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Hybrid Electrospun Rapamycin-Loaded Small-Diameter Decellurized Vascular Grafts Effectively Inhibit Intimal Hyperplasia

28 Pages Posted: 12 Apr 2019 First Look: Accepted

See all articles by Yang Yang

Yang Yang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Dong Le

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Huanxue Zou

Yuyao People's Hospital, Department of Cardiology

Shixing Huang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Qi Yang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Sen Li

Zhejiang University - Department of Vascular Surgery

Feng-Ling Qing

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Xiaofeng Ye

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Zhengwei You

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology; Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials

Qiang Zhao

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Abstract

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular disease, there is a significant demand for small diameter (inner diameter < 6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aortas (DRA). However, histological assessments of the grafts revealed development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of the grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellurized vascular graft to fabricate an RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with drug delivery function to prevent intimal hyperplasia. The RM-HTEV possessed superior mechanical properties over DRA and exhibited sustained drug release profile. In order to evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was operated on rats. Doppler-sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of the explanted grafts 12 weeks post-implantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV group, without impairing re-endothelialization and M2 macrophage polarization. Overall, RM-HTEV offers a promising strategy for developing small-diameter vascular grafts with great clinical translational potential.

Keywords: polycaprolactone, electrospin, rapamycin, intimal hyperplasia, vascular graft

Suggested Citation

Yang, Yang and Le, Dong and Zou, Huanxue and Huang, Shixing and Yang, Qi and Li, Sen and Qing, Feng-Ling and Ye, Xiaofeng and You, Zhengwei and Zhao, Qiang, Hybrid Electrospun Rapamycin-Loaded Small-Diameter Decellurized Vascular Grafts Effectively Inhibit Intimal Hyperplasia (April 8, 2019). Available at SSRN: https://ssrn.com/abstract=3368397

Yang Yang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Shanghai
China

Dong Le

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Shanghai
China

Huanxue Zou

Yuyao People's Hospital, Department of Cardiology

Yuyao
China

Shixing Huang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Shanghai
China

Qi Yang

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery

Shanghai
China

Sen Li

Zhejiang University - Department of Vascular Surgery

Zhejiang
China

Feng-Ling Qing

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Shanghai
China

Xiaofeng Ye

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery ( email )

Shanghai
China

Zhengwei You

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology ( email )

Shanghai
China

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials ( email )

Shanghai
China

Qiang Zhao (Contact Author)

Shanghai Jiao Tong University (SJTU) - Department of Cardiac Surgery ( email )

Shanghai
China

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