Compared with traditional permanent metal stents, biodegradable stents are made of biodegradable or absorbable materials and have good histocompatibility and biodegradability. It can effectively dilate blood vessels in the early stage, and can be gradually degraded, and the degradation products can be eliminated from the body through metabolism or absorbed and utilized by the human body without affecting the long-term vascular function.

Existing degradable stents mainly include metal degradable stents (including magnesium alloy metal stents and degradable iron metal stents) and polymer degradable stents (including polylactic acid, polyanhydride, polycarbonate, etc., among which L-polylactic acid (PLLA) is the main).

Degradable magnesium alloy stent

Magnesium alloy stents (AMS) are usually made of 97% magnesium metal and 7% other metals by mass ratio, similar to traditional metal stents, magnesium alloy stents can provide sufficient radial support, which is not easy to occur after implantation Early elastic retraction. Compared with polymer stents, magnesium metal stents are thinner and have good ductility, and will not cause stent fracture due to expansion. Moreover, magnesium alloy stents have good histocompatibility. After implantation, stents undergo rapid endothelialization, and negative potential is generated during the degradation process, which can inhibit thrombosis. The degradation products are inorganic salts, which only cause a weak inflammatory response. The stent is completely After degradation, the original vascular function can be restored.

The experimental results of the first-generation degradable AMS-1 were not satisfactory. By refining the alloy, the degradation rate of the second-generation magnesium alloy stents was slowed down to 2-3 times of the original, and the scaffold skeleton was about 30% thinner than that of the first-generation stent. Subsequently, the first-generation drug-coated degradable magnesium alloy stent (DREAMS-1) with the addition of polylactic-co-glycolic acid (PLGA) polymer and paclitaxel coating treatment on the surface appeared. The second-generation DREAMS (DREAMS-2) uses polylactic acid polymer as a carrier, and uses sirolimus as an anti-proliferative drug coating, with a scaffold of 150 μm. DREAMS-2 is currently in the experimental verification stage.

High molecular polymer degradable stent

The polymer degradable stents are dominated by L-polylactic acid (PLLA) polymer stents. PLLA is a thermoplastic aliphatic polymer, which can be degraded into lactic acid through its own catalytic hydrolysis, and finally metabolized into water and carbon dioxide in the tricarboxylic acid cycle. PLLA improves the radial support force by combining semi-crystalline polymers, and combining with amorphous polymers, the coating drug can be uniformly dispersed within a predetermined time and the stent can be uniformly degraded. The duration of the degradation process generally ranges from 2 to 4 years.

Compared with conventional metal stents, theoretically, PLLA needs to be 2.4 times thicker than metal stents to provide the same radial support force. The elastic recoil rate of the Abbott stent is 16.6%, which is enough to prove the fact that its radial support force is insufficient.

1

Igaki-Tamai stand

The Igaki-Tamai stent is the first non-drug-coated biodegradable stent made of PLLA for clinical evaluation in humans, with a stent skeleton of 170 μm. Clinical follow-up found that the stent was completely degraded within 36 months. The Igaki-Tamai stent is thermoplastic, it requires an 8F sheath to be delivered to a specific location, balloon dilatation, contrast heating to 80 °C, and then auto-expanding within 30 min under the effect of body temperature. It is reported that Nishio et al treated 50 patients with Igaki-Tamai stent (the number of lesions was 63, and 83 stents were applied). After 10 years of follow-up, they found that the PLLA stent was completely absorbed within 3 years. The TLR rate after 10 years was 28%.

The Igaki-Tamai stent had a 34% loss of maximum lumen diameter at 6 months, but 21% expansion over the subsequent 3 years. The maximum lumen area assessed by intravascular ultrasound was 5.44 mm2, and the lumen area decreased to 3.64 mm2 6 months after stent implantation in the diseased segment, and increased to 5.18 mm2 in the following 3 years. These data indicate that the blood vessels can be remodeled well after the stent is completely degraded and absorbed in the late stage. Despite these promising results, and the possibility of further TLR reduction by adding an antiproliferative drug, the use of high-temperature contrast agents in the coronary arteries has prevented this stent from becoming mainstream.

