Abstract
Small diameter vascular graft is a clinical need in cardiovascular disease (CAD) and peripheral atherosclerotic diseases (PAD). Autologous graft has limitations in availability and harvesting surgery. To make luminal surface modification with heparin coating in xenogeneic small diameter vascular graft. We constructed a conduit from decellularized human saphenous vein (HSV) matrices in small diameter vascular graft (< 0.8 mm diameter). Luminal surface modification was done with heparin coating for transplantation in the rat femoral artery. Biocompatibility of conduit was checked in Chorioallantoic Membrane (CAM) assay and in vivo. The blood flow rate in conduit grafts was measured, and immuno-histological analysis was performed. CAM assay and in vivo biocompatibility test showed cellular recruitment in the HSV scaffold. Heparin binding was achieved on the luminal surface. After three months of transplantation surgery neo-intimal layer was formed in the graft. The graft was patent for two weeks after surgery. There were no statistically differences between blood flow rate in graft (at proximal end 0.5 ± 0.01 m/s and at distal end 0.4 ± 0.01 m/s (n = 6)) and native artery (0.6 ± 0.1 m/second, (n = 3)). Biomarkers of endothelial cells, medial smooth muscle cells, and angiogenesis were observed in the transplanted graft. Our study demonstrates that xenogeneic decellularized vascular grafts with surface modification with heparin coating could be useful for the replacement of small diameter vessels.
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Abbreviations
- CVD:
-
Cardiovascular disease
- PAD:
-
Peripheral arterial disease
- HSV:
-
Human saphenous vein
- ECM:
-
Extracellular matrix
- TEVG:
-
Tissue-engineered vascular graft
- SDS:
-
Sodium dodecyl sulfate
- DHSV:
-
Decellularized HSV
- DHSVS:
-
Decellularized HSV scaffold
- DHSVC:
-
Decellularized HSV conduit
- hDHSVC:
-
Heparin coated Decellularized HSV conduit
- H&E:
-
Hematoxylin and eosin
- MT:
-
Masson’s trichrome
- AB:
-
Alcian blue
- TB:
-
Toluidine blue
- CAM:
-
Chorioallantoic membrane
- GAG:
-
Glycosaminoglycan
- SEM:
-
Scanning electron microscope
- CBC:
-
Complete blood count
- PT:
-
Prothrombin time
- APTT:
-
Activated partial thromboplastin time
- TT:
-
Thrombin time
References
Allen KB, Adams JD, Badylak SF et al (2021) Extracellular matrix patches for endarterectomy repair. Front Cardiovasc Med 8:1–13. https://doi.org/10.3389/fcvm.2021.631750
Bai H, Wang M, Foster TR et al (2016) Pericardial patch venoplasty heals via attraction of venous progenitor cells. Physiol Rep 4:1–13. https://doi.org/10.14814/phy2.12841
Bai H, Lee JS, Hu H et al (2018) Transforming growth factor-β1 inhibits pseudoaneurysm formation after aortic patch angioplasty. Arterioscler Thromb Vasc Biol 38:195–205. https://doi.org/10.1161/ATVBAHA.117.310372
Bai H, Dardik A, Xing Y (2019) Decellularized carotid artery functions as an arteriovenous graft. J Surg Res 234:33–39. https://doi.org/10.1016/j.jss.2018.08.008
Borghi N, Lowndes M, Maruthamuthu V et al (2010) Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions. Proc Natl Acad Sci U S A 107:13324–13329. https://doi.org/10.1073/pnas.1002662107
Chen JP, Su CH (2011) Surface modification of electrospun PLLA nanofibers by plasma treatment and cationized gelatin immobilization for cartilage tissue engineering. Acta Biomater 7:234–243. https://doi.org/10.1016/j.actbio.2010.08.015
Chen SG, Ugwu F, Li WC et al (2021) Vascular tissue engineering: advanced techniques and gene editing in stem cells for graft generation. Tissue Eng Part B Rev 27(1):14–28
Cholas R, Salvatore L, Madaghiele M, Sannino A (2017) Sterilization of collagen scaffolds designed for peripheral nerve regeneration : Effect on microstructure, degradation and cellular colonization. Mater Sci Eng C 71:335–344. https://doi.org/10.1016/j.msec.2016.10.030
De Mangir N, Dikici S, Claeyssens F, Macneil S (2019) Using ex ovo chick chorioallantoic membrane (CAM) assay to evaluate the biocompatibility and angiogenic response to biomaterials. ACS biomater Eng. https://doi.org/10.1021/acsbiomaterials.9b00172
Du J, Chen X, Liang X et al (2011) Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity. Proc Natl Acad Sci U S A 108:9466–9471. https://doi.org/10.1073/pnas.1106467108
