Engineered tissue grafts: opportunities and challenges in regenerative medicine

Focus Article

Adam W. Feinberg

Published Online: Oct 19 2011

DOI: 10.1002/wsbm.164

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract The human body has limited regenerative capacity in most of the major tissues and organs. This fact has spurred the field of regenerative medicine, promising to repair damage following traumatic injury or disease. Multiple therapeutic strategies are being explored including small molecules, gene delivery, and stem cells; however, tissue engineering remains a primary approach to achieving regeneration. Organ transplantation demonstrates that damaged tissues can be replaced, but technology to regenerate complex organs de novo is not yet available. Instead, tissue engineering can augment the body's own regenerative ability by replacing tissue sections and enhancing the regenerative cascade. As a consequence of these opportunities, it is timely to review the criteria and current status of engineered tissue grafts designed as patches to replace or regenerate damaged or diseased tissue and restore organ function. This topic will be explored starting from the biomaterials and cells incorporated into the engineered graft, the environment into which the graft is implanted and the integration of the engineered graft with the host. Common issues will be addressed that are relevant to regeneration in multiple tissue and organ systems. Specific examples will focus on engineered grafts for myocardial and corneal repair to illustrate the tissue‐specific challenges and opportunities and highlight the innovation needed as the field moves forward. WIREs Syst Biol Med 2012, 4:207–220. doi: 10.1002/wsbm.164 This article is categorized under: Developmental Biology > Stem Cell Biology and Regeneration Translational, Genomic, and Systems Medicine > Therapeutic Methods Translational, Genomic, and Systems Medicine > Translational Medicine

This WIREs title offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Schematic of the basic approach used to create an engineered tissue graft for regenerative medicine applications. Briefly, a biomaterial scaffold is seeded with cells and placed into a bioreactor to stimulate differentiation, maturation, and growth of the cells into a functional construct. Ideally, a combination of contractility, electrophysiology, gene expression, and structure are used as readouts to optimize the bioreactor design and improve tissue function. The engineered tissue graft is then implanted and undergoes integration with the host tissue, which may involve vascularization and innervation depending on the tissue/organ type. Alternatively, the biomaterial scaffold may be implanted as an acellular construct and recruit endogenous cells in vivo. Example applications of the engineered tissue graft include cardiac, skeletal, ophthalmic, vascular, and neural regeneration.

[ Normal View | Magnified View ]

