Zusammenfassung
Der prothetische Ersatz von Herzklappen und Gefäßen ist ein etabliertes Verfahren in der Chirurgie. Die derzeit erhältlichen Implantate haben jedoch eine Reihe von Nachteilen, beispielsweise eine begrenzte Haltbarkeit bei biologischen Herzklappen, die Anfälligkeit für Infektionen und die Notwendigkeit einer lebenslangen Antikoagulationstherapie bei künstlichen Herzklappen als auch eine reduzierte Offenheitsrate bei kleinkalibrigen Gefäßprothesen. Mit Hilfe des Tissue Engineering auf der Grundlage von Polymer- oder dezellularisierten biologischen Matrizes könnten in Zukunft ideale Herzklappen und Gefäße hergestellt werden. Die Matrix dient als Gerüst auf dem sich körpereigene Zellen entweder in vitro in einem Bioreaktor oder nach Implantation in vivo zu vaskulärem oder Herzklappengewebe entwickeln können. Die Matrix wird bei der Entstehung des neuen vitalen Gewebes entweder hydrolisiert oder metabolisiert. Diese Übersichtsarbeit fasst die aktuellen experimentellen und klinischen Konzepte zusammen.
Abstract
Current prosthetic substitutes for heart valves and blood vessels have numerous limitations such as limited durability (biological valves), susceptibility to infection, the necessity of lifelong anticoagulation therapy (prosthetic valves), and reduced patency in small-caliber grafts, for example. Tissue engineering using either polymers or decellularised native allogeneic or xenogenic heart valve/vascular matrices may provide the techniques to develop the ideal heart valve or vascular graft. The matrix scaffold serves as a basis on which seeded cells can organise and develop into the valve or vascular tissue prior to or following implantation. The scaffold is either degraded or metabolised during the formation and organisation of the newly generated matrix, leading to vital living tissue. This paper summarises current research and first clinical developments in the tissue engineering of heart valves and vascular grafts.
Notes
Die kranke Aortenklappe des Patienten wird durch die körpereigene Pulmonalklappe ersetzt. An deren Position wird der – ggf. dezellularisierte – Homograft implantiert.
Literatur
Richtlinie 2004/23/EG des Europäischen Parlaments und des Rates vom 31.03.2004 zur Festlegung von Qualitäts- und Sicherheitsstandards für die Spende, Beschaffung, Testung, Verarbeitung, Konservierung, Lagerung und Verteilung von menschlichen Geweben und Zellen (2004) In: Amtsblatt der Europäischen Union
Bader A, Schilling T, Teebken OE, Brandes G, Herden T, Steinhoff G, Haverich A (1998) Tissue engineering of heart valves--human endothelial cell seeding of detergent acellularized porcine valves. Eur J Cardiothorac Surg 14:279–284
Bader A, Steinhoff G, Strobl K et al. (2000) Engineering of human vascular aortic tissue based on a xenogeneic starter matrix. Transplantation 70:7–14
Barratt-Boyes BG (1965) A method for preparing and inserting a homograft aortic valve. B J Surg 52:847–856
Bechtel JFM, Schmidtke C, Mueller-Steinhardt M, Brunswik A, Stierle U, Sievers HH (2003) Evaluation of a decellularized homograft valve for reconstruction of the right ventricular outflow tract in the Ross-procedure. In: Second Biennal Meeting of the Society for Heart Valve Disease; 28.06.2003–01.07.2003; Palais des Congres — Porte Maillot, Paris, France, p 347
Bengtsson LA, Phillips R, Haegerstrand AN (1995) In vitro endothelialization of photooxidatively stabilized xenogeneic pericardium. Ann Thorac Surg 60:S365–368
