Is it Possible to Create Readily Available Tissue-Engineered Vascular Grafts Without Using Cells?

Abstract

Introduction - In modern vascular surgery remains the problem of small-diameter vascular grafts. Autologous or synthetic vascular grafts are used routinely for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering. Currently, there are a number of techniques to receipt such artificial vessel, some of which are already in clinical trials. The method of using acellular biodegradable scaffold suggests that host cells can regenerate new vascular wall in situ, thats allows to overcome the scalability issue and make the grafts available off-the-shelf. The aim of the study is a comprehensive assessment of bioresorbable prosthesis from L-polylactide (PLA), and determining the possibility of its use as acellular vascular graft available off-the-shelf. Methods - Tubular grafts were obtained by the electrospinning method, (1.2 mm inner diameter) on the basis of nonwoven nano- and microfiber biodegradable polymer PLA. Mechanical characteristics such as tensile strength ,Young’s modulus E, and tensile deformation at break ofthe samples were determined using a UTS 10 universaltesting machine (Germany). Porosity parameters were determined by mercury porosimetry and BET method. Cytology analyses were performed with nanofibersfrom PLA and culture of mesenchymal stem cellsobtained from adipose tissue (ASCs). To assess the degree of cell adhesion toPLA grafts investigated materials were placed insquare-hole board (Nunc, USA). Investigation of barrier propertiesof tubular grafts were carried out on a developed laboratory setup. Obtained grafts were implanted in the abdominal aorta of rats (n=18). Follow-up was 16 months. The material was subjected to histological examination, electron microscopy, immunohistochemistry CD 31 +. After 14 months implantation angiography was performed (n=1). Results - During the operations and by the results of the investigation physical and mechanical properties it has been shown that obtained grafts are suitable for sewing in the bloodstream. For grafts from L-polylactide the pore volume was 78% and the surface area per gram of polymer 3.6 m2 (S BET).Investigation of adhesion and proliferation of mesenchymal stem cells derived from adipose tissue of rats showed safety and biocompatibility of used materials. All grafts formed neointima, with no signs of hyperplasia in the areas of anastomoses. Patency for PLA grafts 88% (n = 18). After 16 months (n=3) histology shows total resorption of PLA fibers, new vascular wall consist of connecctive tissue with endotelial lining, but all zone of reconstruction was presented by aneurysm. Conclusion - Small diameter vascular prostheses with high porosity obtained by electrospinning from PLA have sufficient exploitation mechanical properties. In in vivo experiments proved its safety, biocompatibility. Received patency rates are satisfactory for grafts with small diameter. Low mechanical properties of the connective tissue formed in the area of reconstruction have led to the formation of aneurysms. To sum up, the need for the introduction of cells in the wall of the graft in vitro before implantation is not in doubt.