Image Source: MIV Therapeutics

Washington, DC—Maurice Buchbinder, MD, director of the Foundation for Cardiovascular Medicine in La Jolla, Calif., opened a lecture at CRT 2009 by asking, “Why do we need biodegradable stents? What we know about metallic stents is so complete and polished, why should we start all over again and try to define a new prosthesis that goes away?”

The rhetorical question was followed by a concrete answer. “With the prosthesis disappearing, perhaps we will have less adverse events, particularly less stent thrombosis. Perhaps we will also have less product inflammation, which participates in the formation of neointimal hyperplasia, or less stent fractures, which might be associated with restenosis. More importantly, we think biodegradable stents won’t restrict arterial remodeling, which some data suggest.” 

Secondarily, biodegradable stents would permit imaging by CT angiography, which is typically hindered by metallic blooming artifacts, and perhaps could permit CABG surgery if the stent fails, he said.  

There are various groups of polymers available for biodegradable stents, including:

• PLA (polylactic acid), used in the first-in-man biodegradable stent (Igaki-Tamai) in the early 2000s, and used in Abbott Vascular’s current BVS biodegradable stent;
• Tyrosine polycarbonate, used in Boston Scientific’s REVA biodegradable stent; and
• A magnesium alloy, used in a product from Biotronik, the only metallic biodegradable stent.

Biodegradable polymers, like many processes in the body, are subject to the Krebs cycle; they are digested and become byproducts. This is a gradual process and the timing of stent erosion is critical toward its success, Buchbinder said.  

“To understand biodegradable stents, one has to understand the period in which they degrade,” he said, “which can be a few months to a few years.” 

The challenges for developing the optimal biodegradable stent are formidable, he said, and include:

• Tailoring the rate of degradation to minimize the byproduct and the inflammation around the byproducts;
• Optimizing biocompatibility;
• Having the scaffolding hold up long enough to minimize recoil of the vessel;
• Knowing what happens to any remaining polymer perhaps in some formulations;
• Optimally adding drugs to the biodegradable polymer backbone; and
• Making sure there are some types of permanent markers for imaging purposes.

Studies with the first-in-man biodegradable stent in 2002, the Igaki-Tamai, a non-drug-eluting stent (DES), found no unusual findings when compared to bare-metal stents in 64 patients, Buchbinder said. Researchers discovered that immediately after stent implantation, the lumen got larger but recoiled a bit as the device started to disappear. At about 36 months, lumen size increased by approximately 2.2 mm. (This stent was ultimately abandoned.) 

Two-year follow-up data from the ABSORB trial—which is looking at the BVS tubular biodegradable DES from Abbott—showed a binary restenosis rate of 11 percent in 27 patients, “an impressive number out of the chute,” Buchbinder said. 

It wasn’t neointimal hyperplasia that caused the restenosis rate, however, but rather stent loss because the stent recoiled due to insufficient scaffolding, ultimately causing a decrease in lumen diameter, he said.  

The REVA stent used a slide-and-lock design to give it more radial strength. Laboratory tests showed very good recoil, flexibility and visibility on MR, CT and x-ray. Human trials were put on hold, however, because the interlocks were the first part of the stent to begin to erode, thereby causing scaffolding integrity issues, Buchbinder said.  

Human trials with the Biotronik magnesium alloy stent also were stopped because the scaffolding integrity was compromised by the degradation process. 

A biodegradable stent in testing from BTI uses a combination of drugs and anti-inflammatory agents and has tested well. “At least on the bench, there is degradation at one and three months, and ultimately between six and nine months the device disappears,” he said. “In animal testing, angiographic results have shown good radial strength and a low restenosis rate. 

“Biodegradable polymer stents seem to be the ultimate candidate for the ideal stent. Further evaluation is still needed to understand their role as a as substitute for bare-metal stents or present generation metallic drug-eluting stents,” Buchbinder concluded.