Edenfield L, Blazick E, Eldrup-Jorgensen J et al (2020) Outcomes of carotid endarterectomy in the vascular quality initiative based on patch type. J Vasc Surg 71:1260–1267. https://doi.org/10.1016/j.jvs.2019.05.063
Fang S, Riber SS, Hussein K et al (2020) Decellularized human umbilical artery: biocompatibility and in vivo functionality in sheep carotid bypass model. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2020.110955
Gaudino M, Benedetto U, Fremes S et al (2020) Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. JAMA 324:179–187. https://doi.org/10.1001/jama.2020.8228
Gui L, Muto A, Chan SA et al (2009) Development of decellularized human umbilical arteries as small-diameter vascular grafts. Tissue Eng Part A 15:2665–2676. https://doi.org/10.1089/ten.tea.2008.0526
Guidoin R, Chakfé N, Maurel S et al (1993) Expanded polytetrafluoroethylene arterial prostheses in humans: histopathological study of 298 surgically excised grafts. Biomaterials 14:678–693. https://doi.org/10.1016/0142-9612(93)90067-C
Guruswamy Damodaran R, Vermette P (2018) Tissue and organ decellularization in regenerative medicine. Biotechnol Prog 34:1494–1505. https://doi.org/10.1002/btpr.2699
Horakova J, Mikes P, Saman A et al (2018) The effect of ethylene oxide sterilization on electrospun vascular grafts made from biodegradable polyesters. Mater Sci Eng C 92:132–142. https://doi.org/10.1016/j.msec.2018.06.041
Ingber D (1991) Extracellular matrix and cell shape: potential control points for inhibition of angiogenesis. J Cell Biochem 47:236–241. https://doi.org/10.1002/jcb.240470309
Ishii D, Enmi JI, Iwai R et al (2018) One year rat study of iBTA-induced “microbiotube” microvascular grafts with an ultra-small diameter of 0.6 mm. Eur J Vasc Endovasc Surg 55(6):882–887. https://doi.org/10.1016/j.ejvs.2018.03.011
Ji Y, Zhou J, Sun T et al (2019) Diverse preparation methods for small intestinal submucosa (SIS): decellularization, components, and structure. J Biomed Mater Res Part A 107:689–697. https://doi.org/10.1002/jbm.a.36582
Jiang B, Suen R, Wertheim JA, Ameer GA (2016) Targeting heparin to collagen within extracellular matrix significantly reduces thrombogenicity and improves endothelialization of decellularized tissues. Biomacromol 17:3940–3948. https://doi.org/10.1021/acs.biomac.6b01330
Ju YM, Ahn H, Arenas-Herrera J et al (2017) Electrospun vascular scaffold for cellularized small diameter blood vessels: a preclinical large animal study. Acta Biomater 59:58–67. https://doi.org/10.1016/j.actbio.2017.06.027
Kajbafzadeh AM, Khorramirouz R, Nabavizadeh B et al (2019) Whole organ sheep kidney tissue engineering and in vivo transplantation: effects of perfusion-based decellularization on vascular integrity. Mater Sci Eng C 98:392–400. https://doi.org/10.1016/j.msec.2019.01.018
Kirkton RD, Santiago-Maysonet M, Lawson JH et al (2019) Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation. Sci Transl Med 11:1–12. https://doi.org/10.1126/scitranslmed.aax7791
Komohara Y, Nakagawa T, Ohnishi K et al (2017) Optimum immunohistochemical procedures for analysis of macrophages in human and mouse formalin fixed paraffin-embedded tissue samples. J Clin Exp Hematop 57:31–36
Kong X, Kong C, Wen S, Shi J (2019) The use of heparin, bFGF, and VEGF 145 grafted acellular vascular scaffold in small diameter vascular graft. J Biomed Mater Res Part B Appl Biomater 107:672–679. https://doi.org/10.1002/jbm.b.34160
Konig G, Mcallister TN, Dusserre N et al (2009) Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery. Biomaterials 30:1542–1550. https://doi.org/10.1016/j.biomaterials.2008.11.011
Kuwabara F, Narita Y, Yamawaki-Ogata A et al (2012) Novel small-caliber vascular grafts with trimeric peptide for acceleration of endothelialization. Ann Thorac Surg 93:156–163. https://doi.org/10.1016/j.athoracsur.2011.07.055
Lapergola A, Felli E, Rebiere T et al (2020) Autologous peritoneal graft for venous vascular reconstruction after tumor resection in abdominal surgery: a systematic review. Updates Surg 72:605–615. https://doi.org/10.1007/s13304-020-00730-9
Lawson JH, Glickman MH, Ilzecki M et al (2016) Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials. Lancet 387:2026–2034. https://doi.org/10.1016/S0140-6736(16)00557-2
Li X, Jadlowiec C, Guo Y et al (2012) Pericardial patch angioplasty heals via an Ephrin-B2 and CD34 positive cell mediated mechanism. PLoS ONE. https://doi.org/10.1371/journal.pone.0038844
