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Enhanced vascularization in hybrid PCL/gelatin fibrous scaffolds with sustained release of VEGF.

Wang K, Chen X, Pan Y, Cui Y, Zhou X, Kong D, Zhao Q - Biomed Res Int (2015)

Bottom Line: In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days.In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells.More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.

ABSTRACT
Creating a long-lasting and functional vasculature represents one of the most fundamental challenges in tissue engineering. VEGF has been widely accepted as a potent angiogenic factor involved in the early stages of blood vessel formation. In this study, fibrous scaffolds that consist of PCL and gelatin fibers were fabricated. The gelatin fibers were further functionalized by heparin immobilization, which provides binding sites for VEGF and thus enables the sustained release of VEGF. In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days. In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells. More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF. Therefore, the heparinized PCL/gelatin scaffolds developed in this study may be a promising candidate for regeneration of complex tissues with sufficient vascularization.

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Related in: MedlinePlus

Representative hematoxylin and eosin (H&E) staining of explanted scaffolds after subcutaneous implantation for 2 (a, c, e, and g) and 4 (b, d, f, and h) weeks (n = 3): PCL (a and b); VEGF loaded PCL (c and d); VEGF loaded Hep-PCL/Gel-1 (e and f); VEGF loaded Hep-PCL/Gel-2 (g and h) (scale bars = 1 mm), and the corresponding quantitative analysis of cell migration (i). *P < 0.05; #P < 0.001.
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fig6: Representative hematoxylin and eosin (H&E) staining of explanted scaffolds after subcutaneous implantation for 2 (a, c, e, and g) and 4 (b, d, f, and h) weeks (n = 3): PCL (a and b); VEGF loaded PCL (c and d); VEGF loaded Hep-PCL/Gel-1 (e and f); VEGF loaded Hep-PCL/Gel-2 (g and h) (scale bars = 1 mm), and the corresponding quantitative analysis of cell migration (i). *P < 0.05; #P < 0.001.

Mentions: Angiogenesis in the VEGF loaded PCL/Gel scaffolds was evaluated by subcutaneous implantation in rats. After 4 weeks of implantation, the H&E images clearly show that the scaffold was almost fully cellularized (Figures 6(b), 6(d), 6(f), and 6(h)). As mentioned before, rapid and sufficient cellularization is the prerequisite for vascularization. Previous studies have shown that the relatively small pore size in electrospun scaffolds often limits the cell infiltration. In this study, the pore size was optimized by the method previously developed [14], making the scaffold favorable for cell infiltration and migration. The cell migration rates in all groups exceed 90% after 4 weeks (Figure 6(i)).


Enhanced vascularization in hybrid PCL/gelatin fibrous scaffolds with sustained release of VEGF.

Wang K, Chen X, Pan Y, Cui Y, Zhou X, Kong D, Zhao Q - Biomed Res Int (2015)

Representative hematoxylin and eosin (H&E) staining of explanted scaffolds after subcutaneous implantation for 2 (a, c, e, and g) and 4 (b, d, f, and h) weeks (n = 3): PCL (a and b); VEGF loaded PCL (c and d); VEGF loaded Hep-PCL/Gel-1 (e and f); VEGF loaded Hep-PCL/Gel-2 (g and h) (scale bars = 1 mm), and the corresponding quantitative analysis of cell migration (i). *P < 0.05; #P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390103&req=5

fig6: Representative hematoxylin and eosin (H&E) staining of explanted scaffolds after subcutaneous implantation for 2 (a, c, e, and g) and 4 (b, d, f, and h) weeks (n = 3): PCL (a and b); VEGF loaded PCL (c and d); VEGF loaded Hep-PCL/Gel-1 (e and f); VEGF loaded Hep-PCL/Gel-2 (g and h) (scale bars = 1 mm), and the corresponding quantitative analysis of cell migration (i). *P < 0.05; #P < 0.001.
Mentions: Angiogenesis in the VEGF loaded PCL/Gel scaffolds was evaluated by subcutaneous implantation in rats. After 4 weeks of implantation, the H&E images clearly show that the scaffold was almost fully cellularized (Figures 6(b), 6(d), 6(f), and 6(h)). As mentioned before, rapid and sufficient cellularization is the prerequisite for vascularization. Previous studies have shown that the relatively small pore size in electrospun scaffolds often limits the cell infiltration. In this study, the pore size was optimized by the method previously developed [14], making the scaffold favorable for cell infiltration and migration. The cell migration rates in all groups exceed 90% after 4 weeks (Figure 6(i)).

Bottom Line: In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days.In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells.More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.

ABSTRACT
Creating a long-lasting and functional vasculature represents one of the most fundamental challenges in tissue engineering. VEGF has been widely accepted as a potent angiogenic factor involved in the early stages of blood vessel formation. In this study, fibrous scaffolds that consist of PCL and gelatin fibers were fabricated. The gelatin fibers were further functionalized by heparin immobilization, which provides binding sites for VEGF and thus enables the sustained release of VEGF. In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days. In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells. More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF. Therefore, the heparinized PCL/gelatin scaffolds developed in this study may be a promising candidate for regeneration of complex tissues with sufficient vascularization.

Show MeSH
Related in: MedlinePlus