References

Atiyeh, BS, Costagliola, M. Cultured epithelial autograft (CEA) in burn treatment: three decades later. Burns 2007, 33:405–413.
Lemaître, G, Nissan, X, Baldeschi, C, Peschanski, M. Concise review: epidermal grafting: the case for pluripotent stem cells. Stem Cells 2011, 29:895–899.
Tulloch, NL, Muskheli, V, Razumova, MV, Korte, FS, Regnier, M, Hauch, KD, Pabon, L, Reinecke, H, Murry, CE. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 2011, 109:47–59 CIRCRESAHA.110.237206.
Godier‐Furnémont, AFG, Martens, TP, Koeckert, MS, Wan, L, Parks, J, Arai, K, Zhang, G, Hudson, B, Homma, S, Vunjak‐Novakovic, G. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proc Natl Acad Sci U S A 2011, 108:7974–7979.
Fujimoto, KL, Clause, KC, Liu, LJ, Tinney, JP, Verma, S, Wagner, WR, Keller, BB, Tobita, K. Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function. Tissue Eng A 2011, 17:585–596.
Stevens, KR, Kreutziger, KL, Dupras, SK, Korte, FS, Regnier, M, Muskheli, V, Nourse, MB, Bendixen, K, Reinecke, H, Murry, CE. Physiological function and transplantation of scaffold‐free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci U S A 2009, 106:16568–16573.
Zimmermann, WH, Melnychenko, I, Wasmeier, G, Didie, M, Naito, H, Nixdorff, U, Hess, A, Budinsky, L, Brune, K, Michaelis, B, et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 2006, 12:452–458.
Shimizu, T, Sekine, H, Isoi, Y, Yamato, M, Kikuchi, A, Okano, T. Long‐term survival and growth of pulsatile myocardial tissue grafts engineered by the layering of cardiomyocyte sheets. Tissue Eng 2006, 12:499–507.
Quint, C, Kondo, Y, Manson, RJ, Lawson, JH, Dardik, A, Niklason, LE. Decellularized tissue‐engineered blood vessel as an arterial conduit. Proc Natl Acad Sci U S A 2011, 108:9214–9219.
L`Heureux, N, Paquet, S, Labbe, R, Germain, L, Auger, FA. A completely biological tissue‐engineered human blood vessel. FASEB J 1998, 12:47–56.
Stitzel, J, Liu, J, Lee, SJ, Komura, M, Berry, J, Soker, S, Lim, G, Van Dyke, M, Czerw, R, Yoo, JJ, et al. Controlled fabrication of a biological vascular substitute. Biomaterials 2006, 27:1088–1094.
Hashi, CK, Zhu, Y, Yang, G‐Y, Young, WL, Hsiao, BS, Wang, K, Chu, B, Li, S. Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts. Proc Natl Acad Sci U S A 2007, 104:11915–11920.
Kim, S‐S, Sun Park, M, Jeon, O, Yong Choi, C, Kim, B‐S. Poly(lactide‐co‐glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. Biomaterials 2006, 27:1399–1409.
Stevens, MM, Marini, RP, Schaefer, D, Aronson, J, Langer, R, Shastri, VP. In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci U S A of the United States of America 2005, 102:11450–11455.
Schek, RM, Taboas, JM, Segvich, SJ, Hollister, SJ, Krebsbach, PH. Engineered osteochondral grafts using biphasic composite solid free‐form fabricated scaffolds. Tissue Eng 2004, 10:1376–1385.
Patist, CM, Mulder, MB, Gautier, SE, Maquet, V, Jérôme, R, Oudega, M. Freeze‐dried poly(d,l‐lactic acid) macroporous guidance scaffolds impregnated with brain‐derived neurotrophic factor in the transected adult rat thoracic spinal cord. Biomaterials 2004, 25:1569–1582.
Novikova, LN, Pettersson, J, Brohlin, M, Wiberg, M, Novikov, LN. Biodegradable poly‐[beta]‐hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair. Biomaterials 2008, 29:1198–1206.
Valentin, JE, Turner, NJ, Gilbert, TW, Badylak, SF. Functional skeletal muscle formation with a biologic scaffold. Biomaterials 2010, 31:7475–7484.
Dubois, G, Segers, VFM, Bellamy, V, Sabbah, L, Peyrard, S, Bruneval, P, Hagège, AA, Lee, RT, Menasché, P. Self‐assembling peptide nanofibers and skeletal myoblast transplantation in infarcted myocardium. J Biomed Mater Res B Appl Biomater 2008, 87B: 222–228.
