A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts

Tianshu Chu; Qingye Li; Chun Dai; Xiang Li; Xiang Kong; Yangming Fan; Hongyan Yin; Jianjun Ge

doi:10.1016/j.bioactmat.2022.10.013

A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts

Bioact Mater. 2022 Oct 25:22:466-481. doi: 10.1016/j.bioactmat.2022.10.013. eCollection 2023 Apr.

Authors

Tianshu Chu^{1

2}, Qingye Li³, Chun Dai^{1

2}, Xiang Li⁴, Xiang Kong^{1

2}, Yangming Fan^{1

2}, Hongyan Yin¹, Jianjun Ge^{1

2}

Affiliations

¹ Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
² Anhui Provincial Engineering Research Center for Cardiopulmonary and Vascular Materials, Hefei, Anhui, 230001, China.
³ College of Food Science, Sichuan Agricultural University, No.46, Xin Kang Road, Yaan, Sichuan Province, 625014, PR China.
⁴ CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

Abstract

Vein grafts are widely used for coronary artery bypass grafting and hemodialysis access, but restenosis remains the "Achilles' heel" of these treatments. An extravascular stent is one wrapped around the vein graft and provides mechanical strength; it can buffer high arterial pressure and secondary vascular dilation of the vein to prevent restenosis. In this study, we developed a novel Nanocellulose-gelatin hydrogel, loaded with the drug Astragaloside IV (AS-IV) as an extravascular scaffold to investigate its ability to reduce restenosis. We found that the excellent physical and chemical properties of the drug AS-IV loaded Nanocellulose-gelatin hydrogel external stent limit graft vein expansion and make the stent biocompatible. We also found it can prevent restenosis by resisting endothelial-to-mesenchymal transition (EndMT) in vitro. It does so by activating autophagy, and AS-IV can enhance this effect both in vivo and in vitro. This study has added to existing research on the mechanism of extravascular stents in preventing restenosis of grafted veins. Furthermore, we have developed a novel extravascular stent for the prevention and treatment of restenosis. This will help optimize the clinical treatment plan of external stents and improve the prognosis in patients with vein grafts.

Keywords: EndMT; Extravascular stent; NC-Gelatin hydrogel; Restenosis; Vein graft.