A major disadvantage of a traditional sacrificial electrospinning approach is its inability to precisely control the size and the arrangement of the fibers during the electrospinning process, which after dissolution results in a random array of meso‐ and microchannels that are unlikely to mimic the structure of the natural capillary networks in human tissues. To mimic the natural vasculature in tissues, tissue‐engineered constructs should contain both meso‐ and microvasculature in a hierarchical system. CA: carotid artery, TIPSb)b) B) Decellularization of native tissues for microvasculature. 3D printing allows for the fabrication of anatomically accurate vascular grafts with predesigned pore size and porosity. A) Sequential rolling of multiple cell sheets. Therefore, using this method capillary networks can be made by first printing EC bioink droplets following a desired capillary network pattern using substrates such as hydrogels154 and porous scaffolds,155 where over time the ECs within droplets spread out and connect with those ECs in neighboring droplets to form capillary networks.154 Supporting cells can be added to stabilize the formed capillary network and prevent it from regression.154, 156 For example, electrospun PEUU cardiac patches printed with cell‐containing droplets in a capillary‐like grid pattern significantly improved angiogenesis following implantation in the infarcted zone of rat hearts compared to a control group implanted with randomly cell‐seeded patches. Springer Berlin Heidelberg. To obtain cell sheets, culture dishes are grafted with the thermal‐responsive polymer PNIPAM. For example, a 50 mm long graft was fabricated by extruding FB aggregates in between two concentric circles of supporting agarose gel, multiple layers were printed and subsequently, the cell aggregates in each layer fused to form an aortic ring‐like structure.122 However, the use of either FDM or bioink extrusion is limited when very soft materials, such as elastomers and hydrogels, are printed as the intended 3D structure is prone to collapse without supporting structures.122 In an effort to address this issue, a freeform reversible embedding of suspended hydrogels (FRESH) technique was developed, using a shear‐thinning gelatin slurry as a supporting hydrogel reservoir for the printed filaments.123 At the local printing point, due to the shear stress generated by the nozzle, the supporting gelatin hydrogel behaves as a fluid to allow the extrusion of the bioink. Decellularized animal and human tissues (Figure 6B) have been used as tissue‐engineered scaffolds.210 However, the preservation of both microvasculature and ECM in these tissues, following decellularization, has only been reported in a limited number of studies, which include the decellularization of skeletal muscle,211 adipose tissue,212 myocardium,213 and lung tissue.214 For example, a cardiac patch was developed from a decellularized porcine myocardium, which contained preserved vascular channels surrounded by a collagen network.213 The in vivo implantation of these scaffolds allowed the ingrowth of capillary networks from surrounding tissue which promoted tissue regeneration.215 However, limitations such as nonuniformity of seeded cells and poor cell interconnection remain to be the hurdles in the recellularization process.213 Also, the anastomosis of the BVs from the decellularized scaffold and the host are solely dependent on angiogenesis, preventing instantaneous perfusion. A) Electrospinning using single or blended polymer(s). In Biomaterials for Cardiac Regeneration (pp. Design template for tubular structures. C. The bioprinter (see Materials and Methods) outfitted with two vertically moving print heads. JavaScript is disabled for your browser. 49-79). The quest for an optimized protocol for whole-heart decellularization: a comparison of three popular and a novel decellularization technique and their diverse effects on crucial extracellular matrix qualities. Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. After printing, crosslinking of the alginate is achieved by the diffusion of Ca2+ from the core into the shell (Figure 3G).144 Following crosslinking, the core is removed through washing steps resulting in the instantaneous generation of mesochannels. Hydrogel scaffolds with elasticity-mimicking embryonic substrates promote cardiac cellular network formation. Bioprinting of artificial blood vessels: current approaches towards a demanding goal. Furthermore, the study showed the ability to transport biomolecules between adjacent unconnected microchannels (15 µm separation) through interstitial flow. This was then followed by UV crosslinking of the GelMA and PEGTA to form a stable structure. is the founding scientist of Elastagen Pty. The mechanical properties of a hydrogel scaffold such as its compressive modulus can affect the formation of vascular networks.232, 234 For example, HUVECs cocultured with apical papilla‐derived stem cells in GelMA hydrogels show higher tube formation efficiency with an improved compressive modulus.234 ECs and supporting cells are frequently cocultured with tissue‐specific types cells such as myofibroblasts,228 cardiomyocytes,235 and hepatocytes236 on scaffolds for the fabrication of functional vascularized tissues. acknowledges funding from the Australian Research Council and the National Health and Medical Research Council. Epub 2020 Jan 17. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. As an attractive approach, laser degradation is advantageous as it replicates the target tissue or organ microvasculature structure with high resolution using microscopy images as guidance and allows the incorporation of tissue‐specific cells in the gel. Droplet printing and SLA in 3D printing are predominantly used to generate microvasculature. June 2020; Tissue Engineering Part B Reviews; DOI: 10.1089/ten.TEB.2019.0264. PVA with different microsized patterns on the inner surface. With increased biomaterial degradation, cell infiltration, and tissue remodeling, the reduced mechanical properties must be compensated for by newly formed cellular components and synthesized extracellular matrix (ECM) without the development of aneurysms or intimal hyperplasia. The full text of this article hosted at iucr.org is unavailable due to technical difficulties. D) Cell sheet stacking for microvasculature. A–D) Fabrication of tissue‐engineered vascular graft. 3D bioprinting; CRISPR/Cas9; preclinical evaluation; stem cell; tissue-engineered vascular graft; vascular tissue engineering. MVGs with 2 µm grating patterns showed increased patent lumen area compared with unpatroned MVGs. 294-304. Scale bar: 100 μm. This study demonstrated a path toward the fabrication of a lung model by connecting multiple distal lung units with branching airways and mesovasculature. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. For example, studies have created mesochannels by melting and flushing molded gelatin embedded within collagen, fibrin, and Matrigel scaffolds,93 physically removing mesovasculature‐shaped PDMS rods from inside fibrin gels,94 and dissolving in water molded PVA that has been incorporated into porous hydrogels made from polymers such as 2‐hydroxyethyl methacrylate (HEMA), agarose, and methacrylated gelatin (GelMA).95 Importantly, the synthetic matrices in which the sacrificial mesovasculatures are embedded must allow for EC sprouting and remodeling in order to achieve successful integration with the host vasculature. Villalona GA(1), Udelsman B, Duncan DR, McGillicuddy E, Sawh-Martinez RF, Hibino N, Painter C, Mirensky T, Erickson B, Shinoka T, Breuer CK. In a sacrificial electrospinning approach, intertwined electrospun PNIPAM microfibers with diameters ranging from 3 to 55 µm were produced as sacrificial materials to generate interconnected microchannels (Figure 9C).73 Two 1.3 mm diameter PNIPAM rods were attached to the microfibers and after sacrifice served as the inlet and outlet for perfusion. The process allows the fabrication of up to 10 layers with different internal grid aspect ratios resulting in the formation of a winding continuous single mesochannel. Sie können mit Hilfe Ihres Browsers größer oder kleiner anzeigen lassen. Whole-Heart Tissue Engineering: Use of Three-Dimensional Matrix Scaffolds. USA.gov. Numerous reports have shown that acellular organs with preserved hierarchical vascular systems can be acquired through decellularization of whole organs (Figure 9B) such as heart,218, 259 lung,260 kidney,261 and liver.262 The retained structures of the BVs in these decellularized organs provide routes for the even distribution of ECs through perfusion.263 Apart from the intact vasculature, decellularized organs also offer mechanical support and biochemical and topological cues for cell migration, attachment, growth, differentiation, and function, but problems such as noncomplete endothelium and blood clotting remain the major hurdles for their applications.264 Recently, a partially decellularized lung where only the lung airway epithelium was removed has been developed, allowing the preservation of an intact endothelium‐containing vascular system with appropriate blood‐gas barrier function.265 However, immunosuppression would be necessary for this approach before complete remodeling and regeneration of the donor lung as the donor tissue still remains.

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