Takahashi, K, Tanabe, K, Ohnuki, M, Narita, M, Ichisaka, T, Tomoda, K, Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131:861–872.
Burridge, PW, Thompson, S, Millrod, MA, Weinberg, S, Yuan, X, Peters, A, Mahairaki, V, Koliatsos, VE, Tung, L, Zambidis, ET. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PLoS ONE 2011, 6:e18293.
Kattman, SJ, Witty, AD, Gagliardi, M, Dubois, NC, Niapour, M, Hotta, A, Ellis, J, Keller, G. Stage‐specific optimization of activin/nodal and bmp signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 2011, 8:228–240.
Terrovitis, JV, Smith, RR, Marban, E. Assessment and optimization of cell engraftment after transplantation into the heart. Circ Res 2010, 106:479–494.
Passier, R, van Laake, LW, Mummery, CL. Stem‐cell‐based therapy and lessons from the heart. Nature 2008, 453:322–329.
Giordano, A, Galderisi, U, Marino, IR. From the laboratory bench to the patient`s bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 2007, 211:27–35.
McKee, CT, Last, JA, Russell, P, Murphy, CJ. Indentation versus tensile measurements of Young`s modulus for soft biological tissues. Tissue Eng B Rev 2011, 17:155–164.
Engler, AJ, Sen, S, Sweeney, HL, Discher, DE. Matrix elasticity directs stem cell lineage specification. Cell 2006, 126:677–689.
Ballyk, PD, Walsh, C, Butany, J, Ojha, M. Compliance mismatch may promote graft‐artery intimal hyperplasia by altering suture‐line stresses. J Biomech 1998, 31:229–237.
Kannan, RY, Salacinski, HJ, Butler, PE, Hamilton, G, Seifalian, AM. Current status of prosthetic bypass grafts: a review. J Biomed Mater Res B Appl Biomater 2005, 74B:570–581.
Jain, RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide‐co‐glycolide) (PLGA) devices. Biomaterials 2000, 21:2475–2490.
Bettinger, CJ. Biodegradable elastomers for tissue engineering and cell–biomaterial interactions. Macromol Biosci 2011, 11:467–482.
Feinberg, AW, Parker, KK. Surface‐initiated assembly of protein nanofabrics. Nano Lett 2010, 10:2184–2191.
Hutmacher, DW. Scaffold design and fabrication technologies for engineering tissues—state of the art and future perspectives. J Biomater Sci Polym Ed 2001, 12:107–124.
Madurantakam, PA, Cost, CP, Simpson, DG, Bowlin, GL. Science of nanofibrous scaffold fabrication: strategies for next generation tissue‐engineering scaffolds. Nanomedicine 2009, 4:193–206.
Wheeldon, I, Farhadi, A, Bick, AG, Jabbari, E, Khademhosseini, A. Nanoscale tissue engineering: spatial control over cell‐materials interactions. Nanotechnology 2011, 22:1–16.
Mustonen, RK, McDonald, MB, Srivannaboon, S, Tan, AL, Doubrava, MW, Kim, CK. Normal human corneal cell populations evaluated by in vivo scanning slit confocal microscopy. Cornea 1998, 17:485–492.
Tang, Y, Nyengaard, JR, Andersen, JB, Baandrup, U, Gundersen, HJG. The application of stereological methods for estimating structural parameters in the human heart. Anat Rec (Hoboken) 2009, 292:1630–1647.
Domian, IJ, Chiravuri, M, van der Meer, P, Feinberg, AW, Shi, X, Shao, Y, Wu, SM, Parker, KK, Chien, KR. Generation of functional ventricular heart muscle from mouse ventricular progenitor cells. Science 2009, 326:426–429.
Dimos, JT, Rodolfa, KT, Niakan, KK, Weisenthal, LM, Mitsumoto, H, Chung, W, Croft, GF, Saphier, G, Leibel, R, Goland, R, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008, 321: 1218–1221.
Phinney, DG, Prockop, DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair—current views. Stem Cells 2007, 25:2896–2902.
Gepstein, L. Derivation and potential applications of human embryonic stem cells. Circ Res 2002, 91:866–876.
Kiskinis, E, Eggan, K. Progress toward the clinical application of patient‐specific pluripotent stem cells. J Clin Invest 2010, 120:51–59.
