Skip to main content Accessibility help

Tissue engineering toward organ-specific regeneration and disease modeling

  • Christian Mandrycky (a1), Kiet Phong (a1) and Ying Zheng (a1)


Tissue engineering has been recognized as a translational approach to replace damaged tissue or whole organs. Engineering tissue, however, faces an outstanding knowledge gap in the challenge to fully recapitulate complex organ-specific features. Major components, such as cells, matrix, and architecture, must each be carefully controlled to engineer tissue-specific structure and function that mimics what is found in vivo. Here we review different methods to engineer tissue, and discuss critical challenges in recapitulating the unique features and functional units in four major organs—the kidney, liver, heart, and lung, which are also the top four candidates for organ transplantation in the USA. We highlight advances in tissue engineering approaches to enable the regeneration of complex tissue and organ substitutes, and provide tissue-specific models for drug testing and disease modeling. We discuss the current challenges and future perspectives toward engineering human tissue models.


Corresponding author

Address all correspondence to Ying Zheng at


Hide All
1.MacNeil, S.: Progress and opportunities for tissue-engineered skin. Nature 445, 874 (2007).
2.Atala, A., Bauer, S.B., Soker, S., Yoo, J.J., and Retik, A.B.: Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367, 1241 (2006).
3.Bhatia, S.N. and Ingber, D.E.: Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760 (2014).
4.Wikswo, J.P.: The relevance and potential roles of microphysiological systems in biology and medicine. Exp. Biol. Med. (Maywood) 239, 1061 (2014).
5.Weber, E.J., Chapron, A., Chapron, B.D., Voellinger, J.L., Lidberg, K.A., Yeung, C.K., Wang, Z., Yamaura, Y., Hailey, D.W., Neumann, T., Shen, D.D., Thummel, K.E., Muczynski, K.A., Himmelfarb, J., and Kelly, E.J.: Development of a microphysiological model of human kidney proximal tubule function. Kidney Int. 90, 627 (2016).
6.Fernandez, C.E., Yen, R.W., Perez, S.M., Bedell, H.W., Povsic, T.J., Reichert, W.M., and Truskey, G.A.: Human vascular microphysiological system for in vitro drug screening. Sci. Rep. 6, 21579 (2016).
7.Mathur, A., Loskill, P., Shao, K., Huebsch, N., Hong, S., Marcus, S.G., Marks, N., Mandegar, M., Conklin, B.R., Lee, L.P., and Healy, K.E.: Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 5, 8883 (2015).
8.Atala, A., Kasper, F.K., and Mikos, A.G.: Engineering complex tissues. Sci Transl. Med. 4, 160rv12 (2012).
9.Mikos, A.G., Herring, S.W., Ochareon, P., Elisseeff, J., Lu, H.H., Kandel, R., Schoen, F.J., Toner, M., Mooney, D., Atala, A., Van Dyke, M.E., Kaplan, D., and Vunjak-Novakovic, G.: Engineering complex tissues. Tissue Eng. 12, 3307 (2006).
10.Kellar, C.A.: Solid organ transplantation overview and delection criteria. Am. J. Manag. Care 21, S4 (2015).
11.Magee, J.C., Barr, M.L., Basadonna, G.P., Johnson, M.R., Mahadevan, S., McBride, M.A., Schaubel, D.E., and Leichtman, A.B.: Repeat organ transplantation in the United States, 1996–2005. Am. J. Transplant. 7, 1424 (2007).
12.Pocock, G., Richards, C.D., and Richards, D.A.: Human Physiology (Oxford University Press, 2013).
13.Jen, K.-Y., Haragsim, L., and Laszik, Z.G.: Kidney microvasculature in health and disease. Exp. Model. Ren. Dis. Pathog. Diagn. 169, 51 (2011).
14.Basile, D.P.: The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int. 72, 151 (2007).