Berglund JD, Mohseni MN, Nerem RM, Sambanis A (2003) Abiological hybrid model for collagen-based tissue engineered vascular constructs. Biomaterials 24:1241–1254
Bertipaglia B, Ortolani F, Petrelli L et al. (2003) Cell characterization of porcine aortic valve and decellularized leaflets repopulated with aortic valve interstitial cells. the VESALIO project (Vitalitate exornatum succedaneum aorticum laboringenioso obitenibitur). Ann Thorac Surg 75:1274–1282
Booth C, Korossis SA, Wilcox HE, Watterson KG, Kearney JN, Fisher J, Ingham E (2002) Tissue engineering of cardiac valve prostheses I: development and histological characterization of an acellular porcine scaffold. J Heart Valve Dis 11:457–462
Boyer M, Townsend LE, Vogel LM et al. (2000) Isolation of endothelial cells and their progenitor cells from human peripheral blood. J Vasc Surg 31:181–189
Carrier RL, Papadaki M, Rupnick M et al. (1999) Cardiac tissue engineering: Cell seeding, cultivation parameters, and tissue construct characterization. Biotechnol Bioeng 64:580–589
Cebotari S, Mertsching H, Kallenbach K et al. (2002) Construction of autologous human heart valves based on an acellular allograft matrix. Circulation 106 [Suppl 1]:I63–I68
Chue WL, Campbell GR, Caplicen et al. (2004) Dog peritoneal and pleural cavities as bioreactors to grow autologous vascular grafts. J Vasc Surg 39:859–867
Clarke DR, Lust RM, Sun YS, Black KS, Ollerenshaw JD (2001) Transformation of nonvascular acellular tissue matrices into durable vascular conduits. Ann Thorac Surg 71:S433–S436
Daly CD, Campbell GR, Walker PJ, Campbell JH (2004) In vivo engineering of blood vessels. Front Biosci 9:1915–1924
Davies MG, Hagen PO (1993) The vascular endothelium. Ann Surg 218:593–609
Deutsch M, Meinhart J, Fischlein T, Preiss P, Zilla P (1999) Clinical autologous in vitro endothelialization of infrainguinal ePTFE grafts in 100 patients: a 9-year experience. Surgery 126:847–855
Dohmen PM, Ozaki S, Verbeken E, Yperman J, Flameng W, Konertz WF (2002) Tissue engineering of an auto-xenograft pulmonary heart valve. Asian Cardiovasc Thoracic Ann 10:25–30
Edelman ER (1999) Vascular tissue engineering—designer arteries. Circ Res 85:1115–1117
Fischlein T, Fasol R (1996) In vitro endothelialization of bioprosthetic heart valves. J Heart Valve Dis 5:58–65
Fujisato Y, Numata S, Niwaya K, Kishida A, Yamada K, Nakatani T, Kitamura S (2003) In vitro endothelial cell seeding and expansion on 3d decellulariszed valve scaffold. In: The Society of Heart Valve Disease, Second biennal meeting; 28.06.2003–01.07.2003; Palais des Congres — Porte Maillot, Paris, France, p 84
Galbusera M, Zoja C, Donadelli R et al. (1997) Fluid shear stress modulates von Willebrand factor release from human vascular endothelium. Blood 90:1558–1564
Galletti PM, Aebischer P, Sasken HF, Goddard MB, Chiu TH (1988) Experience with fully bioresorbable aortic grafts in the dog. Surgery 103:231–241
Girton TS, Oegema TR, Grassl ED, Isenberg BC, Tranquillo RT (2000) Mechanisms of stiffening and strengthening in media-equivalents fabricate using glycation. J Biomech Eng 122:216–223
Greisler HP, Endean ED, Klosak JJ, Ellinger J, Dennis JW, Buttle K, Kim DU (1988) Polyglactin 910/polydioxanone bicomponent totally resorbable vascular prostheses. J Vasc Surg 7:697–705
Greisler HP, Kim DU, Dennis JW et al. (1987) Compound polyglactin 910/polypropylene small vessel prostheses. J Vasc Surg 5:572–583
Gulbins H, Goldemund A, Uhlig A, Pritisanac A, Meiser B, Reichart B (2003) Implantation of an autologously endothelialized homograft. J Thorac Cardiovasc Surg 126:890–891
