Biodegradable Vascular Graft Reinforced With a Biodegradable Sheath

Abstract

Background. Tissue-engineered vascular grafts can be reinforced by a biostable or biodegradable polymer sheath. A combination of electrospinning, routinely used for fabrication of biodegradable tubular grafts, and the layer-by-layer coating allows forming a polymeric sheath ensuring long-term integrity and high biocompatibility of the vascular grafts after the implantation. Aim To evaluate mechanical properties and in vivo performance of biodegradable small-diameter vascular grafts with a reinforcing sheath.Methods. Tubular grafts (4 mm diameter) were fabricated from poly(3-hydroxybutyrate-co3-hydroxyvalerate) and poly(ε-caprolactone) by emulsion electrospinning with the incorporation of vascular endothelial growth factor (VEGF) into the inner third of the graft and basic fibroblast growth factor (bFGF) along with stromal cell-derived factor-1α (SDF-1α) into the outer two thirds of the graft wall. Poly(ε-caprolactone) sheath was formed by the layer-by-layer coating. Upon graft fabrication, scanning electron microscopy was performed to assess the grafts’ surface, tensile testing allowed evaluating mechanical properties. The samples were implanted into the ovine carotid artery (n = 5 animals) for 12 months with the subsequent histological examination.Results. Sintering temperature of 160°C during the extrusion allowed effective and delicate merging of poly(ε-caprolactone) coating with the outer surface of the poly(3hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) tubular graft. The thickness of poly(ε-caprolactone) fiber was 380–400 μm, the increment of the reinforcing filament was 1 mm. The reinforcing sheath led to a 3-fold increase in durability and elastic modulus of the vascular grafts. At the 12-months follow-up, the grafts reported retained integrity. No signs of inflammation or calcification were found.Conclusion. The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(ε-caprolactone) vascular grafts with hierarchically incorporated growth factors and the reinforced poly(ε-caprolactone) spiral sheath demonstrated improved mechanical properties while retaining integrity and high biocompatibility after the long-term implantation into the 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

“…The absence of elastic fibers is a considerable and general disadvantage of biodegradable TEVGs, albeit a recent study reported the successful formation of the internal elastic lamina by the embedding of tropoelastin fibers into the poly(glycerol sebacate), a highly elastic and degradable biomaterial, during electrospinning [ 74 ]. Yet, the enclosure of poly(glycerol sebacate) or fibrin scaffold into the PCL [ 75 , 76 ] or poly(glycolic acid) [ 77 ] sheath efficiently prevented the development of aneurysms, similar to our previous work [ 60 ]. The lack of contractile VSMCs under significant cyclic strain characteristic of the ovine carotid artery was unexpected, as this is a major stimulus of such molecular specification [ 78 , 79 , 80 ].…”

“…Previously, our group reported an efficient approach for increasing haemocompatibility and thrombosis prevention by immobilising an anticoagulant heparin and a vasodilator/antiplatelet drug, iloprost, to the luminal surface of PCL-based TEVGs [ 25 ]. Further, we have developed an anti-aneurysmatic PCL sheath attached to the TEVG outer surface by fused deposition modeling, a method employing 3D printing extrusion [ 60 ]. Here, we combined iloprost and a cationic amphiphilic drug (CAD) 1,5-bis-(4-tetradecyl-1,4-diazoniabicyclo [2.2.2] octan-1-yl) pentane tetrabromide, which has higher antibacterial and antiviral properties in comparison with other CADs because of RNAse activity.…”