15.Basile, D.P., Friedrich, J.L., Spahic, J., Knipe, N., Mang, H., Leonard, E.C., Changizi-Ashtiyani, S., Bacallao, R.L., Molitoris, B.A., and Sutton, T.A.: Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury. Am. J. Physiol. Physiol. 300, F721 (2011).
16.Basile, D.P.: Rarefaction of peritubular capillaries following ischemic acute renal failure: a potential factor predisposing to progressive nephropathy. Curr. Opin. Nephrol. Hypertens. 13, 1 (2004).
17.Chawla, L.S., Eggers, P.W., Star, R.A., and Kimmel, P.L.: Acute kidney injury and chronic kidney disease as interconnected syndromes. N. Engl. J. Med. 371, 58 (2014).
18.Bussolati, B. and Camussi, G.: Therapeutic use of human renal progenitor cells for kidney regeneration. Nat. Rev. Nephrol. 11, 695 (2015).
19.Gordillo, M., Evans, T., and Gouon-Evans, V.: Orchestrating liver development. Development 142, 2094 (2015).
20.Laizzo, P.A.: Handbook of Cardiac Anatomy, Physiology, and Devices (Springer International Publishing, 2009).
21.Desai, T.J., Brownfield, D.G., and Krasnow, M.A.: Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507, 190 (2014).
22.Bulger, R.E. and Dobyan, D.C.: Recent structure-function relationships in normal and injured mammalian kidneys. Anat. Rec. 205, 1 (1983).
23.Furriols, M., Chillarón, J., Mora, C., Castelló, A., Bertran, J., Camps, M., Testar, X., Vilaró, S., Zorzano, A., and Palacín, M.: rBAT, related to L-cysteine transport, is localized to the microvilli of proximal straight tubules, and its expression is regulated in kidney by development. J. Biol. Chem. 268, 27060 (1993).
24.Greka, A. and Mundel, P.: Cell biology and pathology of podocytes. Annu. Rev. Physiol. 74, 299 (2012).
25.Pavenstädt, H.: Roles of the podocyte in glomerular function. Am. J. Physiol. Renal Physiol. 278, F173 (2000).
26.Salmon, A.H.J., Neal, C.R., and Harper, S.J.: New aspects of glomerular filtration barrier structure and function: five layers (at least) not three. Curr. Opin. Nephrol. Hypertens. 18, 197 (2009).
27.Shirato, I., Tomino, Y., Koide, H., and Sakai, T.: Fine structure of the glomerular basement membrane of the rat kidney visualized by high-resolution scanning electron microscopy. Cell Tissue Res. 266, 1 (1991).
28.Cortes, P., Méndez, M., Riser, B.L., Guérin, C.J., Rodríguez-Barbero, A., Hassett, C., and Yee, J.: F-actin fiber distribution in glomerular cells: structural and functional implications. Kidney Int. 58, 2452 (2000).
29.Hui, E.E. and Bhatia, S.N.: Micromechanical control of cell–cell interactions. Proc. Natl. Acad. Sci. U. S. A. 104, 5722 (2007).
30.Albrecht, D.R., Underhill, G.H., Wassermann, T.B., Sah, R.L., and Bhatia, S.N.: Probing the role of multicellular organization in three-dimensional microenvironments. Nat. Methods 3, 369 (2006).
31.Bhatia, S.N., Underhill, G.H., Zaret, K.S., and Fox, I.J.: Cell and tissue engineering for liver disease. Sci. Transl. Med. 6, 245sr2 (2014).
32.Stevens, K.R., Ungrin, M.D., Schwartz, R.E., Ng, S., Carvalho, B., Christine, K.S., Chaturvedi, R.R., Li, C.Y., Zandstra, P.W., Chen, C.S., and Bhatia, S.N.: InVERT molding for scalable control of tissue microarchitecture. Nat. Commun. 4, 1847 (2013).
33.Shan, J., Logan, D.J., Root, D.E., Carpenter, A.E., and Bhatia, S.N.: High-throughput platform for identifying molecular factors involved in phenotypic stabilization of primary human hepatocytes in vitro. J. Biomol. Screen. 21, 897 (2016).