Yoshida, Y, Yamanaka, S. iPS cells: a source of cardiac regeneration. J Mol Cell Cardiol 2011, 50:327–332.
Gilbert, TW, Sellaro, TL, Badylak, SF. Decellularization of tissues and organs. Biomaterials 2006, 27:3675–3683.
Pörtner, R, Nagel‐Heyer, S, Goepfert, C, Adamietz, P, Meenen, NM. Bioreactor design for tissue engineering. J Biosci Bioeng 2005, 100:235–245.
Lee, K‐W, Stolz, DB, Wang, Y. Substantial expression of mature elastin in arterial constructs. Proc Natl Acad Sci U S A 2011, 108:2705–2710.
McCoy, RJ, O`Brien, FJ. Influence of shear stress in perfusion bioreactor cultures for the development of three‐dimensional bone tissue constructs: a review. Tissue Eng B Rev 2010, 16:587–601.
Concaro, S, Gustavson, F, Gatenholm, P. Bioreactors for tissue engineering of cartilage. [Without Title]. Heidelberg: Springer; 2011, 1–19.
Elder, BD, Athanasiou, KA. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. Tissue Eng B Rev 2009, 15:43–53.
Barron, V, Lyons, E, Stenson‐Cox, C, McHugh, PE, Pandit, A. Bioreactors for cardiovascular cell and tissue growth: a review. Ann Biomed Eng 2003, 31:1017–1030.
Powell, CA, Smiley, BL, Mills, J, Vandenburgh, HH. Mechanical stimulation improves tissue‐engineered human skeletal muscle. Am J Physiol Cell Physiol 2002, 283:C1557–C1565.
Radisic, M, Park, H, Gerecht, S, Cannizzaro, C, Langer, R, Vunjak‐Novakovic, G. Biomimetic approach to cardiac tissue engineering. Philos Trans R Soc B Biol Sci 2007, 362:1357–1368.
Allen, JW, Bhatia, SN. Formation of steady‐state oxygen gradients in vitro: application to liver zonation. Biotechnol Bioeng 2003, 82:253–262.
Burdick, JA, Vunjak‐Novakovic, G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng A 2009, 15:205–219.
Kannan, RY, Salacinski, HJ, Sales, K, Butler, P, Seifalian, AM. The roles of tissue engineering and vascularisation in the development of micro‐vascular networks: a review. Biomaterials 2005, 26:1857–1875.
Birla, RK, Borschel, GH, Dennis, RG. In vivo conditioning of tissue‐engineered heart muscle improves contractile performance. Artif Organs 2005, 29:866–875.
Keel, M, Trentz, O. Pathophysiology of polytrauma. Injury 2005, 36:691–709.
DePalma, RG, Burris, DG, Champion, HR, Hodgson, MJ. Blast injuries. New Engl J Med 2005, 352:1335–1342.
Pollak, AN, Ficke, CJR. Extremity war injuries: challenges in definitive reconstruction. J Am Acad Orthop Surg 2008, 16:628–634.
Murray, CK, Wilkins, K, Molter, NC, Yun, HC, Dubick, MA, Spott, MA, Jenkins, D, Eastridge, B, Holcomb, JB, Blackbourne, LH, et al. Infections in combat casualties during operations Iraqi and enduring freedom. J Trauma 2009, 66:S138–S144.
Hawksworth, JS, Stojadinovic, A, Gage, FA, Tadaki, DK, Perdue, PW, Forsberg, J, Davis, TA, Dunne, JR, Denobile, JW, Brown, TS, et al. Inflammatory biomarkers in combat wound healing. Ann Surg 2009, 250:1002–1007.
Phelps, EA, García, AJ. Engineering more than a cell: vascularization strategies in tissue engineering. Curr Opin Biotechnol 2010, 21:704–709.
Chalfoun, CT, Wirth, GA, Evans, GRD. Tissue engineered nerve constructs:where do we stand? J Cell Mol Med 2006, 10:309–317.
Caissie, R, Gingras, M, Champigny, M‐F, Berthod, F. In vivo enhancement of sensory perception recovery in a tissue‐engineered skin enriched with laminin. Biomaterials 2006, 27:2988–2993.
Niederer, RL, Perumal, D, Sherwin, T, McGhee, CNJ. Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study. Invest Ophthalmol Vis Sci 2007, 48:621–626.
Kingham, PJ, Terenghi, G. Bioengineered nerve regeneration and muscle reinnervation. J Anat 2006, 209:511–526.
