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Construction of Small Diameter Tissue Engineering Blood Vessels by Coaxial Printing |
SONG Biao-biao1,GU Qi1,2,3,**() |
1 School of Life Science, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China 2 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China |
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Abstract Currently, with the severity of population aging, cardiovascular disease(CVD) brings about health problems and unbearable economic burdens. In ischemic illnesses caused by the damage of small-diameter blood vessels, blood vessel transplantation has become an effective solution to tackle this challenge. However, small-diameter blood vessels are currently in high demand. Therefore, it is pretty crucial to construct small-diameter tissue-engineered blood vessels (TEBV) using tissue engineering methods. With the advancement of tissue engineering and 3D printing technology, the research of vascular grafts has developed rapidly. At present, most of the vascular graft materials used for large-diameter vascular grafts are polyester and polytetrafluoroethylene (PTFE). However, it is not applicable for the fabrication of small-diameter TEBV, in which case a myriad of unavoidable problems may come alone, such as inflammation and thrombosis. At the same time, current TEBV has such limitations as insufficient mechanical properties, which seriously hinder the clinical translation of TEBV. Therefore, in this experiment, we independently synthesized methacrylated gelatin (GelMA) and RGD-modified sodium alginate (RGD-Alginate) combined to form a double cross-linking system. By adding xanthan gum, the printability of the system is guaranteed. We used coaxial printing to fabricate a tube-like structure. Hybrid material system was characterized by a low vacuum cryo-scanning electron microscope. We found honeycomb-like forms appear on the surface, indicating that oxygen and nutrients could be provided to the cells in the tube through penetration. As for the selection of materials, the sacrificial material in the inner layer is 25% Pluronic F127 dissolved in 2% calcium chloride (CaCl2), and the outer material is 4% RGD-Alginate+5% GelMA+2% Xanthan Gum. During the printing process, the extrusion pressure of the printer is related to the diameter of the selected coaxial nozzles. When the 18G/14G coaxial nozzle is applied, the printing pressure is 55 kPa, and the printing speed is 5 mm/s. The syringe pump is utilized to extrude the material of the outer layer, whose speed is 264 μL/min. In the printing procedure, we selected two nozzles with different diameters to effectively fabricate a tube matching the nozzle diameter. In addition, a device for detecting burst pressure was established, which uses constant extrusion of the syringe pump to provide stable pressure to the tested tube. It has been demonstrated that the burst pressure is 328 mmHg±14 mmHg, which is quite different from the burst pressure of natural blood vessels in vivo. At the same time, it is sufficient to bear the vascular pressure in the physiological state of the human body. Human umbilical vein endothelial cells (HUVECs) were perfused into the tube-like structure (cell concentration was 1×107/mL). Through the imaging characterization of the cell state in the tube-like structure, it was found that HUVECs can be stably attached to the inner wall of a fabricated tube-like structure.
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Received: 23 April 2021
Published: 08 November 2021
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Corresponding Authors:
Qi GU
E-mail: qgu@ioz.ac.cn
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[1] |
Perk J, de Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Atherosclerosis, 2012, 223(1): 1-68.
doi: 10.1016/j.atherosclerosis.2012.05.007
|
|
|
[2] |
Song H H G, Rumma R T, Ozaki C K, et al. Vascular tissue engineering: progress, challenges, and clinical promise. Cell Stem Cell, 2018, 22(3): 340-354.
doi: 10.1016/j.stem.2018.02.009
|
|
|
[3] |
Mozaffarian D, Benjamin E J, Go A S, et al. Executive summary: heart disease and stroke statistics-2016 update: a report from the American heart association. Circulation, 2016, 133(4): 447-454.
doi: 10.1161/CIR.0000000000000366
pmid: 26811276
|
|
|
[4] |
Kunlin J. Long vein transplantation in treatment of ischemia caused by arteritis. Revue de Chirurgie, 1951, 70(7-8): 206-235.
|
|
|
[5] |
Nugent H M, Edelman E R. Tissue engineering therapy for cardiovascular disease. Circulation Research, 2003, 92(10): 1068-1078.
pmid: 12775655
|
|
|
[6] |
Hasan A, Memic A, Annabi N, et al. Electrospun scaffolds for tissue engineering of vascular grafts. Acta Biomaterialia, 2014, 10(1): 11-25.
doi: 10.1016/j.actbio.2013.08.022
|
|
|
[7] |
Nair L S, Laurencin C T. Biodegradable polymers as biomaterials. Progress in Polymer Science, 2007, 32(8-9): 762-798.
doi: 10.1016/j.progpolymsci.2007.05.017
|
|
|
[8] |
Weinberg C B, Bell E. A blood vessel model constructed from collagen and cultured vascular cells. Science, 1986, 231(4736): 397-400.
pmid: 2934816
|
|
|
[9] |
Ayala P, Dai E B, Hawes M, et al. Evaluation of a bioengineered construct for tissue engineering applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2018, 106(6): 2345-2354.
doi: 10.1002/jbm.b.v106.6
|
|
|
[10] |
Quint C, Arief M, Muto A, et al. Allogeneic human tissue-engineered blood vessel. Journal of Vascular Surgery, 2012, 55(3): 790-798.
doi: 10.1016/j.jvs.2011.07.098
pmid: 22056286
|
|
|
[11] |
Lawson J H, Glickman M H, Ilzecki M. Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials. Lancet, 2016, 387(10032): 2026-2034.