34.Krishna, M.: Microscopic anatomy of the liver. Clin. Liver Dis. 2, S4 (2013).
35.Rappaport, A.M., Borowy, Z.J., Lougheed, W.M., and Lotto, W.N.: Subdivision of hexagonal liver lobules into a structural and functional unit. Role in hepatic physiology and pathology. Anat. Rec. 119, 11 (1954).
36.Wisse, E., Braet, F., Dianzhong Luo, D., De Zanger, R., Jans, D., Crabbe, E., and Vermoesen, A.: Structure and function of sinusoidal lining cells in the liver. Toxicol. Pathol. 24, 100 (1996).
37.Wisse, E., Braet, F., Luo, D., Vermijlen, D., Eddouks, M., Konstandoulaki, M., Empsen, C., and de Zanger, R.B.: Endothelial cells of the hepatic sinusoids: a review. In Liver Diseases and Hepatic Sinusoidal Cells, edited by Tanikawa, K. and Ueno, T. (Springer, Tokyo, Japan, 1999), pp. 1753.
38.Bilzer, M., Roggel, F., and Gerbes, A.L.: Role of Kupffer cells in host defense and liver disease. Liver Int. 26, 1175 (2006).
39.Puche, J.E., Saiman, Y., and Friedman, S.L.: Hepatic stellate cells and liver fibrosis. Compr. Physiol. 3, 1473 (2013).
40.Malarkey, D.E., Johnson, K., Ryan, L., Boorman, G., and Maronpot, R.R.: New insights into functional aspects of liver morphology. Toxicol. Pathol. 33, 27 (2005).
41.Buckberg, G., Hoffman, J.I.E., Mahajan, A., Saleh, S., and Coghlan, C.: Cardiac mechanics revisited: the relationship of cardiac architecture to ventricular function. Circulation 118, 2571 (2008).
42.Young, A.A. and Cowan, B.R.: Evaluation of left ventricular torsion by cardiovascular magnetic resonance. J. Cardiovasc. Magn. Reson. 14, 49 (2012).
43.Poveda, F., Gil, D., Martí, E., Andaluz, A., Ballester, M., and Carreras, F.: Helical structure of the cardiac ventricular anatomy assessed by diffusion tensor magnetic resonance imaging with multiresolution tractography. Rev. Española Cardiol. Engl. Ed. 66, 782 (2013).
44.Kocica, M.J., Corno, A.F., Carreras-Costa, F., Ballester-Rodes, M., Moghbel, M.C., Cueva, C.N.C., Lackovic, V., Kanjuh, V.I., and Torrent-Guasp, F.: The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium. Eur. J. Cardio-Thorac. Surg. 29, S21 (2006).
45.Korecky, B., Hai, C.M., and Rakusan, K.: Functional capillary density in normal and transplanted rat hearts. Can. J. Physiol. Pharmacol. 60, 23 (1982).
46.Cheung, D.Y., Duan, B., and Butcher, J.T.: Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions. Expert Opin. Biol. Ther. 15, 1155 (2015).
47.Schoen, F.J. and Levy, R.J.: Tissue heart valves: current challenges and future research perspectives. J. Biomed. Mater. Res. 47, 439 (1999).
48.McNulty, W. and Usmani, O.S.: Techniques of assessing small airways dysfunction. Eur. Clin. Respir. J. 1, 25898 (2014).
49.Hsia, C.C.W., Hyde, D.M., and Weibel, E.R.: Lung structure and the intrinsic challenges of gas exchange. Compr. Physiol. 6, 827 (2016).
50.Mercer, R.R., Russell, M.L., and Crapo, J.D.: Alveolar septal structure in different species. J. Appl. Physiol. 77, 1060 (1994).
51.Itoh, H., Nishino, M., and Hatabu, H.: Architecture of the lung: morphology and function. J. Thorac. Imaging 19, 221 (2004).