Stevens, MJ, Raffel, DM, Allman, KC, Dayanikli, F, Ficaro, E, Sandford, T, Wieland, DM, Pfeifer, MA, Schwaiger, M. Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation 1998, 98:961–968.
Laco, F, Grant, MH, Flint, DJ, Black, RA. Cellular trans‐differentiation and morphogenesis toward the lymphatic lineage in regenerative medicine. Stem Cells Dev 2011, 20:181–195.
Lynn, AK, Yannas, IV, Bonfield, W. Antigenicity and immunogenicity of collagen. J Biomed Mater Res B Appl Biomater 2004, 71B:343–354.
Anderson, JM, Rodriguez, A, Chang, DT. Foreign body reaction to biomaterials. Semin Immunol 2008, 20:86–100.
Chan, G, Mooney, DJ. New materials for tissue engineering: towards greater control over the biological response. Trends Biotechnol 2008, 26:382–392.
Holman, ER, Buller, VGM, de Roos, A, van der Geest, RJ, Baur, LHB, van der Laarse, A, Bruschke, AVG, Reiber, JHC, van der Wall, EE. Detection and quantification of dysfunctional myocardium by magnetic resonance imaging: a new three‐dimensional method for quantitative wall‐thickening analysis. Circulation 1997, 95:924–931.
Jonas, JB, Holbach, L. Central corneal thickness and thickness of the lamina cribrosa in human eyes. Invest Ophthalmol Vis Sci 2005, 46:1275–1279.
You, L, Kruse, FE, Völcker, HE. Neurotrophic factors in the human cornea. Invest Ophthalmol Vis Sci 2000, 41:692–702.
Niederkorn, JY. Immune privilege and immune regulation in the eye. Adv Immunol 1990, 48:191–226.
Ott, HC, Matthiesen, TS, Goh, S‐K, Black, LD, Kren, SM, Netoff, TI, Taylor, DA. Perfusion‐decellularized matrix: using nature`s platform to engineer a bioartificial heart. Nat Med 2008, 14:213–221.
Wainwright, JM, Czajka, CA, Patel, UB, Freytes, DO, Tobita, K, Gilbert, TW, Badylak, SF. Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng C Methods 2010, 16:525–532.
Boublik, J, Park, H, Radisic, M, Tognana, E, Chen, F, Pei, M, Vunjak‐Novakovic, G, Freed, LE. Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric. Tissue Eng 2005, 11:1122–1132.
Black, LD, Meyers, JD, Weinbaum, JS, Shvelidze, YA, Tranquillo, RT. Cell‐induced alignment augments twitch force in fibrin gel‐based engineered myocardium via gap junction modification. Tissue Eng A 2009, 15:3099–3108.
Matsuura, K, Masuda, S, Haraguchi, Y, Yasuda, N, Shimizu, T, Hagiwara, N, Zandstra, PW, Okano, T. Creation of mouse embryonic stem cell‐derived cardiac cell sheets. Biomaterials 2011, 32:7355–7362.
Shimizu, T, Yamato, M, Kikuchi, A, Okano, T. Cell sheet engineering for myocardial tissue reconstruction. Biomaterials 2003, 24:2309–2316.
Bursac, N, Loo, Y, Leong, K, Tung, L. Novel anisotropic engineered cardiac tissues: studies of electrical propagation. Biochem Biophys Res Commun 2007, 361:847–853.
Lesman, A, Habib, M, Caspi, O, Gepstein, A, Arbel, G, Levenberg, S, Gepstein, L. Transplantation of a tissue‐engineered human vascularized cardiac muscle. Tissue Eng A 16:115–125.
Engelmayr, GC, Cheng, M, Bettinger, CJ, Borenstein, JT, Langer, R, Freed, LE. Accordion‐like honeycombs for tissue engineering of cardiac anisotropy. Nat Mater 2008, 7:1003–1010.
Madden, LR, Mortisen, DJ, Sussman, EM, Dupras, SK, Fugate, JA, Cuy, JL, Hauch, KD, Laflamme, MA, Murry, CE, Ratner, BD. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc Natl Acad Sci U S A 2010, 107:15211–15216.
Zong, X, Bien, H, Chung, C‐Y, Yin, L, Fang, D, Hsiao, BS, Chu, B, Entcheva, E. Electrospun fine‐textured scaffolds for heart tissue constructs. Biomaterials 2005, 26:5330–5338.
Fagerholm, P, Lagali, NS, Merrett, K, Jackson, WB, Munger, R, Liu, Y, Polarek, JW, Söderqvist, M, Griffith, M. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24‐month follow‐up of a phase 1 clinical study. Sci Transl Med 2010, 2:46ra61.