Gulbins H, Kilian E, Roth S, Uhlig A, Kreuzer E, Reichart B (2002) Is there an advantage in using homografts in patients with acute infective endocarditis of the aortic valve? J Heart Valve Dis 11:492–497
Hoerstrup SP, Sodian R, Daebritz S et al. (2000) Functional living trileaflet heart valves grown In vitro. Circulation 102:III44–49
Hoerstrup SP, Sodian R, Sperling JS, Vacanti JP, Mayer JE Jr (2000) New pulsatile bioreactor for in vitro formation of tissue engineered heart valves. Tissue Eng 6:75–79
Hoerstrup SP, Zund G, Sodian R, Schnell AM, Grunenfelder J, Turina MI (2001) Tissue engineering of small caliber vascular grafts. Eur J Cardiothorac Surg 20:164–169
Jarrell BE, Williams SK, Rose D, Garibaldi D, Talbot C, Kapelan B (1991) Optimization of human endothelial cell attachment to vascular graft polymers. J Biomech Eng 113:120–122
Kadletz M, Magometschnigg H, Minar E, Konig G, Grabenwoger M, Grimm M, Wolner E (1992) Implantation of in vitro endothelialized polytetrafluoroethylene grafts in human beings. A preliminary report. J Thorac Cardiovasc Surg 104:736–742
Kadletz M, Moser R, Preiss P, Deutsch M, Zilla P, Fasol R (1987) In vitro lining of fibronectin coated PTFE grafts with cryopreserved saphenous vein endothelial cells. Thorac Cardiovasc Surg 35 (Spec No 2):143–147
Kaiser D, Freyberg MA, Schrimpf G, Friedl P (1999) Apoptosis induced by lack of hemodynamic forces is a general endothelial feature even occuring in immortalized cell lines. Endothelium 6:325–334
Kalmar P, Irrgang E (2003) Cardiac Surgery in Germany during 2002: A report by the German Society for Thoracic and Cardiovascular Surgery. Thorac Cardiovasc Surg 51:25–29
Koller MR, Papoutsakis ET (1995) Cell adhesion in animal cell culture: physiological and fluid-mechanical implications. Bioprocess Technol 20:61–110
L’Heureux N, Paquet S, Labbe R, Germain L, Auger FA (1998) A completely biological tissue-engineered human blood vessel. FASEB J 12:47–56
Lalka SG, Oelker LM, Malone JM et al. (1989) Acellular vascular matrix: a natural endothelial cell substrate. Ann Vasc Surg 3:108–117
Lantz GC, Badylak SF, Hiles MC et al. (1993) Small intestinal submucosa as a vascular graft: a review. J Invest Surg 6:297–310
Laube HR, Duwe J, Rutsch W, Konertz W (2000) Clinical experience with autologous endothelial cell-seeded polytetrafluoroethylene coronary artery bypass grafts. J Thoracic Cardiovasc Surg 120:134–141
Lehner G, Fischlein T, Baretton G, Murphy JG, Reichart B (1997) Endothelialized biological heart valve prostheses in the non-human primate model. Eur J Cardiothorac Surg 11:498–504
Leyh RG, Wilhelmi M, Rebe P, Fischer S, Kofidis T, Haverich A, Mertsching H (2003) In vivo repopulation of xenogenic and allogenic acellular valve matrix conduits in the pulmonary circulation. Ann Thorac Surg 75:1457–1463
Loose R, Schultze-Rhonhof U, Sievers HH, Bernhard A (1993) Preparing heart valve allografts for endothelial cell seeding. Transplant Proc 25:3244–3246
Malone JM, Brendel K, Duhamel RC, Reinert RL (1984) Detergent-extracted small-diameter vascular prostheses. J Vasc Surg 1:181–191
Martin U, Winkler ME, Id M et al. (2000) Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV). Xenotransplantation 7:138–142
Matsuda T, Miwa H (1995) A hybrid vascular model biomimicking the hirarchic structure of arterial wall: neointimal stability and neoarterial regeneration process under arterial circulation. J Thoracic Cardiovasc Surg 110:988–997
