However, a specific class of SFF methods is currently suited for direct processing of nanobiomaterials (Fig. Piccone V. Alternative techniques in coronary artery reconstruction. Improved reactivity, bioactivity, electrical and optical properties, strength and magnetic characteristics are of particular interest to the biomedical field (Ferrari, 2005; Qin et al., 1999; Vasir et al., 2005). In order to mimic the physiological environment of the artery, including its mechanical nature, bioreactors are often employed. Foremost, in the acute phase following implantation, the scaffold must fulfill the key mechanical functions of the tissue that is being replaced. While the use of bioreactors can provide a more physiological environment for culturing and studying tissue-engineered blood vessels, it may not be necessary. Increased blood flow results in an increase in the inner diameter of the blood vessel. Research will continue in these areas as many adult stem cells are immunoprotected and can provide necessary function, possibly eliminating the need for allogeneic cell sources. Transmural pressure produces hoop stress in the vessel wall. In another study, Anghel et al. The presence of EPCs promoted more tubular structures per mm2 and greater EC marker-expressing tubular structures [112]. PEUU, Poly(ester urethane) urea; PGA, poly(glycolic acid); PGS, poly(glycerol sebacate). Ann Vasc Surg. In this review, the progress to date and the barriers remaining are addressed. Because the foremost role of the scaffold following implantation is to temporarily fulfill the key mechanical functions of the replaced tissue, it is also essential to consider the physiological loading state of the native tissue and tissue remodeling of scaffolds from human recipient. The development of antibacterial, anti-inflammatory, and tissue-regenerative surface modifications constitutes a major challenge to guarantee implant achievement. The ideal strain profiles are still being determined; strain amplitude and rate influences the mechanical properties of the engineered tissue, and recent studies show that a more complex profile incrementally increasing strain rate may yield better results (Syedain et al., 2008). PHAs have been widely used in the cardiovascular engineering for artery augmentation, cardiologic stents, vascular grafts, heart valves and pericardial patches [20]. Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. In another study of heart valve TE using PGA meshes, computational modeling based on mechanically induced tissue remodeling predicted leaflet compression and subsequent shortening as a result of physiological loading pressures [55]. Processes such as stereolithography (SL), nanocomposite deposition system (NCDS), selective laser sintering (SLS), inkjet printing, aerosol jet printing and extrusion-based systems are among the most widely used SFF approaches for nanobiomaterials processing. B) Quantification of the percentage of cells positive for oil red O (upper image) and a quantitative assay for alkaline phosphatase activity (lower image) showing MSCs increased osteogenic differentiation in gels with faster stress relaxation (reproduced from Chaudhuri, Gu et al. In the body, the cellular microenvironment comprises a variety of nanostructured surfaces (Flemming et al., 1999; Elias et al., 2002; Sniadecki et al., 2006; Lim and Donahue, 2007; Chung et al., 2007). 2010 Jan;5(1):107-20. doi: 10.2217/rme.09.77. Expanding smooth muscle cells in vitro is common practice, but can result in a modulation to a more synthetic smooth muscle cell phenotype where cells lose much of their contractile apparatus. Areas of disturbed or stagnant flow are prone to forming atherosclerotic plaques, and such atherosclerosis is a highly localized disease. In the tissue engineering of a blood vessel substitute there are a number of critical issues that are being addressed by a wide variety of investigators. VSMCs benefited from coculture with monocytes on both film and porous scaffold forms of D-PHI [67,106,107]. It is notable that the human pericyte-seeded scaffolds showed 100% patency without dilation [41]. Making blood vessel networks is tricky business because the system doesn’t always behave how investigators expect. (2012) revealed that nanocoating could prevent wound microbial contamination and subsequent biofilm development on viable tissues or implanted devices. Kristofik is working to create better small-diameter (less than 6mm) arterial grafts. See this image and copyright information in PMC. Coronary bypass procedures or autologous grafts are usually considered in case of small diameter grafts. An additional positive feature of the P(4HB) patching material was a self-sealing property preventing blood leakage compared with a polytetrafluoroethylene (PTFE) patch, which leaves a hole for blood to leak [136]. [111]). Biodegradable polyurethane has been processed into tubular scaffolds by electrospinning, which was applied for blood vessel regeneration, because it has robust mechanical properties with good elasticity and biocompatibility. 