Choi, JS, Williams, JK, Greven, M, Walter, KA, Laber, PW, Khang, G, Soker, S. Bioengineering endothelialized neo‐corneas using donor‐derived corneal endothelial cells and decellularized corneal stroma. Biomaterials 2010, 31:6738–6745.
Hsiue, GH, Lai, JY, Chen, KH, Hsu, WM. A novel strategy for corneal endothelial reconstruction with a bioengineered cell sheet. Transplantation 2006, 81:473–476.
Nishida, K, Yamato, M, Hayashida, Y, Watanabe, K, Maeda, N, Watanabe, H, Yamamoto, K, Nagai, S, Kikuchi, A, Tano, Y, et al. Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature‐responsive cell culture surface. Transplantation 77:379–385.
Li, F, Carlsson, D, Lohmann, C, Suuronen, E, Vascotto, S, Kobuch, K, Sheardown, H, Munger, R, Nakamura, M, Griffith, M. Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation. Proc Natl Acad Sci U S A 2003, 100:15346–15351.
American Heart Association. Heart Disease and Stroke Statistics—2010 Update. Dallas, TX: American Heart Association; 2010.
Roger, VL, Go, AS, Lloyd‐Jones, DM, Adams, RJ, Berry, JD, Brown, TM, Carnethon, MR, Dai, S, de Simone, G, Ford, ES, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 2011, 123:e18–e209.
Pasumarthi, KBS, Field, LJ. Cardiomyocyte cell cycle regulation. Circ Res 2002, 90:1044–1054.
Bergmann, O, Bhardwaj, RD, Bernard, S, Zdunek, S, Barnabe‐Heider, F, Walsh, S, Zupicich, J, Alkass, K, Buchholz, BA, Druid, H, et al. Evidence for Cardiomyocyte Renewal in Humans. Science 2009, 324:98–102.
Caspi, O, Lesman, A, Basevitch, Y, Gepstein, A, Arbel, G, Habib, IHM, Gepstein, L, Levenberg, S. Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res 2007, 100:263–272.
Anderson, D, Self, T, Mellor, IR, Goh, G, Hill, SJ, Denning, C. Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Mol Ther 2007, 15:2027–2036.
Kehat, I, Khimovich, L, Caspi, O, Gepstein, A, Shofti, R, Arbel, G, Huber, I, Satin, J, Itskovitz‐Eldor, J, Gepstein, L. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotech 2004, 22:1282–1289.
Zimmermann, W‐H. Embryonic and embryonic‐like stem cells in heart muscle engineering. J Mol Cell Cardiol 2011, 50:320–326.
Zhang, J, Wilson, GF, Soerens, AG, Koonce, CH, Yu, J, Palecek, SP, Thomson, JA, Kamp, TJ. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 2009, 104:e30–e41.
Gai, H, Leung, ELH, Costantino, PD, Aguila, JR, Nguyen, DM, Fink, LM, Ward, DC, Ma, YP. Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts. Cell Biol Int 2009, 33:1184–1193.
Chien, KR, Domian, IJ, Parker, KK. Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science 2008, 322:1494–1497.
Sturzu, AC, Wu, SM. Developmental and regenerative biology of multipotent cardiovascular progenitor cells. Circ Res 2011, 108:353–364.
Martinez, EC, Kofidis, T. Adult stem cells for cardiac tissue engineering. J Mol Cell Cardiol 2011, 50:312–319.
Efe, JA, Hilcove, S, Kim, J, Zhou, H, Ouyang, K, Wang, G, Chen, J, Ding, S. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol (Epub ahead of print).
Ieda, M, Fu, J‐D, Delgado‐Olguin, P, Vedantham, V, Hayashi, Y, Bruneau, BG, Srivastava, D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010, 142:375–386.
He, J‐Q, Ma, Y, Lee, Y, Thomson, JA, Kamp, TJ. Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 2003, 93:32–39.
Ng, SY, Wong, CK, Tsang, SY. Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell‐derived cardiomyocytes for future therapies. Am J Physiol Cell Physiol 2010, 299:C1234–C1249.
Bollini, S, Smart, N, Riley, PR. Resident cardiac progenitor cells: at the heart of regeneration. J Mol Cell Cardiol 2011, 50:296–303.
Sartiani, L, Bettiol, E, Stillitano, F, Mugelli, A, Cerbai, E, Jaconi, ME. Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach. Stem Cells 2007, 25:1136–1144.
