Development of small-diameter vascular grafts using PCL/PLA/gelatin/PVA/hyaluronic acid nanofibers containing VEGF/enoxaparin
The extending demands for narrow-diameter vascular grafts to restore damaged arteries have captivated researcher's attention. The absence of appropriate vascular substitutes is due to the poor patency rate of small-caliber synthetic grafts caused by thrombosis and vessel hemodynamic mismatch th...
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| Veröffentlicht in: | Journal of drug delivery science and technology Jg. 101; S. 106171 |
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| Hauptverfasser: | , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
Elsevier B.V
01.11.2024
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| ISSN: | 1773-2247 |
| Online-Zugang: | Volltext |
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| Zusammenfassung: | The extending demands for narrow-diameter vascular grafts to restore damaged arteries have captivated researcher's attention. The absence of appropriate vascular substitutes is due to the poor patency rate of small-caliber synthetic grafts caused by thrombosis and vessel hemodynamic mismatch that induce intimal hyperplasia. We developed small-diameter vascular grafts in two layers through electrospinning. The inner layer was fabricated by gelatin/polyvinyl alcohol (PVA)/hyaluronic acid/enoxaparin and vascular endothelial growth factor (VEGFs) and the outer layer was manufactured via polycaprolactone (PCL)/polylactic acid (PLA)/hyaluronic acid. The products were characterized by atomic force microscope (AFM), scanning electron microscope (SEM), water contact angle (WCA), attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), swelling test, mechanical test, and release rate. Blood compatibility tests including blood clotting time, hemolysis, and human platelet sedimentation were measured. The interactions of human umbilical vein endothelial cells (HUVECs) and human endometrial stem cells (hEnSCs) with nanofibrous vascular grafts were detected by SEM, viability assay, and DAPI staining. The results exhibited the produced small-diameter vascular grafts had proper antithrombotic properties due to two factors of VEGF and enoxaparin. After two months of the subcutaneous implantation of the scaffolds on the back of rats, the tubular vascular grafts lacked any macroscopic and histological signs of acute inflammation and had appropriate degradation rates. Furthermore, lumen patency was observed after 2 months. Consequently, VEGF and enoxaparin improves cell and blood compatibility in the small-diameter vascular grafts.
Schematic representation of VEGF/Enoxaparin-loaded small diameter vascular grafts. A) Fabrication of vascular grafts by electrospinning in two layers using gelatin, poly vinyl alcohol (PVA), hyaluronic acid (HA), vascular endothelial growth factor (VEGF), and enoxaparin (En) as an inner layer and polycaprolactone (PCL), polylactic acid (PLA) and hyaluronic acid as an outer layer; B) In vitro characterization tests and C) Subcutaneous implantation of vascular grafts and In vivo characterization tests. [Display omitted] |
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| ISSN: | 1773-2247 |
| DOI: | 10.1016/j.jddst.2024.106171 |