Calcification Resistance of Procyanidin-Treated Decellularized Porcine Aortic Valves In Vivo

Authors

  • Yang Liu
  • Weiyong Liu
  • Guocheng Sun
  • Xufeng Wei
  • Dinghua Yi

DOI:

https://doi.org/10.1532/HSF98.20081103

Abstract

Objectives: Conventional glutaraldehyde fixation is conducive to calcification of bioprosthetic tissues. The aim of this study was to test calcification resistance of procyanidin-treated decellularized porcine aortic valve in a rat model.

Materials and methods: We performed cross-linking of the decellularized porcine aortic heart valves by procyanidins and observed morphologic performance and examined the tensile strength and cross-linking index. Then we implanted subcutaneous samples of procyanidin cross-linking decellularized valves, glutaraldehyde cross-linking decellularized valves, and decellularized valves in rats. The retrieved grafts were stained with hematoxylin-eosin and von Kossa and were analyzed with scanning electron microscopy and x-ray energy dispersive spectroscopy (EDS) after 21 and 63 days.

Results: After decellularized and cross-linking pretreatment, the procyanidin cross-linked leaflets were soft and stretchable. In addition, the cellular components of the porcine aortic heart valve leaflets were completely removed, and the extracelluar matrix was maintained completely. Examination of tensile strength revealed a significantly higher tissue resistance to tension in procyanidin cross-linked tissue than in other tissues, including the glutaraldehyde group (P < .05), even though the extents of cross-linking of each group were roughly the same at approximately 90%. Histopathologic examination showed that the procyanidin cross-linked valve matrix had no significant calcification, and there were no calcium peaks in the EDS profile of procyanidin cross-linked samples in the 21-day and 63-day rat studies.

Conclusion: This study demonstrated that procyanidin cross-linked decellularized heart valves can resist calcification to some extent.