52.Weibel, E.R. and Knight, B.W.: A morphometric study on the thickness of the pulmonary air-blood barrier. J. Cell Biol. 21, 367 (1964).
53.West, J.B.: Comparative physiology of the pulmonary blood-gas barrier: the unique avian solution. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1625 (2009).
54.Roberts, M.A., Tran, D., Coulombe, K.L.K., Razumova, M., Regnier, M., Murry, C.E., and Zheng, Y.: Stromal cells in dense collagen promote cardiomyocyte and microvascular patterning in engineered human heart tissue. Tissue Eng. A 22, 633 (2016).
55.Nunes, S.S., Miklas, J.W., Liu, J., Aschar-Sobbi, R., Xiao, Y., Zhang, B., Jiang, J., Massé, S., Gagliardi, M., Hsieh, A., Thavandiran, N., Laflamme, M.A., Nanthakumar, K., Gross, G.J., Backx, P.H., Keller, G., and Radisic, M.: Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat. Methods 10, 781 (2013).
56.Badylak, S.F., Taylor, D., and Uygun, K.: Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu. Rev. Biomed. Eng. 13, 27 (2011).
57.Scarritt, M.E., Pashos, N.C., and Bunnell, B.A.: A review of cellularization strategies for tissue engineering of whole organs. Front. Bioeng. Biotechnol. 3, 43 (2015).
58.Ott, H.C., Matthiesen, T.S., Goh, S.-K., Black, L.D., Kren, S.M., Netoff, T.I., and Taylor, D.A.: Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat. Med. 14, 213 (2008).
59.Ott, H.C., Clippinger, B., Conrad, C., Schuetz, C., Pomerantseva, I., Ikonomou, L., Kotton, D., and Vacanti, J.P.: Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16, 927 (2010).
60.Petersen, T.H., Calle, E.A., Zhao, L., Lee, E.J., Gui, L., Raredon, M.B., Gavrilov, K., Yi, T., Zhuang, Z.W., Breuer, C., Herzog, E., and Niklason, L.E.: Tissue-engineered lungs for in vivo implantation. Science 329, 538 (2010).
61.Song, J.J., Guyette, J.P., Gilpin, S.E., Gonzalez, G., Vacanti, J.P., and Ott, H.C.: Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19, 646 (2013).
62.Hasan, A., Paul, A., Vrana, N.E., Zhao, X., Memic, A., Hwang, Y.-S., Dokmeci, M.R., and Khademhosseini, A.: Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 35, 7308 (2014).
63.Fatehullah, A., Tan, S.H., and Barker, N.: Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246 (2016).
64.Keane, T.J., Swinehart, I.T., and Badylak, S.F.: Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance. Methods 84, 25 (2015).
65.Nakayama, K.H., Batchelder, C.A., Lee, C.I., and Tarantal, A.F.: Decellularized rhesus monkey kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering. Tissue Eng. A 16, 2207 (2010).
66.Crapo, P.M., Gilbert, T.W., and Badylak, S.F.: An overview of tissue and whole organ decellularization processes. Biomaterials 32, 3233 (2011).
67.Wu, Q., Bao, J., Zhou, Y., Wang, Y., Du, Z., Shi, Y., Li, L., and Bu, H.: Optimizing perfusion-decellularization methods of porcine livers for clinical-scale whole-organ bioengineering. Biomed. Res. Int. 2015, 785474 (2015).
68.Malik, N. and Rao, M.S.: A review of the methods for human iPSC derivation. Methods Mol. Biol. 997, 23 (2013).
69.Shi, Y., Inoue, H., Wu, J.C., and Yamanaka, S.: Induced pluripotent stem cell technology: a decade of progress. Nat. Rev. Drug Discov. 16, 115 (2016).
70.Ren, X., Moser, P.T., Gilpin, S.E., Okamoto, T., Wu, T., Tapias, L.F., Mercier, F.E., Xiong, L., Ghawi, R., Scadden, D.T., Mathisen, D.J., and Ott, H.C.: Engineering pulmonary vasculature in decellularized rat and human lungs. Nat. Biotechnol. 33, 1097 (2015).