1990;4:98–103. There are several approaches that will be discussed in the next section that avoid the use of bioreactors in order to minimize the culture time and try to achieve off-the-shelf availability. Kirklin JW, Barratt-Boyes BG. TE blood vessels based on relatively strong nonwoven poly(glycolic acid) (PGA) scaffolds exhibited burst pressures exceeding physiological requirements upon implantation (> 2000mmHg) [32]. The blood vessels are the part of the circulatory system that transports blood throughout the human body. Both cellularized scaffolds showed markedly improved patency after 8 weeks of implantation compared to the acellular scaffolds [40,41]. Kohli N, Sawadkar P, Ho S, Sharma V, Snow M, Powell S, Woodruff MA, Hook L, García-Gareta E. J Tissue Eng. The implanted engineered valve was properly functional with mobile leaflets without any stenosis, thrombus or aneurysm. Cleary MA, Geiger E, Grady C, Best C, Naito Y, Breuer C. Trends Mol Med. cocultured human hepatocytes with human umbilical vein ECs (HUVECs) on a polyetheretherketone PU membrane to promote vascularization of an in vitro engineered liver tissue [102]. A biodegradable poly(ester urethane)urea (PEUU) was blended with a phospholipid polymer of poly(methacryloyloxyethyl phosphorylcholine-co-methacryloyloxyethyl butyl urethane) (PMBU) (molar ratio = 70/30), in HFIP solvent, and then coelectrospun into a small diameter conduit (inner diameter, i.d. Hence, prior to the use of polyurethane scaffolds for blood vessel replacement, their hemocompatibility must be improved. The sections are stained with Masson’s trichrome which stains collagen blue, nuclei purple, and cytoplasm and muscle fiber red. Regen Med. The DPA-loaded scaffold showed improved blood compatibility in terms of lower red cell hemolysis and platelet deposition compared to the scaffold without DPA. After 8 weeks of implantation into a rat aorta model (end to end implantation), the phospholipid polymer-coated PEUU conduit had a higher patency of 92% than that of PEUU conduit alone (40%). The multiple layers of smooth muscle cells and a monolayer of endothelial cells were detected on the lumen. The additive nature of SFF technologies ensures minimal waste of scarce and expensive nanobiomaterials. Broad ranges of processing technologies have been developed with different applications and capabilities as their fundamentals are very diverse. Based on this model, the scaffold will be fabricated. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient's conditions. In another study, blends of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(propylene carbonate) (PPC) were prepared at various weight ratios for obtaining materials with properties more suitable for, Electrospun fibrous polyurethane scaffolds in tissue engineering, Adult progenitor cells or adult stem cells, Autologous cells or immunoprotected cells. Without a vascular network, cell death will occur in tissues greater than 1–2 cm thick, and some experiments and the structure of natural aorta suggest that a tissue thicker than approximately 0.2 cm requires an intrinsic vasculature (called the vasa vasorum). Rat cerebral endothelial cells (RCECs) were used to assess the cytocompatibility of PCL/PHBV, PCL, PHBV mats, respectively, and, also the tubular scaffolds made by electrospinning technique. Ventricular Septal Defect and Pulmonary Stenosis or Atresia. Effects of hemodynamics on blood vessel. Vascular grafting is used to repair or replace malfunctioning blood vessels in the arterial or venous systems due to damage or disease, like atherosclerosis and traumatic injury. Clipboard, Search History, and several other advanced features are temporarily unavailable. P(4HB) has been used with good success as a scaffold for preparing autologous cardiovascular tissue. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with … They had succeeded in developing a PHA based porous scaffolding material in the form of a trileaflet heart valve from a PGA nonwoven mesh solvent coated with P(4HB). The generated conduits have compliances comparable to those of the human artery. Interestingly, the leaflets replaced with porous and relatively more flexible P(3HHx-co-3HO)–PGA mesh were found to be more suitable in the in vivo study using lamb models. SFF is a fabrication technique used for building three dimensional (3D) parts layer-by-layer directly from computer-aided design (CAD) data in a short time. One of the most astonishing results of PHA based tissue engineering described to date was from Hoerstrup et al. It has been observed that human cells tend to attach, grow and proliferate on fibres with diameters smaller than those of cells (Teixeira et al., 2003). The synthetic polyesters at times are too stiff to function as flexible leaflets inside a trileaflet pulmonary valve. FIGURE II.6.9.3. Such autologous grafts can be compromised or be in short supply if the patient has had multiple procedures [10]. The DPA-eluting scaffold also supported endothelial cell growth, while inhibiting smooth muscle cell proliferation. 