bFGF and SDF-1α Improve In Vivo Performance of VEGF-Incorporating Small-Diameter Vascular Grafts

Abstract

Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can induce tumor-like vasculature; thereby, other bioactive factors are needed to support VEGF-driven endothelialization and successful recruitment of smooth muscle cells. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer with the following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model. The latter graft prototype showed higher primary patency rate. We found that the two-layer structure improved surface topography and mechanical properties of the grafts. Further, the combination of bFGF, SDF-1α, and VEGF improved endothelialization compared with VEGF alone, while bFGF induced a rapid formation of a smooth muscle cell layer. Taken together, these findings show that the two-layer structure and incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF provide a higher primary patency and therefore improved in vivo performance.

Tissue-Engineered Carotid Artery Interposition Grafts Demonstrate High Primary Patency and Promote Vascular Tissue Regeneration in the Ovine Model

“…The reason behind this was the unexpectedly [35,36] rapid resorption of the PHBV/PCL scaffold, which lost its integrity 6 months postimplantation and was almost completely resorbed 18 months postimplantation. In rats, all grafts were intact 12 months postimplantation and did not display any signs of aneurysm formation [27,32]. Intriguingly, these results fully correspond to a recent paper which also reported a striking difference in the degradation rates of TEVGs between small and large animal models [44].…”

“…Biodegradable TEVGs (4 mm diameter, ≈400 µm thickness and 4 cm length) were fabricated using emulsion electrospinning (Nanon-01A, MECC, Tokyo, Japan) from PHBV (403105, Sigma-Aldrich, Saint Louis, MO, USA): PCL (440744, Sigma-Aldrich, Saint Louis, MO, USA) (5:10%)/chloroform (366927, Sigma-Aldrich, Saint Louis, MO, USA) solution using the following parameters: 23 kV voltage, 0.5 mL/h feed rate, 2 mm rotating drum diameter, 22G needle, and 150 mm tip-to-collector distance. Abovementioned polymer ratio was determined in our previous studies [25,31,32]. In all these investigations, PHBV/PCL vascular grafts did not show any signs of dissolution as long as 1 year after implantation into rat abdominal aorta.…”

“…The applied electrospinning technique generated nanoscale polymer fibres which formed interconnected microsized pores, thereby increasing the area for cell-ECM interactions [11,43]. Combined with bioactive factors, such construction of the conduit potentiated migration, attachment, and guided differentiation of blood-derived cells, consequently improving the integration of the implant with the host tissues [32]. However, preliminary studies found unacceptably high frequency of thrombosis when this prototype was applied to replace ovine carotid artery.…”

Controlled and Synchronised Vascular Regeneration upon the Implantation of Iloprost- and Cationic Amphiphilic Drugs-Conjugated Tissue-Engineered Vascular Grafts into the Ovine Carotid Artery: A Proteomics-Empowered Study

“…Further, TEVGs did not demonstrate any signs of the infection such as precipitation of complement components or neutrophil markers, instead showing informative signatures of chronic inflammation remodeling, namely structural lysosomal proteins (which are well-established macrophage markers) and cathepsins, known as lysosomal but not blood- or extracellular matrix-derived enzymes [ 62 , 63 , 64 ]. This type of remodeling has already been reported in several studies [ 19 , 65 , 66 , 67 , 68 ], as well as the rapid degradation of the polymer scaffolds in sheep as compared to rats [ 25 , 34 , 69 , 70 , 71 , 72 , 73 ]. As synchronisation of polymer biodegradation and vascular regeneration evidently occurs 6 months postimplantation (the duration of follow-up in our study), and PCL is almost completely degraded and replaced with de novo vascular tissue, it seems unlikely that the TEVG will become considerably closer to the native carotid artery in the long term.…”

Phytochemical Constituents and Ameliorative Effect of the Essential Oil from Annona muricata L. Leaves in a Murine Model of Breast Cancer

“…Serum VEGF was determined with a rat VEGF ELISA kit (Sigma Chemical Co., Hamburg, Germany) [ 35 ]. The procedure was carried out following the Sigma protocol.…”