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Clinical and research medicine: Interventional cardiology
e0473 Rapid re-endothelialization and anti-intimal hyperplasia coronary stent system with a novel biomacromolecular prohealing coating
  1. Shen Li,
  2. Yang Wei,
  3. Zhong Wei,
  4. Tian Wenjie,
  5. Tang Jingliang,
  6. Wu Yizhe
  1. Shanghai Institute of Cardiovascular Diseases and Cardiology Department, Zhongshan Hospital, Shanghai, China


Background Rapid healing of endothelium on the coronary stent is a crucial method to prevent late stent thrombosis, a rare but life-threatening complication of drug eluting stents (DES). Here we developed a novel biomacromolecular coating for pro-healing DES and investigated their anti-proliferation as well as re- endothelialisation function.

Methods A dual function DES was designed in an asymmetric coating way: a layer-by-layer (LBL) self-assembly polymer of chitosan/heparin (CS/HEP) coated onto aluminal side of stents to accelerate re-endothelialisation and sirolimus onto vessel wall side to inhibit neointimal hyperplasia. Morphological, gene transcript (RT-PCR), endothelial and antithrombotic marker expression analyses were used to evaluate the effects of CS/HEP coating on adhesion, proliferation and differentiation of CD133+ endothelial progenitor cells (EPCs). Finally, the prohealing function as well as impact on coronary stenosis of this stent system were assessed in porcine model.

Results CS/HEP coating can significantly promote the adhesion, proliferation and differentiation of EPCs in vitro. CS/HEP upregulated expression of endothelial marker (ie, PECAM-1 and eNOS) and antithrombotic factor (ie, thrombomodulin). Interestingly, CS/HEP also promoted down-regulation of sirtuin-1, a gene related with endothelial cellular senescence. In porcine model, CS/HEP modified sirolimus eluting stent (CH-SES) showed rapid endothelialization superiority to bare metal stent (BMS) and SES, even in 1 week after stent implantation. Through electron microscopy analysis, the arteries treated with CH-SES were mostly fully endothelialized. As for effects on intimal hyperplasia, by angiography, intravascular ultrasound and histomorphometric analysis, there was no significant difference between CH-SES and SES in intimal thickness from 1 month to 3 and 6 months. Generally, SES took at least 3–4 weeks for the endothelial coverage of the stent struts, while the CH -SES only took 1–2 weeks for endothelial repair and kept antiproliferation function as SES.

Conclusion This natural chitosan/heparin biomacromolecular self-assembly coating was safe and efficient in stent implanted porcine model. The preliminary results hinted possible molecular basis of CS/HEP for rapid endothelial recovery. Meanwhile, coated with heparin, the CS -SES showed potent anti-coagulation function compared to traditional SES. To sum up, CS -SES may represent a promising self-rapid healing DES system to prevent in stent thrombosis as well as restenosis.

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