References

Aldini G, Carini M, Piccoli A, Rossoni G, Facino RM. 2003. Procyanidins from grape seeds protect endothelial cells from peroxynitrite damage and enhance endothelium-dependent relaxation in human artery: new evidence for cardio-protection. Life Sci 73:2883-98.nBechtel JF, Muller-Steinhardt M, Schmidtke C, Bruswik A, Stierle U, Sievers HH. 2003. Evaluation of the decellularized pulmonary valve homograft (SynerGraft). J Heart Valve Dis 12:734-9.nBernacca GM, Tobasnick G, Wheatley DJ. 1994. Dynamic in-vitro calcification of porcine aortic valves. J Heart Valve Dis 3:684-7.nBroyn T, Christensen O, Fossdal JE, Kordt KF, Kroese A, Myhre HO. 1986. Early complications with a new bovine arterial graft (Solcograft-P). Acta Chir Scand 152:263-6.nCebotari S, Mertsching H, Kallenbach K, et al. 2002. Construction of autologous human heart valves based on an acellular allograft matrix. Circulation 106(12 suppl 1):I-63-8.nCourtman DW, Pereira CA, Kashef V, McComb D, Lee JM, Wilson GJ. 1994. Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction. J Biomed Mater Res 28:655-66.nDongmo AB, Kamanyi A, Anchang MS, et al. 2001. Anti-inflammatory and analgesic properties of the stem bark extracts of Erythrophleum suaveolens (Caesalpiniaceae) Guillemin & Perrottet. J Ethnopharmacol 77:137-41.nFerrans VJ, Milei J, Ishihara T, Storino R. 1991. Structural changes in implanted cardiac valvular bioprostheses constructed of glycerol-treated human dura mater. Eur J Cardiothorac Surg 5:144-54.nGirardot JM, Girardot MN. 1996. Amide cross-linking: an alternative to glutaraldehyde fixation. J Heart Valve Dis 5:518-25.nHan B, Jaurequi J, Tang WB, Nimni ME. 2003. Proanthocyanidin: a natural crosslinking reagent for stabilizing collagen matrices. J Biomed Mater Res 65:118-24.nJayaprakasha GK, Selvi T, Sakariah KK. 2003. Antibacterial and anti-oxidant activities of grape (Vitis vinifera) seed extracts. Food Res Int 36:117-22.nLevy RJ, Schoen RJ, Levy JT, Nelson AC, Howard SL, Oshry LJ. 1983. Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats. Am J Pathol 113:143-55.nMako WJ, Vesely I. 1997. In-vivo and in-vitro models of calcification in porcine aortic valve cusps. J Heart Valve Dis 6:316-23.nNaimark WA, Pereira CA, Tsang K, Lee JM. 1995. HMDC crosslinking of bovine pericardial tissue: a potential role of the solvent environment in the design of bioprosthetic materials. J Mater Sci Mater Med 6:235-41.nNemes A, Acsady G, Fraefel W, et al. 1985. Application of a vascular graft material (Solcograft-P) in experimental surgery. Biomaterials 6:303-11.nOgino Y, Osada K, Nakamura S, Ohta Y, Kanda T, Sugano M. 2007. Absorption of dietary cholesterol oxidation products and their down-stream metabolic effects are reduced by dietary apple polyphenols. Lipids 42:151-61.nPacker L, Rimbach G, Virgili F. 1999. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus Maritima) bark, pycnogenol. Free Radic Biol Med 27:704-24.nPark KD, Yun JY, Han DK, et al. 1994. Chemical modification of implantable biologic tissue for anti-calcification. ASAIO J 40:M377-82.nPereira CA, Lee JM, Haberer SA. 1990. Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material. J Biomed Mater Res 24:345-61.nPettenazzo E, Deiwick M, Thiene G, et al. 2001. Dynamic in vitro calcification of bioprosthetic porcine valves: evidence of apatite crystallization. J Thorac Cardiovasc Surg 121:500-9.nPlumb GW, De Pascual-Teresa S, Santos-Buelga C, Cheynier V, Williamson G. 1998. Antioxidant properties of catechins and proantho-cyanidins: effect of polymerisation, galloylation and glycosylation. Free Radic Res 29:351-8.nRapoport HS, Connolly JM, Fulmer J, et al. 2007. Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate. Biomaterials 28:690-9.nSchinke T, McKee MD, Karsenty G. 1999. Extracellular matrix calcification: where is the action? Nat Genet 21:150-1.nSchmitz-Rixen T, Megerman J, Anderson JM, et al. 1991. Longterm study of a compliant biological vascular graft. Eur J Vasc Surg 5:149-58.nSchoen FJ. 1999. Future directions in tissue heart valves: impact of recent insights from biology and pathology. J Heart Valve Dis 8:350-8.nSchoen FJ, Levy RJ. 1999. Tissue heart valves: current challenges and future research perspectives. J Biomed Mater Res 47:439-65.nSchoen FJ, Levy RJ. 2005. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann Thorac Surg 79:1072-80.nSchoen FJ, Levy RJ, Nelson AC, Bernhard WF, Nashef A, Hawley M. 1985. Onset and progression of experimental bioprosthetic heart valve calcification. Lab Invest 52:523-32.nSchoen FJ, Tsao JW, Levy RJ. 1986. Calcification of bovine pericardium used in cardiac valve bioprostheses. Implications for mechanisms of bioprosthetic tissue mineralization. Am J Pathol 123:134-45.nSchmidt CE, Baier JM. 2000. Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering. Biomaterials 21:2215-31.nShahat AA, Cos P, De Bruyne T, et al. 2002. Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica. Planta Med 68:539-41.nSimionescu DT. 2004. Prevention of calcification in bioprosthetic heart valves: challenges and perspectives. Expert Opin Biol Ther 4:1971-85.nSimon P, Kasimir MT, Seebacher G. 2003. Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. Eur J Cardiothorac Surg 23:1002-6.nSugiyama H, Akazome Y, Shoji T, et al. 2007. Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption. J Agric Food Chem 55:4604-9.nValente M, Bortolotti U, Thiene G. 1985. Ultrastructural substrates of dystrophic calcification in porcine bioprosthetic valve failure. Am J Pathol 119:12-21.nWilson GJ, Courtman DW, Klement P, Lee JM, Yeger H. 1995. Acellular matrix: a biomaterials approach for coronary artery and heart valve replacement. Ann Thorac Surg 60(2 Suppl):S353-8.nZhai W, Chang J, Lin K, Wang J, Zhao Q, Sun X. 2006. Crosslinking of decellularized porcine heart valve matrix by procyanidins. Biomaterials 27:3684-90.nZhao J, Wang J, Chen Y, Agarwal R. 1999. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent. Carcinogenesis 20:1737-45.nZilla P, Brink J, Human P, Bezuidenhout D. 2008. Prosthetic heart valves: catering for the few. Biomaterials 29:385-406.n

Published

2009-02-20

How to Cite

Liu, Y., Liu, W., Sun, G., Wei, X., & Yi, D. (2009). Calcification Resistance of Procyanidin-Treated Decellularized Porcine Aortic Valves In Vivo. The Heart Surgery Forum, 12(1), E24-E29. https://doi.org/10.1532/HSF98.20081103

Issue

Section

Article