Abstract
Cardiac tissue engineering has emerged as a promising approach to replace or support an infarcted cardiac tissue and thus may hold a great potential to treat and save the lives of patients with heart diseases. By its broad definition, tissue engineering involves the construction of tissue equivalents from donor cells seeded within 3-D biomaterials, then culturing and implanting the cell-seeded scaffolds to induce and direct the growth of new, healthy tissue. In this review, we present an up-to-date summary of the research in cardiac tissue engineering, with an emphasis on the design principles and selection criteria that have been used in two key technologies employed in tissue engineering, (1) biomaterials technology, for the creation of 3-D porous scaffolds which are used to support and guide the tissue formation from dissociated cells, and (2) bioreactor cultivation of the 3-D cell constructs during ex-vivo tissue engineering, which aims to duplicate the normal stresses and flows experienced by the tissues.
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References
American Heart Association. 2000 Heart and Stroke Statistical Update. Dallas, Texas: American Heart Association, 1999.
Eschenhagen T, Fink C, Remmers U, Scholz H, Wattchow J, Weil J, Zimmermann W, Dohmen HH, Schafer H, Bishopric N, Wakatsuki T, Elson EL. Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: A new heart muscle model system. FASEB J 1997;11:683- 694.
Akins Re, Boyce RA, Madonna ML, Schroedl NA, Gonda SR, Mclaughlin TA, Hartzell CR. Cardiac organogenesis in vitro: Reestablishment of three-dimensional tissue architecture by dissociated neonatal rat ventricular cells. Tissue Engineering 1999;5:103-118.
Carrier RL, Papadaki M, Rupnick M, Schoen FJ, Bursac N, Langer R, Freed LE, Vunjak-Novakovic G. Cardiac tissue engineering: Cell seeding, cultivation parameters, and tissue construct characterization. Biotech Bioeng 1999;64:580-589.
Leor J, Aboulafia-Etzion S, Dar A, Shapiro L, Barbash IM, Granot Y, Battler A, Cohen S. Bioengineered cardiac grafts to repair the infarcted myocardium and attenuate heart failure. Circulation 2000;102(Suppl III):III-56-III-61.
Li RK, Yau TM, Weisel RD, Mickle DAG, Sakai T, Choi A, Jia ZQ. Construction of a bioengineered cardiac graft. J Thorac Cardiovase Surg 2000;119:368-375.
Papadaki M, Bursac N, Langer R, Merok J, Vunjak-Novakovic G, Freed LE. Tissue engineering of functional 276 Shachar and Cohen cardiac muscle: Molecular, structural, and electrophysiological studies. Am J Physiol Heart Circ Physiol 2001;280:H168-H178.
Dar A, Shachar M, Leor J, Cohen S. Cardiac tissue engineering: Optimization of cardiac cell seeding and distribution in 3-D porous alginate scaffolds. Biotechnology & Bioengineering 2002;80:305-312.
Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920-926.
Perets A, Baruch Y, Spira G, Cohen S. Fabrication of alginate composites containing vascular endothelial growth factor to enhance scaffold vascularization. Proc 25th Intern Symp on Control Rel Bioact Mater. In: Park K, Potts RO, eds. CRS; 1998:225-226.
Richardson TP, Peters MC, Ennett AB, Mooney DJ. Polymeric system for dual growth factor delivery. Nature Biotech 2001;19:1029-1032.
Perets A, Baruch Y, Weisbuch F, Shoshany G, Neufeld G, Cohen S. Enhancing the vascularization of 3-D porous alginate scaffolds by incorporating controlled release bFGF microspheres. J Biomed Mater Res 2002;6519:489-497.
Vacanti JP, Langer R. Tissue engineering: The design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 1999;354:32-34.
Pachence JM, Kohn J. Biodegradable polymers for Tissue Engineering. Principles of Tissue Engineering. In: Lanza RP, Langer R, Chick WL, eds. Landes Biosciences Academic Press. 1997:273-293.
Kim BS, Mooney DJ. Engineering smooth muscle tissue with a pre-defined structure. J Biomed Mater Res 1998;41:322-332.
Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP, Langer R. Prevascularization of porous biodegradable polymers. Biotechnol Bioeng 1993;42:716-723.
Bostman OE, Hirvensalo E, Makinen J, Rokkanen P. Foreign-body reactions to fracture fixation implants of biodegradable synthetic polymers. J Bone Joint Surg 1990;72-B:592-596.
