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    SOSTITUTI BIOLOGICI VASCOLARI A BASE DI ACIDO IALURONICO

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    The discovery of an adequate tissue substitute for the regeneration of small vessels has become one of the most debated issues in the last years. This is due to recent advances in regenerative medicine, which offers new cellular types and biomaterials, and the large clinical applications that this product may have, ranging from the replacement of the coronary vessels to correction of peripheral vascular malformations in pediatric patients. The biomaterials used so far for large caliber vascular prostheses have yielded disappointing results when applied in vessels with a smaller diameter than 6 mm, leading to occlusion of the vessel lumen in short periods. The finding of an ideal product in this area is difficult to reach first of all for the cellular complexity of the vascular tissue but also for involvedness of cellular interactions (vascular cells - red blood cells), mechanical properties and convolution of experimental models in vivo and in vitro. The aim of this observational study was to test a biomaterial based on hyaluronic acid in three different experimental models and to develop a model of tissue healing, to prove venous regeneration and functionality of this construct in similar to daily clinical practice conditions. The study is constituted of 3 different projects on animal models. In the first project patches of hyaluronic acid have been used to repair defects on the vascular wall of abdominal aorta of rat, there were operated 20 animals ( 250-350 g ). After isolation of the abdominal aorta, a breach was opened in it (1 x 5 mm) and the defect was repaired by placing the patch of hyaluronic acid. Tissue samples were evaluated after their removal to 1, 2, 4, 8 and 16 weeks with histological and immunohistochemical studies. In the second project a tubular conduit of hyaluronic acid ( 2 mm diameter, 1.5 cm length ) was placed after interruption of cava vein of the rat as a resorbable guide to vein regeneration . The tissue samples were evaluated after 30, 90 and 60 days with histological and immunohistochemical methods. In the third project the conduits of hyaluronic acid have been placed in vessels forming the vascular pedicle of a free tissue flap (groin flap) in the rabbit. 16 animals were operated, 8 of them were a control group, where microanastomosis were executed without interposition of any conduit. The vitality of the flaps was evaluated after 1, 2 and 3 weeks postoperatively. In the first project was detected a progressive regeneration of the arterial vessel in all its components, starting from the intima and adventitia and continuing with the muscularis. After 16 weeks, the biomaterial was completely degraded and replaced by a new vascular wall composed of endothelial cells, smooth muscle cells, collagen and elastin arranged in layers. In the project with the installation of venous ducts was documented a progressive venous regeneration already complete after 30 days of implantation but consolidated in 60 days. The total degradation after 4 months proved a protected environment for the regeneration during the initial stages . In the last project all flaps were viable after 3 weeks in cases of replacement and in control group , ¾ of them were vital in the case of venous replacement. There were recorded some complications such as dehiscence of the surgical wound and the seromas formation, which however did not appear to be related to implanted prosthesis but to surgical procedures and the specific animal. After these observations is claimable that the hyaluronic acid patch is able to support vascular regeneration. From this experiment was extrapolated a three-dimensional model of vascular tissue healing with the various stages. With the use of the tubular duct into the cavavein was obtained regeneration without the occlusion up to 4 months after implantation. Finally, tubular conduits successfully supported the vascularization of a free flap, and in this way was proved the functionality of the vascular component. These results open new perspectives in vascular , pediatric and cardiac surgery. Specifically in reconstructive surgery, these products could be used for the elongation of vascular pedicles in transplantation free flaps surgery or replants

    Alternative conduits for microvascular anastomoses

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    Thrombotic events in vascular substitutes are the main cause of obliteration of most microvascular prostheses and subsequent failure of microvascular anastomoses. The development of new biomaterials for vascular replacement aims to obtain an ideal graft for microvascular surgery. Completely bioresorbable vascular prostheses with the capacity to induce regeneration and growth of a new vascular segment seem to overcome the limitations of contemporary artificial prostheses, mostly made of artificial materials and lacking the capacity to grow and be remodeled. Autologous vessels are currently the most used material for small-diameter arterial replacement. Immune acceptance is a major advantage offered by this technique, but the time required is a limitation in emergency surgery. The need for a prosthetic graft that would have the same properties as a small-diameter conduit has led investigators to pursue many avenues in vascular biology. This article details the development of microvascular synthetic prostheses, clarifying the current status and the future aims

    Alternative Conduits for Microvascular Anastomoses.

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    Thrombotic events in vascular substitutes are the main cause of obliteration of most microvascular prostheses and subsequent failure of microvascular anastomoses. The development of new biomaterials for vascular replacement aims to obtain an ideal graft for microvascular surgery. Completely bioresorbable vascular prostheses with the capacity to induce regeneration and growth of a new vascular segment seem to overcome the limitations of contemporary artificial prostheses, mostly made of artificial materials and lacking the capacity to grow and be remodeled. Autologous vessels are currently the most used material for small-diameter arterial replacement. Immune acceptance is a major advantage offered by this technique, but the time required is a limitation in emergency surgery. The need for a prosthetic graft that would have the same properties as a small-diameter conduit has led investigators to pursue many avenues in vascular biology. This article details the development of microvascular synthetic prostheses, clarifying the current status and the future aim

    In vivo regeneration of small-diameter (2mm) arteries and veins using a polymer scaffold

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    The difficulty of obtaining significant long-term patency and good wall mechanical strength in vivo has been a significant obstacle in achieving small-diameter vascular prostheses. The aim of the present study was to develop a prosthetic graft that could perform as a small-diameter vascular conduit for artery and vein regeneration. 60 Male Wistar rats weighing 250-350 g were used. Tubular structures of hyaluronan (HYAFF-11 tubules, 2 mm diameter, 1 cm length) were grafted in the abdominal aorta (nZ30), and in the vena cava (nZ30) of rats as temporary absorbable guides to promote regeneration of vascular structures. No anticoagulants were used either before or after the operation. Performance was assessed at 5, 15, 30, 60, 120, and 180 days after surgery by histology (haematoxylin-eosin and Weighert solution), immunohistochemistry (antibodies to von Willebrand factor, CD34, vascular endothelial growth factor receptor-2 and to Myosin Light Chain Kinase), and ultra-structural analysis. These experiments resulted in three novel findings: 1) complete endothelialization of the tube’s luminal surface occurred; 2) sequential regeneration of vascular components led to complete vascular wall regeneration 15 days after surgery; and 3) the biomaterial used created the ideal environment for the delicate regeneration process during the critical initial phases, yet its biodegradability allowed for complete degradation of the construct four months after implantation, at which time, a new artery and a new vein remained to connect the vascular stumps. This study assesses the feasibility to create a completely biodegradable vascular regeneration guide in vivo for artery and vein regeneration. The most important novel finding is represented by the ability of proposed vascular prostheses to sequentially orchestrate vascular regeneration events needed for very small artery and vein reconstruction that up to now, given the great difficulty to obtain their in vivo significant long term patency and good wall mechanical strength, is defined as the holy grail of vascular biology. Moreover, this research opens new strategies in the prefabrication of free flaps, allowing the complete in vivo regeneration of a vascular pedicle (artery and vein)
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