2012 Jul;18(7):394-404. doi: 10.1016/j.molmed.2012.04.013. Surprisingly, the use of cocultures with degradable PUs in cardiac TE systems has been limited when vascular grafts are excluded from the research. Dependence of a scaffold mechanical property (initial tensile modulus) on the bulk material mechanical property and scaffold structure. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as … This graft also showed similar mechanical properties with the native blood vessel. In the procedure of blood vessel tissue engineering, the operational stages are cell sources, cell culture, scaffolds, vessel bioreactors and implantation. 19.1). Greisler HP. The medial layer provides the mechanical integrity and the vasoactive response of the blood vessel. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. The goal was to determine the physical conditions necessary to make the cells grow, multiply and connect with each other so that a network of blood vessels assembled itself. COVID-19 is an emerging, rapidly evolving situation. Novel method to improve vascularization of tissue engineered constructs with biodegradable fibers. 2020 Feb 4;11:2041731420901621. doi: 10.1177/2041731420901621. This happens less frequently, and of course goes unnoticed, unless there is a significant loss of blood … The long culture times are also a problem in instances where “off-the-shelf” availability is desired. The phospholipid polymer (poly(methacryloyloxyethyl phosphorylcholine-co-acrylic acid), PMA, molar ratio = 70/30) was grafted onto the lumen of an electrospun PEUU conduit [38]. Fibroblasts are not always used in every approach, but can be used in the creation of an adventitial layer or in place of the smooth muscle cells to create the medial layer. Engineering blood vessels using stem cells: innovative approaches to treat vascular disorders. In an imaginary, modern remake of Fantastic Voyage, … Recent advances on nanotechnology have created new frontiers, terminologies, and possibilities which have led to breakthroughs in several distinct and multidisciplinary sciences. 861–1612. -. Description. Download Citation | On Jan 1, 2019, Wen Zeng and others published Tissue Engineering of Blood Vessels | Find, read and cite all the research you need on ResearchGate Although, it was observed that the smooth muscle cells were not fully contractile, these cellularized bilayer scaffolds showed great promise for tissue engineered vascular grafts, and a long-term animal study is expected. Cells were found to differentiate into a striated, contractile phenotype only on substrates within a very narrow range of muscle-like stiffness (i.e., 8–11 kPa) (Fig. Inhomogeneity is another important characteristic of natural tissues, which contain microdomains of distinct morphology and mechanical property to define tissue mechanics and mechanotransduction. Cardiac surgery. A continuous endothelial cell layer formed on the luminal surface. Muscle-derived stem cells and human pericytes were also seeded into this bilayer scaffold and then implanted into the rat aorta model. In an acellular graft, endothelial cells migrate no more than 1–2 cm into the graft (along the luminal surface), leaving the remainder of the graft exposed and prone to thrombosis; thrombosis is especially problematic in small diameter grafts where it often leads to significant stenosis or occlusion. There was improved hepatocyte function and the formation of luminal structures occurred within 3 days of coculture on the PU versus hepatocyte-only samples [102]. The coculture of HUVECs with HGFs was subsequently tested to see if HUVECs could vascularize the PU scaffolds. Figure II.6.9.3 shows a tissue-engineered blood vessel in a bioreactor capable of imparting cyclic strain, shear, and longitudinal extension (Zaucha et al., 2009). 8-11 kPa) (reproduced from Engler, Griffin et al. Fibroblasts secrete extracellular matrix (ECM) and have contractile apparatus, potentially allowing for the use of fibroblasts in place of smooth muscle cells. Areas of oscillatory or stagnant flow are prone to atherosclerotic plaques. New York: Churchill Livingstone; 1993. pp. In the next stage the cells will be located into scaffold and will be prepared for implantation, and the last stage is implantation into the human body. Culture of an engineered blood vessel in a bioreactor capable of luminal flow, cyclic strain, and axial stretch. This method can provide a blood-compatible surface without adverse effects on the PU conduit properties. Nonimmunogenic autologous endothelium cells and smooth muscle cells (tunica media area) isolated from patients are the first choice for vessel tissue engineering. The mechanical properties of the natural ECM are of paramount importance in dictating macroscopic tissue functions (e.g., bearing load) and regulating cellular behavior via mechanotransduction signaling. = 1.2 mm) [39].
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