Matsumura G, Hibino N, Ikada Y, Kurosawa H, Shinoka T (2003) Successful application of tissue engineered vascular autografts: clinical experience. Biomaterials 24:2303–2308
Mazzucotelli JP, Moczar M, Zede L, Bambang LS, Loisance D (1994) Human vascular endothelial cells on expanded PTFE precoated with an engineered protein adhesion factor. Int J Artif Organs 17:112–117
Meng X, Mavromatis K, Galis ZS (1999) Mechanical stretching of human saphenous vein grafts induces expression and activation of matrix-degrading enzymes associated with vascular tissue injury and repair. Exp Mol Pathol 66:227–237
Miyata T, Conte MS, Trudell LA, Mason D, Whittemore AD, Birinyi LK (1991) Delayed exposure to pulsatile shear stress improves retention of human saphenous vein endothelial cells on seeded ePTFE grafts. J Surg Res 50:485–493
Nerem RM (2003) Role and mechanisms in vascular tissue engineering. Biorhology 40:281–364
Niklason LE, Abbott W, Gao J et al. (2001) Morphologic and mechanical characteristics of engineered bovine arteries. J Vasc Surg 33:628–638
Niklason LE, Gao J, Abbott WM, Hirschi KK, Houser S, Marini R, Langer R (1999) Functional arteries grown in vitro. Science 284:489–493
Niklason LE, Langer RS (1997) Advances in tissue engineering of blood vessels and other tissues. Transpl Immunol 5:303–306
O’Brien MF, Goldstein S, Walsh S, Black KS, Elkins R, Clarke D (1999) The SynerGraft valve: a new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization first experimental studies before clinical implantation. Semin Thorac Cardiovasc Surg 11:194–200
Opitz F, Schenke-layland K, Richter W, Martin DP, Degenkolbe I, Wahlers T, Stock UA (2004) Tissue engineering of ovine aortic blood vessel substitutes using applied shear stress and enzymatically derived vascular smooth muscle cells. Ann Biomed Eng 32:212–222
Pachence JM, Kohn J (1997) Biodegradable polymers for tissue engineering. In: Lanza RP, Langer R, Chick WP (eds) Principles of tissue engineering. Landes, Georgetown Texas USA, p 273–293
Pavcnik D, Uchida BT, Timmermans HA et al. (2002) Percutaneous bioprosthetic venous valve: A long-term study in sheep. J Vasc Surg 35:598–602
Pierschbacher MD, Polarek JW, Craig WS, Tschopp JF, Sipes NJ, Harper JR (1994) Manipulation of cellular interactions with biomaterials toward a therapeutic outcome: a perspective. J Cell Biochem 56:150–154
Ratto GB, Romano P, Truini M, Frascio M, Rovida S, Badini A, Zaccheo D (1991) Glutaraldehyde-tanned mandril-grown grafts as venous substitutes. J Thorac Cardiovasc Surg 102:440–447
Robotin-Johnson MC, Swanson PE, Johnson DC, Schuessler RB, Cox JL (1998) An experimental model of small intestinal submucosa as a growing vascular graft. J Thorac Cardiovasc Surg 116:805–811
Rosenberg N, Martinez A, Sawyer PN, Wesolowsky SA, Postlethwait RW, Dillon ML (1966) Tanned collagen arterial prosthesis of bovine carotid origin in man. Ann Surg 164:247
Ross D (1967) Homograft replacement of the aortic valve. B J Surg 54:842–843
Ross DN (1998) Options for right ventricular outflow tract reconstruction. J Card Surg 13:186–189
Schaner PJ, Martin ND, Tulenko TN et al. (2004) Decellularized veinas a potential scaffold for vascular tissue engineering. J Vasc Surg 40:146–153
Schenke-Layland K, Vasilevski O et al. (2003) Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. J Struct Biol 143:201–208
Schmidt CE, Baier JM (2000) Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering. Biomaterials 21:2215–2231
