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SCIENCE CHINA Life Sciences, Volume 61 , Issue 10 : 1178-1188(2018) https://doi.org/10.1007/s11427-018-9348-9

Construction of a small-caliber tissue-engineered blood vessel using icariin-loaded β-cyclodextrin sulfate for in situ anticoagulation and endothelialization

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  • ReceivedApr 21, 2018
  • AcceptedJun 7, 2018
  • PublishedAug 27, 2018

Abstract

The rapid endothelialization of tissue-engineered blood vessels (TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases. β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells (RAVECs). Subsequently, we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy (SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.


Funded by

the National Science Fund for Distinguished Young Scholars(31625011)

the National Key Research and Development Program(2016YFC1101100)

the National Key Research and Development Plan Young Scientists Program(2017YFA0106000)

and the Young Elite Scientists Sponsorship Program by Cast(YESS20160180)


Acknowledgment

This work was supported by the National Science Fund for Distinguished Young Scholars (31625011), the National Key Research and Development Program (2016YFC1101100), the National Key Research and Development Plan Young Scientists Program (2017YFA0106000) and the Young Elite Scientists Sponsorship Program by Cast (YESS20160180).


Interest statement

The author(s) declare that they have no conflict of interest. These studies conformed with the Helsinki Declaration of 1975 (as revised in 2008) concerning Human and Animal Rights, and we followed the policy concerning Informed Consent, as shown on Springer.com.


Supplement

SUPPORTING INFORMATION

Figure S1 The release curve and stability of icariin.

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    (Color online) Construction of small-caliber TEBVs using icariin-loaded sulfated sodium salt of β-cyclodextrin. A, The chemical structure of Icariin. B, The spatial structure of sulfated sodium salt of β-cyclodextrin. C, Sulfated sodium salt of β-cyclodextrin can load and release drugs. D, Small-caliber TEBVs was modified by icariin-loaded sulfated sodium salt of β-cyclodextrin through electrostatic interaction.

  • Figure 2

    Icariin can promote the proliferation and migration of EPCs and migration of RAVECs. A, CCK8 assay was used to detect toxicity of different dosage of icariin after co-cultured with EPCs for 48 h. &, P<0.05 versus 15 µmol L−1 icariin-treated group. B, CCK8 assay showed the A value (450 nm) of EPCs cultured for 48 h in each group. C and E, The cell scratch experiment was applied to show the healing of the RAVEC scratches in each group. D and F, Transwell experiment was applied to show the function of icariin to promote EPC migration in each group. **, P<0.01.

  • Figure 3

    The characteristics of icariin-loaded sulfated sodium salt of β-cyclodextrin and the TEBVs that it modified. A, The IR spectra of sulfated sodium salt of β-cyclodextrin and icariin-loaded sulfated sodium salt of β-cyclodextrin; the blue arrows indicate the characteristic absorption peaks of icariin. B, SEM image of sulfated sodium salt of β-cyclodextrin (I), icariin (II), and icariin-loaded sulfated sodium salt of β-cyclodextrin (III). C, SEM image of the luminal surface of decellularized small-caliber TEBVs (I), small-caliber TEBVs cross-linked with collagen (II), and TEBVs modified by icariin-loaded sulfated sodium salt of β-cyclodextrin; the red arrows indicate the icariin-loaded sulfated sodium salt of β-cyclodextrin (III). D, The activated partial thromboplastin time of blood of mouse added with PBS, icariin, sodium salt of β-cyclodextrin and icariin-loaded sulfated sodium salt of β-cyclodextrin. #, P>0.05; *, P<0.05.

  • Figure 4

    Icariin-loaded sulfated sodium salt of β-cyclodextrin modified TEBVs keep long patency. Dissection, H&E staining, Masson’s Trichrome staining and CTA results of control group (A), sulfated sodium salt of β-cyclodextrin modified TEBVs group (B), and icariin-loaded sulfated sodium salt of β-cyclodextrin-modified TEBVs group (C); the white arrows indicate the small-caliber TEBVs in vivo and the blue squareness indicate thrombosis in the small-caliber TEBVs after surgery.

  • Figure 5

    The endothelialization of Icariin-loaded sulfated sodium salt of β-cyclodextrin modified TEBVs. A, Endothelial cells in cryosections were immunostained for CD31 (red) in control TEBVs (a), sulfated sodium salt of β-cyclodextrin modified TEBVs (b), and icariin-loaded sulfated sodium salt of β-cyclodextrin modified TEBVs (c). B, SME showed that the growth of endothelial cells on the luminal surface of icariin-loaded sulfated sodium salt of β-cyclodextrin modified TEBVs; the red arrows indicate the endothelial cells.

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