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WIREs Syst Biol Med
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Vascular tissue engineering: from in vitro to in situ

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Blood vessels transport blood to deliver oxygen and nutrients. Vascular diseases such as atherosclerosis may result in obstruction of blood vessels and tissue ischemia. These conditions require blood vessel replacement to restore blood flow at the macrocirculatory level, and angiogenesis is critical for tissue regeneration and remodeling at the microcirculatory level. Vascular tissue engineering has focused on addressing these two major challenges. We provide a systematic review on various approaches for vascular graft tissue engineering. To create blood vessel substitutes, bioengineers and clinicians have explored technologies in cell engineering, materials science, stem cell biology, and medicine. The scaffolds for vascular grafts can be made from native matrix, synthetic polymers, or other biological materials. Besides endothelial cells, smooth muscle cells, and fibroblasts, expandable cells types such as adult stem cells, pluripotent stem cells, and reprogrammed cells have also been used for vascular tissue engineering. Cell‐seeded functional tissue‐engineered vascular grafts can be constructed in bioreactors in vitro. Alternatively, an autologous vascular graft can be generated in vivo by harvesting the capsule layer formed around a rod implanted in soft tissues. To overcome the scalability issue and make the grafts available off‐the‐shelf, nonthrombogenic vascular grafts have been engineered that rely on the host cells to regenerate blood vessels in situ. The rapid progress in the field of vascular tissue engineering has led to exciting preclinical and clinical trials. The advancement of micro‐/nanotechnology and stem cell engineering, together with in‐depth understanding of vascular regeneration mechanisms, will enable the development of new strategies for innovative therapies. WIREs Syst Biol Med 2014, 6:61–76. doi: 10.1002/wsbm.1246 This article is categorized under: Developmental Biology > Stem Cell Biology and Regeneration Translational, Genomic, and Systems Medicine > Therapeutic Methods Translational, Genomic, and Systems Medicine > Translational Medicine

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Schematic illustration of in vitro, in vivo, and in situ tissue engineering of vascular grafts.
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Examples of vascular grafts and scaffolds made by using in vitro, in vivo, and in situ tissue engineering approaches. (a) Decellularized human iliac vein was recellularized with human autologous endothelial cells (ECs) and smooth muscle cells (SMCs) (courtesy of Suchitra Sumitran‐Holgersson). (b) Hematoxylin and eosin (H&E) staining reveals a decellularized internal membrane (IM), the fibroblast‐seeded living layer (LL) and the EC‐seeded lumen (L) of a tissue‐engineered vascular graft (TEVG) made by cell‐only approach. (c) H&E‐stained sections (arrow points to residual PGA) of a decellularized TEVG made in vitro by seeding cells in a PGA scaffold. Scale bar = 100 µm. (d) H&E staining of decellularized aortic graft seeded with ECs and SMCs reprogrammed from fibroblasts. (e) Electron micrograph of 2‐week granulation tissue formed in the rat peritoneal cavity by in vivo tissue engineering. Arrowhead indicates a mesothelial cell lining several layers of myofibroblasts. Magnification 3500×. (f) Scanning electron microscopy (SEM) of polycaprolactone–polyglycolic acid (PCL‐PLA) copolymer for clinical studies. Scale bar = 10 µm. (g) SEM images of composite grafts with a fast degrading inner layer. Scale bar = 100 µm. (h) Electrospun PLA graft immobilized with heparin and stromal cell‐derived factor‐1α (SDF‐1α; stained in red).
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Developmental Biology > Stem Cell Biology and Regeneration
Translational, Genomic, and Systems Medicine > Therapeutic Methods
Translational, Genomic, and Systems Medicine > Translational Medicine

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