Schmidt SP, Hunter TJ, Sharp WV, Malindzak GS, Evancho MM (1984) Endothelial cell-seeded four-millimeter Dacron vascular grafts: effects of blood flow manipulation through the grafts. J Vasc Surg 1:434–441
Seifalian AM, Salacinski HJ, Tiwari A, Edwards A, Bowald S, Hamilton G (2003) In vivo biostability of a poly(carbonate-urea)urethane graft. Biomaterials 24:2549–2557
Seifalian AM, Tiwari A, Hamilton G, Salacinski HJ (2002) Improving the clinical patency of prosthetic vascular and coronary bypass grafts: the role of seeding and tissue engineering. Artif Organs 26:307–320
Shen G, Tsung HC, Wu CF et al. (2003) Tissue engineering of blood vessels with endothelial cells differentiated from mouse embrionic stem cells. Cell Res 13:335–341
Shinoka T (2002) Tisue engineered heart valves: autologous cell seeding on biodegradable polymer scaffold. Artif Organs 26:402–406
Shinoka T, Breuer CK, Tanel RE et al. (1995) Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann Thorac Surg 60: S513–516
Shinoka T, Shum-Tim D, Ma PX et al. (1998) Creation of viable pulmonary artery autografts through tissue engineering. J Thorac Cardiovasc Surg 115:536–545; discussion 545–536
Shirota T, He H, Yasui H, Matsuda T (2003) Human endothelial progenitor cell-seeded hybrid graft. Proliferative and antithrombogenic potentials in vitro and fabrication processing. Tissue Eng 9:127–136
Shum-Tim D, Stock U, Hrkach J et al. (1999) Tissue engineering of autologous aorta using a new biodegradable polymer. Ann Thorac Surg 68:2298–2304
Simon P, Kasimir MT, Seebacher G et al. (2003) Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. Eur J Cardiothorac Surg 23:1002–1006
Sipehia R, Martucci G, Lipscombe J (1996) Transplantation of human endothelial cell monolayer on artificial vascular prosthesis: the effect of growth-support surface chemistry, cell seeding density, ECM protein coating, and growth factors. Artif Cells Blood Substit Immobil Biotechnol 24:51–63
Skalak R, Fox C (1988) Tissue Engineering. In: Skalak R, Fox C (eds) Workshop on Tissue Engineering; 1988 26.–29.02.1988; Granlibakken, Lake Tahoe, CA, USA: Liss, New York, NY, USA
Sodian R, Hoerstrup SP, Sperling JS et al. (2000) Early In vivo experience with tissue-engineered trileaflet heart valves. Circulation 102:III22–29
Sparks CH (1973) Silicone mandril method for growing reinforced autogenous femoro-popliteal artery grafts in situ. Ann Surg 177:293–300
Steinhoff G, Stock U, Karim N et al. (2000) Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: In vivo restoration of valve tissue. Circulation 102:III50–55
Stock UA, Nagashima M, Khalil PN et al. (2000) Tissue-engineered valved conduits in the pulmonary circulation. J Thorac Cardiovasc Surg 119:732–740
Sung HW, Hsu CS, Chen HC, Hsu HL, Chang Y, Lu JH, Yang PC (1997) Fixation of various porcine arteries with an epoxy compound. Artif Organs 21:50–58
Tamura N, Nakamura T, Terai H, Iwakura A, Nomura S, Shimizu Y, Komeda M (2003) A new acellular vascular prosthesis as a scaffold for host tissue regeneration. Int J Artif Organs 26:783–792
Teebken OE, Bader A, Steinhoff G, Haverich A (1998) Ein neues Konzept für Ersatzmaterialien in der Gefäßchirurgie [A new concept for substitutes in vascular surgery]. Langenbecks Arch Chir Suppl Kongressbd 115:1256–1259
Teebken OE, Bader A, Steinhoff G, Haverich A (2000) Tissue engineering of vascular grafts: human cell seeding of decellularised porcine matrix. Eur J Vasc Endovasc Surg 19:381–386
Teebken OE, Haverich A (2002) Tissue Engineering of small diameter vascular grafts. Eur J Vasc Endovasc Surg 23:475–485
