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Acta Biomater. 2019 Oct 1;97:321-332. doi: 10.1016/j.actbio.2019.06.037. Epub 2019 Sep 12.

Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia.

Author information

1
Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
2
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
3
Department of Cardiology, Yuyao People's Hospital, Yuyao, Zhejiang 315400, China.
4
Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
5
Department of Vascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
6
Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Electronic address: xiaofengye@hotmail.com.
7
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China. Electronic address: zyou@dhu.edu.cn.
8
Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Electronic address: zq11607@rjh.com.cn.

Abstract

For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is 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 aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEV in vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeks in vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential. STATEMENT OF SIGNIFICANCE: In this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. In in vivo implantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.

KEYWORDS:

Electrospin; Intimal hyperplasia; Polycaprolactone; Rapamycin; Vascular graft

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