Itzhaki, I, Rapoport, S, Huber, I, Mizrahi, I, Zwi‐Dantsis, L, Arbel, G, Schiller, J, Gepstein, L. Calcium handling in human induced pluripotent stem cell derived cardiomyocytes. PLoS ONE 2011, 6:e18037.
Xi, J, Khalil, M, Shishechian, N, Hannes, T, Pfannkuche, K, Liang, H, Fatima, A, Haustein, M, Suhr, F, Bloch, W, et al. Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells. FASEB J 2010, 24:2739–2751.
Porrello, ER, Mahmoud, AI, Simpson, E, Hill, JA, Richardson, JA, Olson, EN, Sadek, HA. Transient regenerative potential of the neonatal mouse heart. Science 2011, 331:1078–1080.
Nishimura, S, Yasuda, S, Katoh, M, Yamada, KP, Yamashita, H, Saeki, Y, Sunagawa, K, Nagai, R, Hisada, T, Sugiura, S. Single cell mechanics of rat cardiomyocytes under isometric, unloaded, and physiologically loaded conditions. Am J Physiol Heart Circ Physiol 2004, 287:H196–H202.
Brady, AJ, Tan, ST, Ricchiuti, NV. Contractile force measured in unskinned isolated adult rat heart fibres. Nature 1979, 282:728.
Berry, MF, Engler, AJ, Woo, YJ, Pirolli, TJ, Bish, LT, Jayasankar, V, Morine, KJ, Gardner, TJ, Discher, DE, Sweeney, HL. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol 2006, 290:H2196–H2203.
Jacot, JG, McCulloch, AD, Omens, JH. Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. Biophys J 2008, 95:3479–3487.
Engler, AJ, Carag‐Krieger, C, Johnson, CP, Raab, M, Tang, H‐Y, Speicher, DW, Sanger, JW, Sanger, JM, Discher, DE. Embryonic cardiomyocytes beat best on a matrix with heart‐like elasticity: scar‐like rigidity inhibits beating. J Cell Sci 2008, 121:3794–3802.
Stoker, ME, Gerdes, AM, May, JF. Regional differences in capillary density and myocyte size in the normal human heart. Anat Rec 1982, 202:187–191.
Alford, PW, Feinberg, AW, Sheehy, SP, Parker, KK. Biohybrid thin films for measuring contractility in engineered cardiovascular muscle. Biomaterials 2010, 31:3613–3621.
Chang, MG, Zhang, Y, Chang, CY, Xu, L, Emokpae, R, Tung, L, Marban, E, Abraham, MR. Spiral waves and reentry dynamics in an in vitro model of the healed infarct border zone. Circ Res 2009, 105:1062–1071.
Cysyk, J, Tung, L. Electric field perturbations of spiral waves attached to millimeter‐size obstacles. Biophys J 2008, 94:1533–1541.
Fast, VG, Darrow, BJ, Saffitz, JE, Kleber, AG. Anisotropic activation spread in heart cell monolayers assessed by high‐resolution optical mapping: role of tissue discontinuities. Circ Res 1996, 79:115–127.
Zong, XH, Bien, H, Chung, CY, Yin, LH, Fang, DF, Hsiao, BS, Chu, B, Entcheva, E. Electrospun fine‐textured scaffolds for heart tissue constructs. Biomaterials 2005, 26:5330–5338.
Feinberg, AW, Feigel, A, Shevkoplyas, SS, Sheehy, S, Whitesides, GM, Parker, KK. Muscular thin films for building actuators and powering devices. Science 2007, 317:1366–1370.
Masuda, S, Shimizu, T, Yamato, M, Okano, T. Cell sheet engineering for heart tissue repair. Adv Drug Deliv Rev 2008, 60:277–285.
Bers, DM. Cardiac excitation‐contraction coupling. Nature 2002, 415:198–205.
Roell, W, Lewalter, T, Sasse, P, Tallini, YN, Choi, B‐R, Breitbach, M, Doran, R, Becher, UM, Hwang, S‐M, Bostani, T, et al. Engraftment of connexin 43‐expressing cells prevents post‐infarct arrhythmia. Nature 2007, 450:819–824.
Lesman, A, Gepstein, L, Levenberg, S. Vascularization shaping the heart. Ann N Y Acad Sci 2010, 1188: 46–51.
Piatigorsky, J. Enigma of the abundant water‐soluble cytoplasmic proteins of the cornea—the “refracton” hypothesis. Cornea 2001, 20:853–858.
Resnikoff, S, Pascolini, D, Etya`ale, D, Kocur, I, Pararajasegaram, R, Pokharel, G, Mariotti, SP. Global data on visual impairment in the year 2002. Bull World Health Organ 2004, 82:844–851.
