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• W4245102772 abstract "Tissue engineered blood vessels are an attractive alternative to autologous vessels for the treatment of cardiovascular disease. In this issue of Matter, Jiang and colleagues developed an electronic blood vessel that integrated flexible electronics with biodegradable polymeric scaffold to expand its clinical applications. Tissue engineered blood vessels are an attractive alternative to autologous vessels for the treatment of cardiovascular disease. In this issue of Matter, Jiang and colleagues developed an electronic blood vessel that integrated flexible electronics with biodegradable polymeric scaffold to expand its clinical applications. Cardiovascular disease is the principle cause of mortality and morbidity across the world.1WHOWorld Health Statistics 2019: Monitoring health for the SDGs.https://www.who.int/gho/publications/world_health_statistics/2019/en/Date: 2019Google Scholar It is also one of the leading causes of death, which is estimated to result in 23.3 million annual death by 2030.2Criqui M.H. Aboyans V. Epidemiology of Peripheral Artery Disease.Circ. Res. 2015; 116: 1509-1526Crossref PubMed Scopus (909) Google Scholar The conventional surgical procedure to treat cardiovascular diseases is the coronary artery bypass graft (CABG), which can restore the normal blood flow. The first choice of the source of grafts is always autologous tissues, such as internal thoracic artery, saphenous vein, and radial artery.3Seifu D.G. Purnama A. Mequanint K. Mantovani D. Small-diameter vascular tissue engineering.Nat. Rev. Cardiol. 2013; 10: 410-421Crossref PubMed Scopus (338) Google Scholar However, the autologous vessels are often incompatible to use in patients and the harvesting process is associated with the high risk of morbidity, leading to the limitations of current CABGs. Tissue-engineered blood vessels (TEBVs) hold great promise to provide a considerable source for the future of vascular surgery.4Song H.G. Rumma R.T. Ozaki C.K. Edelman E.R. Chen C.S. Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise.Cell Stem Cell. 2018; 22: 340-354Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar In order to achieve biological and mechanical properties similar to those of the native tissues, researchers designed TEBVs based on different materials for clinical applications. Among them, the TEVGs fabricated using synthetic biodegradable polymers have attracted intensive attention for clinical-scale production owing to their wide availability and controllable properties. A variety of polymers have been tested and displayed good biocompatibility properties, including polyglycolic acid (PGA), poly-lactic acid (PLA), poly-L-lactic acid (PLLA), polyurethanes (PU), and polycaprolactone (PCL).5Ong C.S. Zhou X. Huang C.Y. Fukunishi T. Zhang H. Hibino N. Tissue engineered vascular grafts: current state of the field.Expert Rev. Med. Devices. 2017; 14: 383-392Crossref PubMed Scopus (49) Google Scholar Furthermore, scaffolds constructed from copolymers comprising two or more components are more feasible to meet the needs of mechanical properties for clinical translation through tuning the ratio of different components. Nonetheless, grafts made by synthetic polymers are usually unsatisfied for the requirement of biological properties due to the lack of bioactivity in synthetic polymeric scaffolds. To this end, living tissues, including multiple types of the blood vessel cells, are integrated with synthetic polymeric scaffolds to realize partial functions of natural blood vessel.6L’Heureux N. Dusserre N. Marini A. Garrido S. de la Fuente L. McAllister T. Technology insight: the evolution of tissue-engineered vascular grafts--from research to clinical practice.Nat. Clin. Pract. Cardiovasc. Med. 2007; 4: 389-395Crossref PubMed Scopus (238) Google Scholar Jiang and co-workers now report in Matter an electronic blood vessel that combined living tissues with flexible electronics in a synthetic polymeric scaffold (Figure 1).7Cheng S. Hang C. Ding L. Jia L. Tang L. Mou L. Qi J. Dong R. Zheng W. Zhang Y. et al.Electronic Blood Vessel.Matter. 2020; 3 (this issue): 1664-1684Abstract Full Text Full Text PDF Scopus (30) Google Scholar The blood vessel they developed not only contained three layers of blood vessel cells, but also possessed flexible electronics, which enables it achieve partial bioactivity of the natural blood vessel. For example, the endothelization process could be improved via electrical stimulation, and it is able to deliver genes into blood vessel cells by electroporation. Jiang and colleagues produced the electronical blood vessel via rolling up a metal-polymer conductor membrane made by the biodegradable polymer- poly(L-lactide-co-ε-caprolactone) (PLC) with liquid metal-based circuits. In order to mimic the structure of natural blood vessel, human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle cells (SMCs), human aortic fibroblasts (HAFs) were sequentially delivered on the membrane. Through a 14-day culture, three different cells were well distributed in different layers of the resulting electronic blood vessel, which also revealed the excellent biocompatibility of the vessel. They further demonstrated that direct current electric field could effectively facilitate the cell proliferation and migration, and the process was directly associated with the strength of electric field. Owing to the cooperation of flexible electronics, plasmid DNA was able to be delivered into the specific layer of blood vessel cells by electroporation. In addition, the further characterizations of the electronic blood vessel verified that most of its mechanical properties were similar or better than the native carotid artery. The authors also investigated the in vivo performance of the acellular electronic blood vessel in a rabbit model. In a 3-month implantation, the electronic blood vessel indicated good patency and biosafety in the vascular system monitored by doppler ultrasound imaging and arteriography. A further ex vivo study 3 months post-implantation confirmed its good biocompatibility in the rabbit model and its conductivity still maintained owning to the biocompatible liquid metal-based circuitry.8Yan J. Lu Y. Chen G. Yang M. Gu Z. Advances in liquid metals for biomedical applications.Chem. Soc. Rev. 2018; 47: 2518-2533Crossref PubMed Google Scholar To date, TEBVs are an attractive alternative to autologous vessels in CABGs for the treatment of cardiovascular disease. Researchers are currently investigating the production of TEBVs with the similar biological and mechanical properties compared with native blood vessels. Among them, challenges remain to realize biological functions in synthetic scaffolds. But the innovation in Jiang and colleagues’ work is to achieve partial biological functions by integrating flexible electronics with polymeric grafts. Studies of a 3-month implantation in a rabbit model demonstrated the designed TEBV had good performance and biocompatibility. Before entering clinical trials, a longer period of in vivo implantation and more detailed analysis are needed. Especially, it is important to address inflammation responses considering some increased inflammation markers during the 3-month implantation. The performance and biosafety of the electronics blood vessels with pre-cultured blood vessel cells are also required. Further studies integrated with other electronic components to explore applications between the vascular tissue and machine are promising for future personalized medicine. Electronic Blood VesselCheng et al.MatterOctober 1, 2020In BriefIntegrating bioelectronics and living tissues could enable powerful functionalities and capabilities to overcome biomedical problems. Here we introduce an electronic blood vessel that can integrate the conducting liquid metal-polymer circuitry with three layers of blood-vessel cells, to mimic and go beyond the natural blood vessel. With excellent biocompatibility and mechanical properties, it enables electrical stimulation and electroporation and exhibits great patency in a rabbit model. Full-Text PDF Open Archive" @default.
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