Abstract
Tissue-engineered vascular graft for the reconstruction of small arteries is still an unmet clinical need, despite the fact that a number of promising prototypes have entered preclinical development. Here we test Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)Poly(ε-caprolactone) 4-mm-diameter vascular grafts equipped with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and stromal cell-derived factor 1α (SDF-1α) and surface coated with heparin and iloprost (PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo, n = 8) in a sheep carotid artery interposition model, using biostable vascular prostheses of expanded poly(tetrafluoroethylene) (ePTFE, n = 5) as a control. Primary patency of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts was 62.5% (5/8) at 24 h postimplantation and 50% (4/8) at 18 months postimplantation, while all (5/5) ePTFE conduits were occluded within the 24 h after the surgery. At 18 months postimplantation, PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts were completely resorbed and replaced by the vascular tissue. Regenerated arteries displayed a hierarchical three-layer structure similar to the native blood vessels, being fully endothelialised, highly vascularised and populated by vascular smooth muscle cells and macrophages. The most (4/5, 80%) of the regenerated arteries were free of calcifications but suffered from the aneurysmatic dilation. Therefore, biodegradable PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts showed better short- and long-term results than bio-stable ePTFE analogues, although these scaffolds must be reinforced for the efficient prevention of aneurysms.
Highlights
Despite immense efforts to reduce morbidity from atherosclerotic vascular disease [1] which have resulted in a steady decrease in the number of coronary artery bypass grafting procedures worldwide, this treatment modality remains common (82 procedures per 100,000 US adults annually) [2,3]
We found that PHBV/PCL[vascular endothelial growth factor (VEGF)-basic fibroblast growth factor (bFGF)-SDF]Hep/Ilo grafts demonstrated promising primary patency rate (62.5% and 50% at 24 h and 18 months postimplantation) in contrast to ePTFE conduits all of which were occluded within 24 h after the surgery
We first conducted a tensile testing of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts to reveal whether the Hep/Ilo attachment affects their mechanical properties
Summary
Despite immense efforts to reduce morbidity from atherosclerotic vascular disease [1] which have resulted in a steady decrease in the number of coronary artery bypass grafting procedures worldwide, this treatment modality remains common (82 procedures per 100,000 US adults annually) [2,3]. Vascular bypass implies the use of autologous blood vessel conduits (e.g., saphenous vein or internal mammary artery (IMA)) [4,5] while other types of arterial reconstruction involve biostable tubular scaffolds (e.g., Poly(ethylene terephthalate) (PET), expanded poly(tetrafluoroethylene) (ePTFE), or polyurethane prostheses) [6,7]. The limited availability of autografts (because of prior surgery, extensive atherosclerosis, or anatomical incompatibility) and high rate of thrombotic occlusion and neointimal hyperplasia in small diameter biostable prostheses limit their use in cardiovascular surgery [8,9]. Current additive manufacturing technologies permit layer-by-layer incorporation of bioactive factors (e.g., growth factors or chemokines) to the tubular scaffold and their controlled release to guide endothelial/vascular smooth muscle specification and vascular tissue regeneration [11]. Propagation of contractile and synthetic mesenchymal cells (which can have smooth muscle or fibroblast identity), and production of the extracellular matrix (ECM) are key factors underlying high long-term primary patency of TEVGs [11,12,13]
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