71.Huang, S.X.L., Islam, M.N., O'Neill, J., Hu, Z., Yang, Y.-G., Chen, Y.-W., Mumau, M., Green, M.D., Vunjak-Novakovic, G., Bhattacharya, J., and Snoeck, H.-W.: Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat. Biotechnol. 32, 84 (2013).
72.Lu, T.-Y., Lin, B., Kim, J., Sullivan, M., Tobita, K., Salama, G., and Yang, L.: Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat. Commun. 4, 2307 (2013).
73.Sutherland, M.L., Fabre, K.M., and Tagle, D.A.: The National Institutes of Health Microphysiological Systems Program focuses on a critical challenge in the drug discovery pipeline. Stem Cell Res. Ther. 4(Suppl. 1), I1 (2013).
74.Stokes, C.L., Cirit, M., and Lauffenburger, D.A.: Physiome-on-a-chip: the challenge of ‘scaling’ in design, operation, and translation of microphysiological systems. CPT Pharmacometrics Syst. Pharmacol. 4, 559 (2015).
75.Marx, U., Andersson, T.B., Bahinski, A., Beilmann, M., Beken, S., Cassee, F.R., Cirit, M., Daneshian, M., Fitzpatrick, S., Frey, O., Gaertner, C., Giese, C., Griffith, L., Hartung, T., Heringa, M.B., Hoeng, J., de Jong, W.H., Kojima, H., Kuehnl, J., Leist, M., Luch, A., Maschmeyer, I., Sakharov, D., Sips, A.J.A.M., Steger-Hartmann, T., Tagle, D.A., Tonevitsky, A., Tralau, T., Tsyb, S., van de Stolpe, A., Vandebriel, R., Vulto, P., Wang, J., Wiest, J., Rodenburg, M., and Roth, A.: Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX 33, 272 (2016).
76.Vernetti, L., Gough, A., Baetz, N., Blutt, S., Broughman, J.R., Brown, J.A., Foulke-Abel, J., Hasan, N., In, J., Kelly, E., Kovbasnjuk, O., Repper, J., Senutovitch, N., Stabb, J., Yeung, C., Zachos, N.C., Donowitz, M., Estes, M., Himmelfarb, J., Truskey, G., Wikswo, J.P., and Taylor, D.L.: Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Sci. Rep. 7, 42296 (2017).
77.Miller, P.G. and Shuler, M.L.: Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol. Bioeng. 113, 2213 (2016).
78.Qin, D., Xia, Y., and Whitesides, G.M.: Soft lithography for micro- and nanoscale patterning. Nat. Protoc. 5, 491 (2010).
79.Sia, S.K. and Whitesides, G.M.: Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies. Electrophoresis 24, 3563 (2003).
80.Berthier, E., Young, E.W.K., and Beebe, D.: Engineers are from PDMS-land, Biologists are from Polystyrenia. Lab Chip 12, 1224 (2012).
81.Xia, Y. and Whitesides, G.M.: Soft lithography. Annu. Rev. Mater. Sci. 28, 153 (1998).
82.Song, J.W., Gu, W., Futai, N., Warner, K.A., Nor, J.E., and Takayama, S.: Computer-controlled microcirculatory support system for endothelial cell culture and shearing. Anal. Chem. 77, 3993 (2005).
83.Zheng, C., Zhang, X., Li, C., Pang, Y., and Huang, Y.: Microfluidic device for studying controllable hydrodynamic flow induced cellular responses. Anal. Chem. 89, 3710 (2017).
84.Smith, Q. and Gerecht, S.: Going with the flow: microfluidic platforms in vascular tissue engineering. Curr. Opin. Chem. Eng. 3, 42 (2014).
85.Lee, S.A., Chung, S.E., Park, W., Lee, S.H., and Kwon, S.: Three-dimensional fabrication of heterogeneous microstructures using soft membrane deformation and optofluidic maskless lithography. Lab Chip 9, 1670 (2009).
