scholarly journals Results of long-term patency of small-diameter biodegradable vascular prostheses with atrombogenic drug coating of sheep model

2021 ◽  
Vol 10 (2) ◽  
pp. 36-39
Author(s):  
E. O. Krivkina ◽  
L. V. Antonova
Keyword(s):  
Growth Factor ◽  
Vascular Tissue ◽  
Small Diameter ◽  
Layer By Layer ◽  
Sheep Model ◽  
Vascular Prostheses ◽  
Polymer Framework ◽  
Endothelial Growth Factor ◽  
Drug Coating

Background. Preclinical tests of biodegradable small diameter vascular prostheses on a sheep model have been carried out.Aim. To assess the results of long-term patency and remodeling of biodegradable vascular prostheses based on polyhydroxybutyrate / valerate and polycaprolactone with an atrombogenic drug coating in a large laboratory animal model.Methods. We researched vascular prostheses made of polyhydroxybutyrate / valerate and polycaprolactone (PHBV/PCL) 4 mm in diameter with layer-by-layer vascular endothelial growth factor incorporated into the polymer framework, the main fibroblast growth factor, chemoattractant molecule containing SDF-1a (GFmix) surface, and additional modifying drug surface heparin and iloprost (PHBV/PCL/ GFmix/Heparin/Iloprost). Animals with implanted synthetic Gore-Tex vascular grafts with a diameter of 4 mm were included into a comparison group.Results. After one day of implantation it was revealed that the patency of biodegradable PHBV/PCL/GFmix/Heparin/Iloprost prostheses was 62.5%, while synthetic Gore-Tex prostheses were thrombosed in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable vascular PHBV/PCL/ GFmix/Heparin/Iloprost prostheses decreased to 50%. Passable drug-eluting polymer grafts were completely resorbed after 18 months of implantation, and aneurysmically expanded newly formed vascular tissue was formed in their place.Conclusion. Vascular prostheses made of polyhydroxybutyrate/valerate and polycaprolactone showed better long-term patency results than synthetic prostheses used in the clinical practice. However, the strengthening of the external framework of the prostheses is required in order to prevent the formation of aneurysms. 

scholarly journals BIODEGRADABLE VASCULAR GRAFT REINFORCED WITH A BIODEGRADABLE SHEATH

2019 ◽  
Vol 8 (2) ◽  
pp. 87-97
Author(s):  
L. V. Antonova ◽  
E. O. Krivkina ◽  
M. A. Rezvova ◽  
V. V. Sevost'yanova ◽  
A. V. Mironov ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Growth Factor ◽  
Carotid Artery ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Fold Increase ◽  
Layer By Layer ◽  
Layer Coating

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.

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

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2637
Author(s):  
Larisa V. Antonova ◽  
Evgenia O. Krivkina ◽  
Viktoriia V. Sevostianova ◽  
Andrey V. Mironov ◽  
Maria A. Rezvova ◽  
...  
Keyword(s):  
Growth Factor ◽  
Carotid Artery ◽  
Vascular Tissue ◽  
Layer Structure ◽  
Primary Patency ◽  
Long Term Results ◽  
Preclinical Development ◽  
Vascular Prostheses ◽  
Stromal Cell Derived Factor ◽  
Endothelial Growth Factor

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.

scholarly journals Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab

2014 ◽  
Vol 48 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Robert Königsberg ◽  
Julia Maierhofer ◽  
Tanja Steininger ◽  
Gabriele Kienzer ◽  
Christian Dittrich
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Growth Factor ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Over Expression ◽  
Single Target ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

AbstractBackground. The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF.Case report. The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented. Our patient has been receiving the combined double administration of bevacizumab and trastuzumab for more than 4 years.Conclusions. This case report shows that (a) the combined double administration of bevacizumab and trastuzumab was be clinically effective. (b) The combination of bevacizumab and trastuzumab is safe and non-toxic. (c) Bevacizumab and trastuzumab can be used as a long-term application

scholarly journals Transient Exposure of Endothelial Cells to Doxorubicin Leads to Long-Lasting Vascular Endothelial Growth Factor Receptor 2 Downregulation

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 210
Author(s):  
Silvia Graziani ◽  
Luca Scorrano ◽  
Giovanna Pontarin
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Drug Withdrawal ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
P53 Expression ◽  
Endothelial Growth Factor

Doxorubicin (Dox) is an effective antineoplastic drug with serious cardiotoxic side effects that persist after drug withdrawal and can lead to heart failure. Dysregulation of vascular endothelium has been linked to the development of Dox-induced cardiotoxicity, but it is unclear whether and how transient exposure to Dox leads to long-term downregulation of Endothelial Vascular Endothelial Growth Factor Receptor type2 (VEGFR2), essential for endothelial cells function. Using an in vitro model devised to study the long-lasting effects of brief endothelial cells exposure to Dox, we show that Dox leads to sustained protein synthesis inhibition and VEGFR2 downregulation. Transient Dox treatment led to the development of long-term senescence associated with a reduction in VEGFR2 levels that persisted days after drug withdrawal. By analyzing VEGFR2 turnover, we ruled out that its downregulation was depended on Dox-induced autophagy. Conversely, Dox induced p53 expression, reduced mTOR-dependent translation, and inhibited global protein synthesis. Our data contribute to a mechanistic basis to the permanent damage caused to endothelial cells by short-term Dox treatment.

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