Teebken OE, Mertsching H, Haverich A (2002) Modification of heart valve allografts and xenografts by means of tissue engineering. Transplant Proc 34:2333
Teebken OE, Pichlmaier AM, Haverich A (2001) Cell seeded decellularised allogeneic matrix grafts and biodegradable polydioxanone-prostheses compared with arterial autografts in a porcine model. Eur J Vasc Endovasc Surg 22:139–145
Teebken OE, Puschmann C, Aper T, Haverich A, Mertsching H (2003) Tissue-engineered bioprosthetic venous valve: a long-term study in sheep. Eur J Vasc Endovasc Surg 25:305–312
Tiwari A, Salacinski H, Seifalian AM, Hamilton G (2002) New prostheses for use in bypass grafts with special emphasis on polyurethanes. Cardiovas Surg 10:191–197
Tiwari A, Salacinski HJ, Hamilton G, Seifalian AM (2001) Tissue engineering of vascular bypass grafts: role of endothelial cell extraction. Eur J Vasc Endovasc Surg 21:193–201
van Wachem PB, Stronck JW, Koers-Zuideveld R, Dijk F, Wildevuur CR (1990) Vacuum cell seeding: a new method for the fast application of an evenly distributed cell layer on porous vascular grafts. Biomaterials 11:602–606
Walluscheck KP, Steinhoff G, Haverich A (1996) Endothelial cell seeding of de-endothelialised human arteries: improvement by adhesion molecule induction and flow-seeding technology. Eur J Vasc Endovasc Surg 12:46–53
Walluscheck KP, Steinhoff G, Haverich A (1996) Endothelial cell seeding of native vascular surfaces. Eur J Vasc Endovasc Surg 11:290–303
Walluscheck KP, Steinhoff G, Kelm S, Haverich A (1996) Improved endothelial cell attachment on ePTFE vascular grafts pretreated with synthetic RGD-containing peptides. Eur J Vasc Endovasc Surg 12:321–330
Weinberg CB, Bell E (1986) A blood vessel model constructed from collagen and cultured vascular cells. Science 231:397–400
Williams SK, Jarrell BE (1996) Tissue engineered vascular grafts. Nature Medicine 2:32–34
Wilson GJ, Courtman DW, Klement P, Lee JM, Yeger H (1995) Acellular matrix: a biomaterials approach for coronary artery bypass and heart valve replacement. Ann Thorac Surg 60:S353–358
Wilson GJ, Yeger H, Klement P, Lee JM, Courtman DW (1990) Acellular matrix allograft small caliber vascular prostheses. ASIAO Transactions 36:M340-M343
Wu MHD, Shi Q, Wechezak AR, Clowes AW, Gordon IL, Sauvage LR (1995) Definitive proof of endothelialization of a Dacron arterial prosthesis in a human being. J Vasc Surg 21:862–867
Yacoub M, Rasmi NR, Sundt TM et al. (1995) Fourteen-year experience with homovital homografts for aortic valve replacement. J Thorac Cardiovasc Surg 110:186–193
Ye Q, Zund G, Jockenhoevel S, Hoerstrup SP, Schoeberlein A, Grunenfelder J, Turina M (2000) Tissue engineering in cardiovascular surgery: new approach to develop completely human autologous tissue. Eur J Cardiothorac Surg 17:449–454
Zund G, Breuer CK, Shinoka T, Ma PX, Langer R, Mayer JE, Vacanti JP (1997) The in vitro construction of a tissue engineered bioprosthetic heart valve. Eur J Cardiothorac Surg 11:493–497
Zund G, Hoerstrup SP, Schoeberlein A, Lachat M, Uhlschmid G, Vogt PR, Turina M (1998) Tissue engineering: a new approach in cardiovascular surgery: Seeding of human fibroblasts followed by human endothelial cells on resorbable mesh. Eur J Cardiothorac Surg 13:160–164
Interessenkonflikt:
Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Teebken, O.E., Wilhelmi, M. & Haverich, A. Tissue Engineering für Herzklappen und Gefäße. Chirurg 76, 453–466 (2005). https://doi.org/10.1007/s00104-005-1032-z
Issue Date:
DOI: https://doi.org/10.1007/s00104-005-1032-z