86.Chueh, B., Huh, D., Kyrtsos, C.R., Houssin, T., Futai, N., and Takayama, S.: Leakage-free bonding of porous membranes into layered microfluidic array systems. Anal. Chem. 79, 3504 (2007).
87.Huh, D., Matthews, B.D., Mammoto, A., Montoya-Zavala, M., Hsin, H.Y., and Ingber, D.E.: Reconstituting organ-level lung functions on a chip. Science 328, 1662 (2010).
88.Kane, R.: Patterning proteins and cells using soft lithography. Biomaterials 20, 2363 (1999).
89.Dittrich, P.S. and Manz, A.: Lab-on-a-chip: microfluidics in drug discovery. Nat. Rev. Drug Discov. 5, 210 (2006).
90.Khademhosseini, A., Langer, R., Borenstein, J., and Vacanti, J.P.: Microscale technologies for tissue engineering and biology. Proc. Natl. Acad. Sci. U. S. A. 103, 2480 (2006).
91.Jang, K.-J., Mehr, A.P., Hamilton, G.A., McPartlin, L.A., Chung, S., Suh, K.-Y., and Ingber, D.E.: Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr. Biol. 5, 1119 (2013).
92.Kim, S., LesherPerez, S.C., Kim, B.C., Yamanishi, C., Labuz, J.M., Leung, B., and Takayama, S.: Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication 8, 15021 (2016).
93.Gori, M., Simonelli, M.C., Giannitelli, S.M., Businaro, L., Trombetta, M., and Rainer, A.: Investigating nonalcoholic fatty liver disease in a liver-on-a-chip microfluidic device. PLoS ONE 11, e0159729 (2016).
94.Benam, K.H., Villenave, R., Lucchesi, C., Varone, A., Hubeau, C., Lee, H.-H., Alves, S.E., Salmon, M., Ferrante, T.C., Weaver, J.C., Bahinski, A., Hamilton, G.A., and Ingber, D.E.: Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat. Methods 13, 151 (2015).
95.Lee, P.J., Hung, P.J., and Lee, L.P.: An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol. Bioeng. 97, 1340 (2007).
96.Legendre, A., Baudoin, R., Alberto, G., Paullier, P., Naudot, M., Bricks, T., Brocheton, J., Jacques, S., Cotton, J., and Leclerc, E.: Metabolic characterization of primary rat hepatocytes cultivated in parallel microfluidic biochips. J. Pharm. Sci. 102, 3264 (2013).
97.Kim, D.-H., Lipke, E.A., Kim, P., Cheong, R., Thompson, S., Delannoy, M., Suh, K.-Y., Tung, L., and Levchenko, A.: Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc. Natl. Acad. Sci. U. S. A. 107, 565 (2010).
98.Tanaka, Y., Sato, K., Shimizu, T., Yamato, M., Okano, T., Kitamori, T., Healy, K.E., Folch, A., and Okano, T.: A micro-spherical heart pump powered by cultured cardiomyocytes. Lab Chip 7, 207 (2007).
99.Carson, D., Hnilova, M., Yang, X., Nemeth, C.L., Tsui, J.H., Smith, A.S.T., Jiao, A., Regnier, M., Murry, C.E., Tamerler, C., and Kim, D.-H.: Nanotopography-induced structural anisotropy and sarcomere development in human cardiomyocytes derived from induced pluripotent stem cells. ACS Appl. Mater. Interfaces 8, 21923 (2016).
100.Macadangdang, J., Guan, X., Smith, A.S.T., Lucero, R., Czerniecki, S., Childers, M.K., Mack, D.L., and Kim, D.-H.: Nanopatterned human iPSC-based model of a dystrophin-null cardiomyopathic phenotype. Cell. Mol. Bioeng. 8, 320 (2015).
