Abstract
Cardiac tissue engineering is currently being pursued with three different applications in mind: drug safety screening, disease modeling, and cardiac repair. Mini- and microengineered heart tissues are well suitable for drug safety screening and disease modeling. But generation of large cardiac patches of clinically relevant thickness, to functionally support the injured heart after myocardial infarction, still needs improvement. The high oxygen and nutrient demand request prevascularization of the engineered tissues in vitro prior to implantation. Vascularization and cardiac tissue development are influenced by several factors such as perfusion velocity, shear stress, coculture, extracellular matrix, mechanical strain, electrical stimulation, and many more. As engineering approaches get ever more sophisticated and bioreactors increasingly complex, cardiac tissue engineering evolves and quality control becomes more prominent. This chapter will focus on different perfusion bioreactors that aim at cultivating highly vascularized and functional engineered heart tissues by, e.g., direct perfusion through the tissue or cultivation on top of an engineered vascular bed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Adair TH, Gay WJ, Montani JP (1990) Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 259:R393–R404
Akhyari P, Fedak PW, Weisel RD et al (2002) Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts. Circulation 106(12 Suppl 1):I137–I142
Baiguera S, Ribatti D (2013) Endothelialization approaches for viable engineered tissues. Angiogenesis 16:1–14
Brown MA, Iyer RK, Radisic M (2008) Pulsatile perfusion bioreactor for cardiac tissue engineering. Biotechnol Prog 24:907–920
Carrier RL, Rupnick M, Langer R et al (2002) Perfusion improves tissue architecture of engineered cardiac muscle. Tissue Eng 8:175–188
Cheng M, Moretti M, Engelmayr GC, Freed LE (2009) Enhance the formation of tissue-engineered cardiac grafts. Tissue Eng Part A 15:645–653
Clark ER, Clark EL (1939) Microscopic observations on the growth of blood capillaries in the living mammal. Am J Anat 64:251–301. https://doi.org/10.1002/aja.1000640203
Dvir T, Levy O, Shachar M et al (2007) Activation of the ERK1/2 cascade via pulsatile interstitial fluid flow promotes cardiac tissue assembly. Tissue Eng 13:2185–2193
Eder A, Vollert I, Hansen A, Eschenhagen T (2015) Human engineered heart tissue as a model system for drug testing. Adv Drug Deliv Rev 96:124–24
Eschenhagen T, Fink C, Remmers U et al (1997) Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB J 11:683–694
Eschenhagen T, Eder A, Vollert I, Hansen A (2012) Physiological aspects of cardiac tissue engineering. Am J Physiol Heart Circ Physiol 303:H133–H143
Fink C, Ergün S, Kralisch D et al (2000) Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB J 14:669–679
Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288:551–556
Folkman J, Hochberg M (1973) Self-regulation of growth in three dimensions. J Exp Med 138:745–753
Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23
Godier-Furnemont AF, Tiburcy M, Wagner E et al (2015) Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation. Biomaterials 60:82–91
Hansen A, Eder A, Bönstrup M et al (2010) Development of a drug screening platform based on engineered heart tissue. Circ Res 107:35–44
Heher P, Maleiner B, Prüller J et al (2015) Acta Biomaterialia a novel bioreactor for the generation of highly aligned 3D skeletal muscle-like constructs through orientation of fibrin via application of static strain. Acta Biomater 24:251–65
Hirt MN, Hansen A, Eschenhagen T (2013) Cardiac tissue engineering – state of the art. Circ Res 114:354–367
Hirt MN, Boeddinghaus J, Mitchell A et al (2014) Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J Mol Cell Cardiol 74C:151–161
Huyer LD, Montgomery M, Zhao Y et al (2015) Biomaterial based cardiac tissue engineering and its applications. Biomed Mater 10:034004
Joung IS, Iwamoto MN, Shiu Y-T, Quam CT (2006) Cyclic strain modulates tubulogenesis of endothelial cells in a 3D tissue culture model. Microvasc Res 71:1–11
Jugdutt BI (2003) Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation 108:1395–1403
Kang T-Y, Hong JM, Kim BJ et al (2013) Enhanced endothelialization for developing artificial vascular networks with a natural vessel mimicking the luminal surface in scaffolds. Acta Biomater 9:4716–4725
Kensah G, Gruh I et al (2011) A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue. Lab Anim Care 17:463–473
Kofidis T, Lenz A, Boublik J et al (2003) Pulsatile perfusion and cardiomyocyte viability in a solid three-dimensional matrix. Biomaterials 24:5009–5014
Lesman A, Habib M, Caspi O et al (2010) Transplantation of a tissue-engineered human vascularized cardiac muscle. Tissue Eng Part A 16:115–125
Maidhof R, Marsano A, Lee EJ et al (2010) Perfusion seeding of channeled elastomeric scaffolds with myocytes and endothelial cells for cardiac tissue engineering. Biotechnol Prog 26(2):565–572