Liu RH, Ong CS, Fukunishi T et al (2018) Review of vascular graft studies in large animal models. Tissue Eng Part B Rev 24:133–143. https://doi.org/10.1089/ten.teb.2017.0350
Lopera Higuita M, Griffiths LG (2020) Small diameter xenogeneic extracellular matrix scaffolds for vascular applications. Tissue Eng Part B Rev 26:26–45. https://doi.org/10.1089/ten.teb.2019.0229
Lu X, Han L, Kassab GS (2019a) In vivo self-assembly of small diameter pulmonary visceral pleura artery graft. Acta Biomater 83:265–276. https://doi.org/10.1016/j.actbio.2018.11.001
Lu X, Han L, Kassab GS (2019b) Acta Biomaterialia In vivo self-assembly of small diameter pulmonary visceral pleura artery graft. Acta Biomater 83:265–276. https://doi.org/10.1016/j.actbio.2018.11.001
Mahara A, Sakuma T, Mihashi N et al (2019) Accelerated endothelialization and suppressed thrombus formation of acellular vascular grafts by modifying with neointima-inducing peptide: A time-dependent analysis of graft patency in rat-abdominal transplantation model. Colloids Surfaces B Biointerfaces 181:806–813. https://doi.org/10.1016/j.colsurfb.2019.06.037
Mallis P, Kostakis A, Stavropoulos-Giokas C, Michalopoulos E (2020) Future perspectives in small-diameter vascular graft engineering. Bioengineering 7:1–40. https://doi.org/10.3390/bioengineering7040160
Mangir N, Dikici S, Claeyssens F, Macneil S (2019) Using ex ovo chick chorioallantoic membrane (CAM) assay to evaluate the biocompatibility and angiogenic response to biomaterials. ACS Biomater Sci Eng 5:3190–3200. https://doi.org/10.1021/acsbiomaterials.9b00172
Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:2011–2030. https://doi.org/10.1371/journal.pmed.0030442
Matsuzaki Y, John K, Shoji T, Shinoka T (2019) The evolution of tissue engineered vascular graft technologies: from preclinical trials to advancing patient care. Appl Sci. https://doi.org/10.3390/app9071274
Mendonça MCP, Radaic A, Fossa FG et al (2019) Toxicity of cationic solid lipid nanoparticles in rats. J Phys Conf Ser 1323:1–18. https://doi.org/10.1088/1742-6596/1323/1/012016
Molina CP, Lee YC, Badylak SF (2020) Pancreas whole organ engineering. Elsevier Inc, New York
Murukesh N, Dive C, Jayson GC (2010) Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer 102:8–18. https://doi.org/10.1038/sj.bjc.6605483
Nakayama Y, Furukoshi M, Terazawa T (2019) Development of a long autologous small-caliber biotube vascular graft. Eur J Vasc Endovasc Surg 58:e121. https://doi.org/10.1016/j.ejvs.2019.06.661
Narayan J, Kumar P, Gupta A, Tiwari S (2018) To compare the blood pressure and heart rate during course of various types of anesthesia in wistar rat: a novel experiences. Asian J Med Sci 9:37–39. https://doi.org/10.3126/ajms.v9i6.20625
Nowygrod R, Egorova N, Greco G et al (2006) Trends, complications, and mortality in peripheral vascular surgery. J Vasc Surg 43:205–216. https://doi.org/10.1016/j.jvs.2005.11.002
Ong CS, Zhou X, Huang CY et al (2017) Tissue engineered vascular grafts: current state of the field. Expert Rev Med Devices 14:383–392. https://doi.org/10.1080/17434440.2017.1324293
Peng G, Yao D, Niu Y et al (2019) Surface modification of multiple bioactive peptides to improve endothelialization of vascular grafts. Macromol Biosci 19:1–12. https://doi.org/10.1002/mabi.201800368
Rajab TK, O’Malley TJ, Tchantchaleishvili V (2020) Decellularized scaffolds for tissue engineering: current status and future perspective. Artif Organs 44:1031–1043. https://doi.org/10.1111/aor.13701
Saha T, Naqvi SY, Ayah OA et al (2017) Subclavian artery disease: diagnosis and therapy. Am J Med 130(4):409–416. https://doi.org/10.1016/j.amjmed.2016.12.027
Schaner PJ, Martin ND, Tulenko TN et al (2004) Decellularized vein as a potential scaffold for vascular tissue engineering. J Vasc Surg 40:146–153. https://doi.org/10.1016/j.jvs.2004.03.033
Shaik TA, Alfonso-Garciá A, Zhou X et al (2020) FLIm-guided Raman imaging to study cross-linking and calcification of bovine pericardium. Anal Chem 92:10659–10667. https://doi.org/10.1021/acs.analchem.0c01772
Shibutani S, Obara H, Matsubara K et al (2020) Midterm results of a japanese prospective multicenter registry of heparin-bonded expanded polytetrafluoroethylene grafts for above-the-knee femoropopliteal bypass. Circ J 84:501–508. https://doi.org/10.1253/circj.CJ-19-0908