101.Slaughter, B.V., Khurshid, S.S., Fisher, O.Z., Khademhosseini, A., and Peppas, N.A.: Hydrogels in regenerative medicine. Adv. Mater. 21, 3307 (2009).
102.Griffith, L.G. and Swartz, M.A.: Capturing complex 3D tissue physiology in vitro. Nat. Rev. Mol. Cell Biol. 7, 211 (2006).
103.O'Brien, F.J.: Biomaterials & scaffolds for tissue engineering. Mater. Today 14, 88 (2011).
104.Tien, J.: Microfluidic approaches for engineering vasculature. Curr. Opin. Chem. Eng. 3, 36 (2014).
105.Chrobak, K.M., Potter, D.R., and Tien, J.: Formation of perfused, functional microvascular tubes in vitro. Microvasc. Res. 71, 185 (2006).
106.Wong, K.H.K., Truslow, J.G., Khankhel, A.H., Chan, K.L.S., and Tien, J.: Artificial lymphatic drainage systems for vascularized microfluidic scaffolds. J. Biomed. Mater. Res. A 101A, 2181 (2013).
107.Golden, A.P. and Tien, J.: Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 7, 720 (2007).
108.Miller, J.S., Stevens, K.R., Yang, M.T., Baker, B.M., Nguyen, D.-H.T., Cohen, D.M., Toro, E., Chen, A.A., Galie, P.A., Yu, X., Chaturvedi, R., Bhatia, S.N., and Chen, C.S.: Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768 (2012).
109.Huling, J., Ko, I.K., Atala, A., and Yoo, J.J.: Fabrication of biomimetic vascular scaffolds for 3D tissue constructs using vascular corrosion casts. Acta Biomater. 32, 190 (2016).
110.Zheng, Y., Chen, J., Craven, M., Choi, N.W., Totorica, S., Diaz-Santana, A., Kermani, P., Hempstead, B., Fischbach-Teschl, C., López, J.A., and Stroock, A.D.: In vitro microvessels for the study of angiogenesis and thrombosis. Proc. Natl. Acad. Sci. U. S. A. 109, 9342 (2012).
111.Zhang, B., Montgomery, M., Chamberlain, M.D., Ogawa, S., Korolj, A., Pahnke, A., Wells, L.A., Massé, S., Kim, J., Reis, L., Momen, A., Nunes, S.S., Wheeler, A.R., Nanthakumar, K., Keller, G., Sefton, M.V., and Radisic, M.: Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15, 669 (2016).
112.Lee, E.J., Kim, D.E., Azeloglu, E.U., and Costa, K.D.: Engineered cardiac organoid chambers: toward a functional biological model ventricle. Tissue Eng. A 14, 215 (2008).
113.Bajaj, P., Schweller, R.M., Khademhosseini, A., West, J.L., and Bashir, R.: 3D biofabrication strategies for tissue engineering and regenerative medicine. Annu. Rev. Biomed. Eng. 16, 247 (2014).
114.Vernetti, L.A., Senutovitch, N., Boltz, R., DeBiasio, R., Ying Shun, T., Gough, A., and Taylor, D.L.: A human liver microphysiology platform for investigating physiology, drug safety, and disease models. Exp. Biol. Med. 241, 101 (2016).
115.Ligresti, G., Nagao, R.J., Xue, J., Choi, Y.J., Xu, J., Ren, S., Aburatani, T., Anderson, S.K., MacDonald, J.W., Bammler, T.K., Schwartz, S.M., Muczynski, K.A., Duffield, J.S., Himmelfarb, J., and Zheng, Y.: A Novel three-dimensional human peritubular microvascular system. J. Am. Soc. Nephrol. 27, 2370 (2016).
116.Chaturvedi, R.R., Stevens, K.R., Solorzano, R.D., Schwartz, R.E., Eyckmans, J., Baranski, J.D., Stapleton, S.C., Bhatia, S.N., and Chen, C.S.: Patterning vascular networks in vivo for tissue engineering applications. Tissue Eng. C Methods 21, 509 (2015).
