1. Academic Validation
  2. Vascular stent with immobilized anti-inflammatory chemerin 15 peptides mitigates neointimal hyperplasia and accelerates vascular healing

Vascular stent with immobilized anti-inflammatory chemerin 15 peptides mitigates neointimal hyperplasia and accelerates vascular healing

  • Acta Biomater. 2024 Feb 19:S1742-7061(24)00090-4. doi: 10.1016/j.actbio.2024.02.022.
Lan Wen 1 Hua Qiu 2 Shuang Li 3 Yan Huang 3 Qiufen Tu 4 Nan Lyu 4 Xiaohui Mou 4 Xia Luo 3 Jinyu Zhou 1 Yin Chen 5 Chaohua Wang 6 Nan Huang 7 Jianguo Xu 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610065, China.
  • 2 Stomatologic Hospital and College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, China.
  • 3 Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
  • 4 Key Laboratory of Advanced Technology of Materials of Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
  • 5 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 511436, China.
  • 6 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610065, China. Electronic address: neuro_chaohua_wang@163.com.
  • 7 Key Laboratory of Advanced Technology of Materials of Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: huangnan1956@163.com.
  • 8 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610065, China. Electronic address: xujg@scu.edu.cn.
Abstract

Endovascular stenting is a safer alternative to open surgery for use in treating cerebral arterial stenosis and significantly reduces the recurrence of ischemic stroke, but the widely used bare-metal stents (BMSs) often result in in-stent restenosis (ISR). Although evidence suggests that drug-eluting stents are superior to BMSs in the short term, their long-term performances remain unknown. Herein, we propose a potential vascular stent modified by immobilizing clickable chemerin 15 (C15) Peptides on the stent surface to suppress coagulation and restenosis. Various characterization techniques and an animal model were used to evaluate the surface properties of the modified stents and their effects on endothelial injury, platelet adhesion, and inflammation. The C15-immobilized stent could prevent restenosis by minimizing endothelial injury, promoting physiological healing, restraining the platelet-leukocyte-related inflammatory response, and inhibiting vascular smooth muscle cell proliferation and migration. Furthermore, in vivo studies demonstrated that the C15-immobilized stent mitigated inflammation, suppressed neointimal hyperplasia, and accelerated endothelial restoration. The use of surface-modified, anti-inflammatory, endothelium-friendly stents may be of benefit to patients with arterial stenosis. STATEMENT OF SIGNIFICANCE: Endovascular stenting is increasingly used for cerebral arterial stenosis treatment, aiming to prevent and treat ischemic stroke. But an important accompanying complication is in-stent restenosis (ISR). Persistent inflammation has been established as a hallmark of ISR and anti-inflammation strategies in stent modification proved effective. Chemerin 15, an inflammatory resolution mediator with 15-aa peptide, was active at picomolar through cell surface receptor, no need to permeate cell membrane and involved in resolution of inflammation by inhibiting inflammatory cells adhesion, modulating macrophage polarization into protective phenotype, and reducing inflammatory factors release. The implications of this study are that C15 immobilized stent favors inflammation resolution and rapid re-endothelialization, and exhibits an inhibitory role of restenosis. As such, it helps the decreased incidence of ISR.

Keywords

chemerin 15 peptide; click chemistry; in-stent restenosis; inflammation regulation; vascular stent.

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