair of the UCSF Department of Bioengineering and Therapeutic Sciences, are using them to develop treatments to prevent ongoing inflammation in blood vessels.

Desai has been working on stents from a different angle; her lab at the School of Pharmacy focuses on therapeutic microtechnology and nanotechnology. If successful, their collaboration could help prevent arteries and veins from closing up again after surgeries, such as a stent implant or an angioplasty, a procedure where a balloon is temporarily inserted into the artery or vein to open it up.

Conte and Desai won an NIH grant that specifically funds promising vascular research that could be translated into a medicinal use. So far, they have shown that the drug reduces vascular scarring in mice and rabbits after they undergo an angioplasty, they also found a reduced number of white cells weeks later, which suggests healing was accelerated. Their next challenge is to get the biolipid drug to the injured area, and to control its release slowly over time.

Desai’s team is working on the next step by building stents with unique geometric surfaces that can actually reduce scarring and re-blockage because of its surface texture alone. That’s because certain geometric patterns can encourage or discourage cells from sticking to them. In the case of a stent, the goal is to create a nanotextured surface that repels the smooth muscle cells, keeping them from growing on its surface. Not only that, but Desai is finding that this unique surface, which looks a bit like nano-sized coral, also naturally absorbs the biolipid drug.

This means that no artificial carrier chemicals are required to load the stent with the lipid drug. And so far, it appears that because the nano-tubes are so small, the drug effectively takes days to weeks to leach out into the body, which could be fairly aligned with the ideal rate of delivery.

Desai’s lab is also developing a thin film or “wrap” as another possible method of delivering the biolipid drug to an injured vein or artery. It looks a piece of plastic wrap about the size of an infant’s fingernail, and it’s designed to wrap around the injured vessel like a hot dog bun, and deliver the drug through the vessel wall. (See Figure 1)

“The interesting thing about this is that it’s a biodegradable wrap, so it sits on the outside, delivers the drug, and then disappears, versus the stent which is something that’s going to stay there permanently,” said Desai. She says that this new combination drug-device approach has implications for all kinds of vascular surgeries throughout the body.