Compatibility characteristics of acellular porcine heart valve matrix co-crosslinked with procyanidins and glutaraldehyde
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摘要: 采用8 mg/mL原花青素交联脱细胞猪主动脉心脏瓣膜4 h后,再经1.25 mg/mL戊二醛交联44 h.生物相容性检测结果显示,共交联瓣膜组细胞粘附率较戊二醛单独交联提高59%((78.758.7)%~(19.753.27)%)、无明显溶血现象((0.750.36)%)、血小板粘附量较戊二醛单独交联显著减少((19315.5)个 vs (292.624.93)个)、免疫原性低((49.336.3)% vs (95.275.26)%). 研究结果表明,共交联瓣膜材料有良好的细胞相容性、较好的血液相容性和较低的免疫原性,是一种优良的生物瓣材料,有望应用于生物瓣制备.Abstract: The clinical used bioprosthetic heart valves (BHVs) were prepared from biological tissues by glutaraldehyde (GA) crosslinking. But the clinical application of BHVs is limited mainly due to calcification, cytotoxicity and remaining immunogenicity. Procyanidins (PC) can crosslink acellular heart valve matrix (AHVM) through hydrogen bond formation and prevent AHVM from calcification. The aim of this study is to modify GA crosslinking method using PC co-crosslinking to produce a much ideal material with higher compatibility for BHV preparation. Porcine aortic AHVM was crosslinked by 8 mg/mL PC for 4 h and then by 1.25 mg/mL GA for 44 h. The co-crosslinked AHVM was tested for cytocompatibility, blood compatibility and immunogenicity. The results showed that the in vitro adhesion rate of valvular interstitial cells on co-crosslinked AHVM was increased by 59% (78.75%~19.75%)when compared with that of GA-crosslinking. There was no difference in hemolysis between co- and GA- or PC-crosslinked AHVM. The co-crosslinked AHVM exhibited significant anti-thrombosis effect ((19315.5) platelets) when compared with that of GA-crosslinked ((292.624.93) platelets). Furthermore, co-crosslinked AHVM displayed lower immunogenicity than that of GA-crosslinked ((49.336.3)% vs (95.275.26)%, cell adhesive rate). These results suggest that co-crosslinked AHVM has high potential to be used for preparation of BHVs.
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Key words:
- procyanidins /
- glutaraldehyde /
- crosslinking /
- heart valve matrix /
- compatibility
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[1] [1] JAYAKRISHNAN A, JAMEELA S R. Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices[J]. Biomaterials, 1996, 17: 471-484.[2] SCHOEN F J, LEVY R J. Tissue heart valves: Current challenges and future research perspectives[J]. J Biomed Mater Res, 1999, 47: 439-465.[3] CHANG Y, HSU C K, WEI H J, et al. Cell-free xenogenic vascular grafts fixed with glutaraldehyde or genipin: In vitro and in vivo studies[J]. J Biotechnol, 2005, 120: 207-219.[4] ZHAI W, L X, CHANG J, et al. Quercetin-crosslinked porcine heart valve matrix: Mechanical properties, stability, anticalcification and cytocompatibility[J]. Acta Biomater, 2010(6): 389-395.[5] SCHMIDT C E,BAIER J M. Acellular vascular tissues: Natural biomaterials for tissue repair and tissue engineering[J]. Biomaterials, 2000, 21: 2215-2231.[6] ISENBURG J C, SIMIONESCU D T,VYAVAHARE N R. Tannic acid treatment enhances biostability and reduces calcification of glutaraldehyde fixed aortic wall[J]. Biomaterials, 2005, 26: 1237-1245.[7] NORBERT W G, HANGORG Z, HANS H S. Nano-coating with titanium of glutaraldehyde-fixed heart valve prostheses enables a reduced immune response and a self-seeding within circulation[G]//DANIEL E. Regenerative Medicine and Tissue Engineering-Cells and Biomaterials. Rijeka: InTech,2011.[8] ZHAI W, CHANG J, LIN K, et al. Crosslinking of decellularized porcine heart valve matrix by procyanidins[J]. Biomaterials, 2006, 27: 3684-3690.[9] ZHAI W, CHANG J, L X, et al. Procyanidins-crosslinked heart valve matrix: Anticalcification effect[J]. J Biomed Mater Res B, 2009, 90B: 913-921.[10] FURIGA A, LONVAUD F, BADET C. In vitro study of antioxidant capacity and antibacterial activity on oral anaerobes of a grape seed extract[J]. Food Chem, 2009, 113: 1037-1040.[11] SIVAKUMARAN S, MOLAN A L, MEAGHER L P, et al. Variation in antimicrobial action of proanthocyanidins from Dorycnium rectum against rumen bacteria[J]. Phytochemistry, 2004, 65: 2485-2497. [12] SANO T, ODA E, YAMASHITA T, et al. Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seed[J]. Thromb Res, 2005, 115: 115-121.[13] LIU Y Z, CAO Y G, YE J Q, et al. Immunomodulatory effects of proanthocyanidin A-1 derived in vitro from Rhododendron spiciferum[J]. Fitoterapia, 2010, 81: 108-114.[14] JOHNSON C M, HANSON M N,HELGESON S C. Porcine cardiac valvular subendothelial cells in culture-cell isolation and growth-characteristics[J]. J Mol Cell Cardiol, 1987, 19: 1185-1193.[15] BRODBECK W G, NAKAYAMA Y, MATSUDA T, et al. Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro[J]. Cytokine, 2002, 18: 311-319.[16] 李相仕. 壳聚糖基生物材料与巨噬细胞相互作用研究[D]. 天津:天津大学,2007.[17] BLAZSO G, GABOR M,ROHDEWALD P. Antiinflammatory activities of procyanidin-containing extracts from Pinus pinaster Ait after oral and cutaneous application[J]. Pharmazie, 1997, 52: 380-382. [18] 刘兴光,汪钢,俞世强,等.组织工程心脏瓣膜支架材料的血液相容性[J].中国临床康复,2004,8(30):6659-6661.[19] ZHOU J Y, FRITZE O, SCHLEICHER M, et al. Impact of heart valve decellularization on 3-D ultrastructure, immunogenicity and thrombogenicity[J]. Biomaterials, 2010, 31: 2549-2554.[20] OKAMURA K, CHIBA C, IRIYAMA T, et al. Antigen depressant effect of glutaraldehyde for aortic heterografts with a valve, with special reference to a concentration right fit for the preservation of grafts[J]. Surgery, 1980, 87: 170-176.[21] SIMON P, KASIMIR M T, SEEBACHER G, et al. Early failure of the tissue engineered porcine heart valve SYNERGRAFT (TM) in pediatric patients[J]. Eur J Cardio-Thorac Sur, 2003, 23: 1002-1006.
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