Maidhof R, Tandon N, Lee EJ et al (2012) Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue. J Tissue Eng Regen Med 6:e12–e23
Mannhardt I, Breckwoldt K, Letuffe-Brenière D et al (2016) Human engineered heart tissue: analysis of contractile force. Stem Cell Reports 7(1):29–42
Marsano A, Maidhof R, Luo J et al (2013) The effect of controlled expression of VEGF by transduced myoblasts in a cardiac patch on vascularization in a mouse model of myocardial infarction. Biomaterials 34(2):393–401
Morritt AN, Bortolotto SK, Dilley RJ et al (2007) Cardiac tissue engineering in an in vivo vascularized chamber. Circulation 115:353–360
Radisic M, Yang L, Boublik J et al (2004) Medium perfusion enables engineering of compact and contractile cardiac tissue. Am J Physiol Heart Circ Physiol 286:H507–H516
Radisic M, Deen W, Langer R, Vunjak-Novakovic G (2005) Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. Am J Physiol Heart Circ Physiol 288:H1278–H1289
Radisic M, Malda J, Epping E et al (2006a) Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol Bioeng 93:332–343
Radisic M, Park H, Chen F et al (2006b) Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. Tissue Eng 12:2077–2091
Radisic M, Marsano A, Maidhof R et al (2008) Cardiac tissue engineering using perfusion bioreactor systems. Nat Protoc 3(4):719–738
Rakusan K, Flanagan MF, Geva T et al (1992) Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure-overload hypertrophy. Circulation 86:38–46. https://doi.org/10.1161/01.CIR.86.1.38
Riemenschneider SB, Mattia DJ, Wendel JS et al (2016) Inosculation and perfusion of pre-vascularized tissue patches containing aligned human microvessels after myocardial infarction. Biomaterials 97:51–61
Robey TE, Saiget MK, Reinecke H et al (2008) Systems approaches to preventing transplanted cell death in cardiac repair. J Mol Cell Cardiol 45(4):567–581
Rotenberg MY, Ruvinov E, Armoza A, Cohen S (2012) A multi-shear perfusion bioreactor for investigating shear stress effects in endothelial cell constructs. Lab Chip 12:2696–2703
Sakaguchi K, Shimizu T, Horaguchi S et al (2013) In vitro engineering of vascularized tissue surrogates. Sci Rep 3:1316–1323
Sarig U, Nguyen EB-V, Wang Y et al (2015) Pushing the envelope in tissue engineering: ex vivo production of thick vascularized cardiac extracellular matrix constructs. Tissue Eng Part A 21:1507–1519
Sekine H, Shimizu T, Sakaguchi K et al (2013) In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels. Nat Commun 4:1399–1409
Shimizu T, Sekine H, Yang J et al (2006) Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularized myocardial tissues. FASEB J 20:708–710
Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845
Stevens KR, Kreutziger KL, Dupras SK et al (2009) Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci USA 106:16568–16573
Sun X, Altalhi W, Nunes SS (2016) Vascularization strategies of engineered tissues and their application in cardiac regeneration. Adv Drug Deliv Rev 96:183–194
Tee R, Morrison WA, Dusting GJ et al (2012) Transplantation of engineered cardiac muscle flaps in syngeneic rats. Tissue Eng Part A 18:1992–1999
Tocchio A, Tamplenizza M, Martello F et al (2015) Versatile fabrication of vascularizable scaffolds for large tissue engineering in bioreactor. Biomaterials 45:124–131
Tulloch NL, Muskheli V, Razumova M V et al (2011) Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109:47–59
Vollert I, Seiffert M, Bachmair J et al (2014) In vitro perfusion of engineered heart tissue through endothelialized channels. Tissue Eng Part A 20:854–863
Volz AC, Huber B, Kluger PJ (2016) Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering. Differentiation S0301-4681(15):30031–30031
Zhang M, Methot D, Poppa V et al (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strategies. J Mol Cell Cardiol 33(5):907–921
Zhang B, Montgomery M, Chamberlain MD et al (2016) Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat Mater 15(6):669–78
Zimmermann W-H, Didié M, Wasmeier GH et al (2002) Cardiac grafting of engineered heart tissue in syngenic rats. Circulation 106:I151–I157
Zimmermann W-H, Melnychenko I, Wasmeier G et al (2006) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12:452–458
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this entry
Cite this entry
Mannhardt, I., Marsano, A., Teuschl, A. (2021). Perfusion Bioreactors for Prevascularization Strategies in Cardiac Tissue Engineering. In: Holnthoner, W., Banfi, A., Kirkpatrick, J., Redl, H. (eds) Vascularization for Tissue Engineering and Regenerative Medicine. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-54586-8_14
Download citation
DOI: https://doi.org/10.1007/978-3-319-54586-8_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-54584-4
Online ISBN: 978-3-319-54586-8
eBook Packages: EngineeringReference Module Computer Science and Engineering