2

Abbott bracket

The Abbott stent is the most widely studied degradable drug-eluting stent. The first-generation Abbott stent (BVS 1.0) is made of PLLA polymer, with a stent backbone thickness of about 150 μm and a surface coating of everolimus. A 30-patient multicenter human trial evaluating BVS 1.0 (single 3.0 mm × 12.0 mm or 3.0 mm × 18.0 mm stent) in coronary arteries with symptomatic angina or asymptomatic ischemia found 6 follow-up The late caliber loss of the vascular segment covered by the stent reached 0.44 mm (11.8%) at month, and the elastic recoil of the stent was obvious after implantation, which proved the defect of insufficient radial support force of the stent. The overall MACE rate at five-year follow-up was 3.4% (including one uncomplicated non-Q-wave myocardial infarction within the first 6 months).

The second-generation Abbott stent (BVS 1.1) is based on BVS 1.0 with corresponding design changes to improve radial support and increase stent coverage, making the delivery system easier to maneuver and store at room temperature.

3

Reva stand

The Reva stent is a tyrosine-derived polycarbonate polymer stent infused with radiopaque iodine for labeling. It is a balloon-expandable stent that, when fully expanded, covers 55% of the arterial wall. The first clinical trial in humans by Pollman et al reported a high clinical event rate for the stent: TLR 67%. This is mainly due to insufficient expansion of the stent within the vessel.

As a result, the Reva stent was redesigned to produce a new generation ReZolve stent with a higher strength polymer, a sirolimus surface coating, and novel sliding and helical locking. Clinical evaluation of this new stent began in December 2011: 100% clinical procedural success, 0 MACE events at 3 months. However, the sheath delivery mechanism of this stent limits its application in small vessels and vessels with greater curvature. Then came the brand new ReZolve 2 stent (6F), a sheathless delivery system with a reinforced polymer itself that increased radial support by 30%. The ReZolve 2 stent was initiated in the global multicenter trial of RESTORE II (enrollment started in 2013).

4

IDEAL Bracket

The IDEAL scaffold is mechanically supported by the polymer backbone of polylactic acid anhydrite and sebacic acid salicylic acid trimer, salicylic acid-adipate salicylic acid trimer as a carrier and sirolimus coating. An additional coating of salicylic acid was found to reduce inflammatory responses in animal studies36. This may outperform conventional polymers. Jabara et al demonstrated the safety of the first-generation IDEAL stent in the Whisper trial (n=11): no early elastic recoil. However, probably because the dose of sirolimus was insufficient and the duration of drug release was too short, the stent-covered segmental vessels had significant intimal growth.

The second-generation IDEAL stent increases the dose of the stent-coated drug, slows the drug release rate, and makes it more compatible. Specific clinical data for this stent are still in the trial.

Outlook

The use of biodegradable materials in stents is of epoch-making significance.

However, the degradation time of degradable stents lacks an exact standard. If the degradation time is too short, elastic retraction may occur, resulting in a greatly increased probability of stenosis. If the degradation time is too long, the intimal hyperplasia in the stent may be excessive, and the possibility of stent thrombosis will also increase. Degradable stents coated with drugs can inhibit intimal hyperplasia, but a balance point still needs to be found between the release rate and duration of the drug and the degradation rate of the stent. Otherwise, the promotion of degradable stents may still be limited.

After the degradable stent is completely absorbed, compared with the permanent metal stent, it eliminates the continuous stimulation to the vascular wall, whether it can truly restore the vascular integrity and vasomotor function, and whether it allows multiple stent implantation treatment, and also It will be one of the directions of future research.

In addition, the positioning of the degradable stent after implantation may also be a problem, because the degradable polymer stent is X-ray transparent and has no clear markers, which brings difficulties to the positioning of the stent, and also brings difficulties to the postoperative imaging follow-up. inconvenient. Whether the existence time after adding the marker will affect the stability of the scaffold needs further verification.

With the development of science and technology, these problems will be properly solved, so that degradable stents will have a bigger stage in vascular interventional therapy.