Krupnick AS, Shabaan A, Radu A, Flake AW. Bone marrow tissue engineering. Tissue Eng 2002;8:145-155.
Ben-Yishay A, Grande DA, Schwartz RE, Mneche D, Pitman MS. Repair of articular cartilage defects with collagen-chondrocytes allografts. Tissue Eng 1995;1:119- 132.
Olde Damink LHH, Dijkstra PJ, Van Luyn MJA, Van Wachem PB, Nieuwenhuis P, Feijen J. Changes in the mechanical properties of dermal sheep collagen during in vitro degradation. J Biomed Mater Res 1995;20:139-145.
Shapiro L, Cohen S. Novel alginate sponges for cell culture and transplantation. Biomaterials 1997;18: 583-590.
Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 1999;20:45-53.
Zmora S, Glicklis R, Cohen S. Tailoring the pore architecture of 3-D alginate scaffolds by controlling the freezing regime during fabrication. Biomaterials 2002;23:4087- 4094.
Glicklis R, Shapiro L, Agbaria R, Merchuk JC, Cohen S. Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol Bioeng 2000;67:344- 353.
Miller WM. Bioreactor design considerations for cell therapies and tissue engineering. In:WTECWorkshop on Tissue Engineering Research in the United States. Proceedings. Baltimore, MD: International Technology Research Institute, Loyola College, June 5, 2000.
Colton CK. Implantable bioartificial organs. Cell Transplant 1995;4:415-436.
Carrier R, Rupnick M, Langer R, Schoen FJ, Freed L, Vunjak-Novakovic G. Perfusion improves tissue architecture of engineered cardiac muscle. Tissue Eng 2002;8:175-88.
Kada K, Yasui K, Naruse K, Kamiya K, Kodama I, Toyama J. Orientation change of cardiocytes induced by cyclic stretch stimulation: Time dependency and involvement of protein kinases. J Mol Cell Cardiol 1999;31:247-259.
Ruwhof C, van Wamel AET, Egas JM, van der Laarse A. Cyclic stretch induces the release of growth promoting factors from cultured neonatal cardiomyocytes and cardiac fibroblasts. Mol Cell Biochem 2000;208:89-98.
Zimmermann W-H, Schneiderbanger K, Schubert P, Didie M, Munzel F, Heubach JF, Kostin S, Neuhuber WL, Eshenhagen T. Tissue engineering of a differentiated cardiac muscle construct. Circ Res 2002;90:223-230.
Eschenhagen T, Didie M, Heubach J, Ravens U, Zimmermann W-H. Cardiac tissue engineering. Transplant Immunol 2002;9:315-321.
Akhyari P, Fedak WM, Weisel RD, Lee T-YJ, Verma S, Mickle AG, Li R-KL. Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts. Circulation 2002;106(Suppl I):I137-I142.
Philpott DE, Fine A, Kato K, Egnor R, Cheng L, Mednieks M. Microgravity changes in heart structure and cyclic-AMP metabolism. Physiologist 1985;28(Suppl):S209- S210.
Philpott DE, Popova IA, Kato K, Stevenson J, Miquel J, Sapp W. Morphological and biochemical examination of Cosmos 1887 rat heart tissue: Part I-Ultrastructure. FASEB 1990;4:73-78.
Thomason DB, Morrison PR, Oganov V. Altered actin and myosin expression in muscle during exposure to microgravity. J Appl Phys 1992;73:905-935.
Hoerstrup SP, Sodian R, Sperling JS, Vacanti JP, Mayer JE. New pulsatile bioreactor for in vitro formation of tissue engineered heart valves. Tissue Eng 2000;6:75- 79.
Sodian R, Lemke T, Loebe M, Hoerstrup SP, Potapov EV, Hausmann H, Meyer R, Hetzer R. New pulsatile bioreactor for fabrication of tissue-engineered patches. J Biomed Mater Res 2001;58:401-405.
Dumont K, Yperman J, Verbeken E, Segers P, Meuris B, Vandenberghe S, Flameng W, Verdonck PR. Design of a new pulsatile bioreactor for tissue engineered aortic heart valve formation. Artif Org 2002;26:710-714.
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Shachar, M., Cohen, S. Cardiac Tissue Engineering, Ex-Vivo: Design Principles in Biomaterials and Bioreactors. Heart Fail Rev 8, 271–276 (2003). https://doi.org/10.1023/A:1024729919743
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DOI: https://doi.org/10.1023/A:1024729919743