doi: 10.1016/S0140-6736(16)00557-2
|
|
|
[12] |
L’Heureux N, Dusserre N, Konig G, et al. Human tissue-engineered blood vessels for adult arterial revascularization. Nature Medicine, 2006, 12(3): 361-365.
doi: 10.1038/nm1364
|
|
|
[13] |
Galili U. The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. Immunology and Cell Biology, 2005, 83(6): 674-686.
pmid: 16266320
|
|
|
[14] |
Kim G, Ahn S, Kim Y, et al. Coaxial structured collagen-alginate scaffolds: fabrication, physical properties, and biomedical application for skin tissue regeneration. Journal of Materials Chemistry, 2011, 21(17): 6165-6172.
doi: 10.1039/c0jm03452e
|
|
|
[15] |
Kjar A, McFarland B, Mecham K, et al. Engineering of tissue constructs using coaxial bioprinting. Bioactive Materials, 2021, 6(2): 460-471.
doi: 10.1016/j.bioactmat.2020.08.020
|
|
|
[16] |
Zeng Z W, Hu C S, Liang Q F, et al. Coaxial-printed small-diameter polyelectrolyte-based tubes with an electrostatic self-assembly of heparin and YIGSR peptide for antithrombogenicity and endothelialization. Bioactive Materials, 2021, 6(6): 1628-1638.
doi: 10.1016/j.bioactmat.2020.10.028
|
|
|
[17] |
Liang Q F, Gao F, Zeng Z W, et al. Coaxial scale-up printing of diameter-tunable biohybrid hydrogel microtubes with high strength, perfusability, and endothelialization. Advanced Functional Materials, 2020, 30(43): 2001485.
doi: 10.1002/adfm.v30.43
|
|
|
[18] |
Kuo C K, Ma P X. Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1, structure, gelation rate and mechanical properties. Biomaterials, 2001, 22(6): 511-521.
pmid: 11219714
|
|
|
[19] |
Fu S, Thacker A, Sperger D M, et al. Relevance of rheological properties of sodium alginate in solution to calcium alginate gel properties. AAPS PharmSciTech, 2011, 12(2): 453-460.
doi: 10.1208/s12249-011-9587-0
|
|
|
[20] |
Jørgensen T E, Sletmoen M, Draget K I, et al. Influence of oligoguluronates on alginate gelation, kinetics, and polymer organization. Biomacromolecules, 2007, 8(8): 2388-2397.
pmid: 17602585
|
|
|
[21] |
Jia J, Richards D J, Pollard S, et al. Engineering alginate as bioink for bioprinting. Acta Biomaterialia, 2014, 10(10): 4323-4331.
doi: 10.1016/j.actbio.2014.06.034
pmid: 24998183
|
|
|
[22] |
Liu Y X, Chan-Park M B. A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture. Biomaterials, 2010, 31(6): 1158-1170.
doi: 10.1016/j.biomaterials.2009.10.040
|
|
|
[23] |
Van den Steen P E, Dubois B, Nelissen I, et al. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Critical Reviews in Biochemistry and Molecular Biology, 2002, 37(6): 375-536.
doi: 10.1080/10409230290771546
|
|
|
[24] |
Bertassoni L E, Cecconi M, Manoharan V, et al. Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab on a Chip, 2014, 14(13): 2202-2211.
doi: 10.1039/c4lc00030g
pmid: 24860845
|
|
|
[25] |
Nemeth C L, Janebodin K, Yuan A E, et al. Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels. Tissue Engineering Part A, 2014, 20(21-22): 2817-2829.
doi: 10.1089/ten.tea.2013.0614
|
|
|
[26] |
de Eke G, de Mangir N, Hasirci N, et al. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials, 2017, 129: 188-198.
doi: 10.1016/j.biomaterials.2017.03.021
|
|
|
[27] |
Navaei A, Saini H, Christenson W, et al. Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs. Acta Biomaterialia, 2016, 41: 133-146.
doi: 10.1016/j.actbio.2016.05.027
pmid: 27212425
|
|
|
[28] |
Yue K, Trujillo-de Santiago G, Alvarez M M, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 2015, 73: 254-271.
doi: 10.1016/j.biomaterials.2015.08.045
|
|
|
[29] |
Gao G, Lee J H, Jang J, et al. Tissue engineered bio-blood-vessels constructed using a tissue-specific bioink and 3D coaxial cell printing technique: a novel therapy for ischemic disease. Advanced Functional Materials, 2017, 27(33): 1700798.
doi: 10.1002/adfm.201700798
|
|
|
[30] |
Gao G, Park W, Kim B S, et al. Construction of a novel in vitro atherosclerotic model from geometry-tunable artery equivalents engineered via in-bath coaxial cell printing. Advanced Functional Materials, 2021, 31(10): 2008878.
doi: 10.1002/adfm.v31.10
|
|
|
[31] |
Konig G, McAllister T N, Dusserre N, et al. Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery. Biomaterials, 2009, 30(8): 1542-1550.
doi: 10.1016/j.biomaterials.2008.11.011
|
|
|
[32] |
Galie P A, Nguyen D H T, Choi C K, et al. Fluid shear stress threshold regulates angiogenic sprouting. PNAS, 2014, 111(22): 7968-7973.
doi: 10.1073/pnas.1310842111
|
|
|
[33] |
Song J W, Munn L L. Fluid forces control endothelial sprouting. PNAS, 2011, 108(37): 15342-15347.
doi: 10.1073/pnas.1105316108
|
|
|
|
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