Nishida, T. Fundamentals of cornea and external disease. In: Krachmer, JJ, Mannis, MJ, Holland, EJ, eds. Cornea. St. Louis, MO: Mosby‐Year Book Inc.; 1997.
McLaughlin, CR, Tsai, RJF, Latorre, MA, Griffith, M. Bioengineered corneas for transplantation and in vitro toxicology. Front Biosci 2009, 14:3326–3337.
Peh, GSL, Beuerman, RW, Colman, A, Tan, DT, Mehta, JS. Human corneal endothelial cell expansion for corneal endothelium transplantation: an overview. Transplantation 2011, 91:811–819.
Daniels, JT, Dart, JKG, Tuft, SJ, Khaw, PT. Corneal stem cells in review. Wound Repair Regen 2001, 9:483–494.
Komai, Y, Ushiki, T. The three‐dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci 1991, 32: 2244–2258.
Du, Y, Carlson, EC, Funderburgh, ML, Birk, DE, Pearlman, E, Guo, N, Kao, WWY, Funderburgh, JL. Stem cell therapy restores transparency to defective murine corneas. Stem Cells 2009, 27: 1635–1642.
Senoo, T, Joyce, NC. Cell cycle kinetics in corneal endothelium from old and young donors. Invest Ophthalmol Vis Sci 2000, 41:660–667.
Thompson, RW, Price, MO, Bowers, PJ, Price, FW. Long‐term graft survival after penetrating keratoplasty. Ophthalmology 2003, 110:1396–1402.
Melles, GRJ, Ong, TS, Ververs, B, van der Wees, J. Descemet membrane endothelial keratoplasty (DMEK). Cornea 2006, 25:987–990.
Borderie, VM, Boëlle, P‐Y, Touzeau, O, Allouch, C, Boutboul, S, Laroche, L. Predicted long‐term outcome of corneal transplantation. Ophthalmology 2009, 116:2354–2360.
Odedra, D., Chiu, L, Reis, L, Rask, F, Chiang, K, Radisic, M. Cardiac tissue engineering. “A Review of the Past and Future Trends” In: Burdick, JA, Mauck, RL, eds. Biomaterials for Tissue Engineering Applications: A Review of the Past and Future Trends. Vienna: Springer; 2011, 421–456.
Vunjak‐Novakovic, G, Tandon, N, Godier, A, Maidhof, R, Marsano, A, Martens, TP, Radisic, M. Challenges in cardiac tissue engineering. Tissue Eng B Rev 2010, 16:169–187.
Pok, S., Jacot, J. Biomaterials advances in patches for congenital heart defect repair. J Cardiovasc Transl Res:1–9 2011, 4:646–654.
Engelmann, K, Bednarz, J, Valtink, M. Prospects for endothelial transplantation. Exp Eye Res 2004, 78:573–578.
Dambrot, C, Passier, R, Atsma, D, Mummery, CL. Cardiomyocyte differentiation of pluripotent stem cells and their use as cardiac disease models. Biochem J 2011, 434:25–35.
McAllister, TN, Maruszewski, M, Garrido, SA, Wystrychowski, W, Dusserre, N, Marini, A, Zagalski, K, Fiorillo, A, Avila, H, Manglano, X, et al. Effectiveness of haemodialysis access with an autologous tissue‐engineered vascular graft: a multicentre cohort study. Lancet 2009, 373:1440–1446.
Shin`oka, T, Matsumura, G, Hibino, N, Naito, Y, Watanabe, M, Konuma, T, Sakamoto, T, Nagatsu, M, Kurosawa, H. Midterm clinical result of tissue‐engineered vascular autografts seeded with autologous bone marrow cells. J Thorac Cardiovasc Surg 2005, 129:1330–1338.
Dahl, SLM, Kypson, AP, Lawson, JH, Blum, JL, Strader, JT, Li, Y, Manson, RJ, Tente, WE, DiBernardo, L, Hensley, MT, et al. Readily Available Tissue‐Engineered Vascular Grafts. Sci Transl Med 2011, 3:68ra69.
Sell, SA, McClure, MJ, Garg, K, Wolfe, PS, Bowlin, GL. Electrospinning of collagen/biopolymers for regenerative medicine and cardiovascular tissue engineering. Adv Drug Deliv Rev 2009, 61:1007–1019.
Stankus, JJ, Guan, JJ, Wagner, WR. Fabrication of biodegradable elastomeric scaffolds with sub‐micron morphologies. J Biomed Mater Res A 2004, 70A:603–614.

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

Engineered tissue grafts: opportunities and challenges in regenerative medicine

Related Articles

Browse by Topic

Access to this WIREs title is by subscription only.

The latest WIREs articles in your inbox