Skalli O, Pelte MF, Peclet MC et al (1989) α-Smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem 37:315–321. https://doi.org/10.1177/37.3.2918221
Song P, Rudan D, Zhu Y et al (2019) Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Heal 7:e1020–e1030. https://doi.org/10.1016/S2214-109X(19)30255-4
Sun KH, Chang Y, Reed NI, Sheppard D (2016) α-smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis. Am J Physiol Lung Cell Mol Physiol 310:L824–L836. https://doi.org/10.1152/ajplung.00350.2015
Tardalkar K, Desai S, Adnaik A et al (2017) Novel approach toward the generation of tissue engineered heart valve by using combination of antioxidant and detergent: a potential therapy in cardiovascular tissue engineering. Tissue Eng Regen Med 14:755–762. https://doi.org/10.1007/s13770-017-0070-1
Te KC, Su CM, Chang HW et al (2014) Serum adhesion molecules as outcome predictors in adult severe sepsis patients requiring mechanical ventilation in the emergency department. Clin Biochem 47:38–43. https://doi.org/10.1016/j.clinbiochem.2014.06.020
Tranbaugh RF, Schwann TA, Swistel DG et al (2017) Coronary artery bypass graft surgery using the radial artery, right internal thoracic artery, or saphenous vein as the second conduit. Ann Thorac Surg 104:553–559. https://doi.org/10.1016/j.athoracsur.2016.11.017
Wang M, Bao L, Qiu X et al (2018) Immobilization of heparin on decellularized kidney scaffold to construct microenvironment for antithrombosis and inducing reendothelialization. Sci China Life Sci 61:1168–1177. https://doi.org/10.1007/s11427-018-9387-4
Xenogiannis I, Gkargkoulas F, Karmpaliotis D et al (2020) Retrograde chronic total occlusion percutaneous coronary intervention via saphenous vein graft. JACC Cardiovasc Interv 13:517–526. https://doi.org/10.1016/j.jcin.2019.10.028
Yamanaka H, Yamaoka T, Mahara A et al (2018) Tissue-engineered submillimeter-diameter vascular grafts for free flap survival in rat model. Biomaterials 179:156–163. https://doi.org/10.1016/j.biomaterials.2018.06.022
Zanetta L, Marcus SG, Vasile J et al (2000) Expression of von Willebrand factor, an endothelial cell marker, is up- regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis. Int J Cancer 85:281–288. https://doi.org/10.1002/(SICI)1097-0215(20000115)85:2%3C281::AID-IJC21%3E3.0.CO;2-3
Zhang YQ, Ma Y et al (2006) Synthesis of silk fibroin-insulin bioconjugates and their characterization and activities in vivo. J Biomed Mater Res Part B Appl Biomater 79(2):275–283. https://doi.org/10.1002/jbmb
Zhao Q, Zhu Y, Xu Z et al (2018) Effect of ticagrelor plus aspirin, ticagrelor alone, OR aspirin alone on saphenous vein graft patency 1 year after coronary artery bypass grafting: a randomized clinical trial. JAMA 319:1677–1686. https://doi.org/10.1001/jama.2018.3197
Acknowledgements
The authors are grateful to the Department of Botany, Shivaji University, Kolhapur for extending the SEM facility. Dr. Meghnad G. Joshi acknowledges the research funding support from the Department of Science and Technology (DST), Govt. of India (SB/SO/HS/0198/2013), and D.Y. Patil Education Society Deemed University (DYPES/DU/R&D/3104).
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MJ conceived the study and designed the experiments. KT, NB, TM performed the experiments. MJ reviewed, analyzed, and interpreted the data. MJ and KT wrote the manuscript. All authors contributed to the analysis of the data and discussed the manuscript.
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All experimental procedures in this study were approved by the Institutional Ethical Committee (IAEC) (Ref.-6/IAEC/2017), D Y Patil Education Society, Deemed University, Kolhapur, India and conducted in accordance with D Y Patil Education Society, Deemed University guidelines for the care and use of laboratory animals.
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Tardalkar, K.R., Marsale, T.B., Bhamare, N.C. et al. Heparin coated decellularized xenogeneic small diameter vascular conduit for vascular repair with early luminal reendothelialization. Cell Tissue Bank 24, 449–469 (2023). https://doi.org/10.1007/s10561-022-10046-0
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DOI: https://doi.org/10.1007/s10561-022-10046-0