117.Mihic, A., Li, J., Miyagi, Y., Gagliardi, M., Li, S.-H., Zu, J., Weisel, R.D., Keller, G., and Li, R.-K.: The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials 35, 2798 (2014).
118.Tulloch, N.L., Muskheli, V., Razumova, M.V., Korte, F.S., Regnier, M., Hauch, K.D., Pabon, L., Reinecke, H., and Murry, C.E.: Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ. Res. 109, 47 (2011).
119.Murphy, S.V., Skardal, A., and Atala, A.: Evaluation of hydrogels for bio-printing applications. J. Biomed. Mater. Res. A 101A, 272 (2013).
120.Skardal, A. and Atala, A.: Biomaterials for Integration with 3-D bioprinting. Ann. Biomed. Eng. 43, 730 (2014).
121.Pati, F., Jang, J., Ha, D.-H., Won Kim, S., Rhie, J.-W., Shim, J.-H., Kim, D.-H., and Cho, D.-W.: Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat. Commun. 5, 3935 (2014).
122.He, Y., Yang, F., Zhao, H., Gao, Q., Xia, B., and Fu, J.: Research on the printability of hydrogels in 3D bioprinting. Sci. Rep. 6, 29977 (2016).
123.Ahmed, E.M.: Hydrogel: preparation, characterization, and applications: a review. J. Adv. Res. 6, 105 (2015).
124.Rutz, A.L., Hyland, K.E., Jakus, A.E., Burghardt, W.R., and Shah, R.N.: A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv. Mater. 27, 1607 (2015).
125.Skardal, A., Devarasetty, M., Kang, H.-W., Mead, I., Bishop, C., Shupe, T., Lee, S.J., Jackson, J., Yoo, J., Soker, S., and Atala, A.: A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. Acta Biomater. 25, 24 (2015).
126.Mandrycky, C., Wang, Z., Kim, K., and Kim, D.-H.: 3D bioprinting for engineering complex tissues. Biotechnol. Adv. 34, 422 (2016).
127.Ozbolat, I.T. and Hospodiuk, M.: Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 76, 321 (2016).
128.Raman, R. and Bashir, R.: Chapter 6—stereolithographic 3D bioprinting for biomedical applications. In Essentials of 3D Biofabrication and Translation, edited by A. Atala and J.J. Yoo (Academic Press, 2015), pp. 89121.
129.Homan, K.A., Kolesky, D.B., Skylar-Scott, M.A., Herrmann, J., Obuobi, H., Moisan, A., and Lewis, J.A.: Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci. Rep. 6, 34845 (2016).
130.Ma, X., Qu, X., Zhu, W., Li, Y.-S., Yuan, S., Zhang, H., Liu, J., Wang, P., Lai, C.S.E., Zanella, F., Feng, G.-S., Sheikh, F., Chien, S., and Chen, S.: Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proc. Natl. Acad. Sci. U. S. A. 113, 2206 (2016).
131.Horváth, L., Umehara, Y., Jud, C., Blank, F., Petri-Fink, A., and Rothen-Rutishauser, B.: Engineering an in vitro air-blood barrier by 3D bioprinting. Sci. Rep. 5, 7974 (2015).
132.Faulkner-Jones, A., Fyfe, C., Cornelissen, D.-J., Gardner, J., King, J., Courtney, A., and Shu, W.: Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D. Biofabrication 7, 44102 (2015).
133.Nguyen, D.G., Funk, J., Robbins, J.B., Crogan-Grundy, C., Presnell, S.C., Singer, T., and Roth, A.B.: Bioprinted 3D primary liver tissues allow assessment of organ-level response to clinical drug induced toxicity in vitro. PLoS ONE 11, e0158674 (2016).
134.Bhise, N.S., Manoharan, V., Massa, S., Tamayol, A., Ghaderi, M., Miscuglio, M., Lang, Q., Shrike Zhang, Y., Shin, S.R., Calzone, G., Annabi, N., Shupe, T.D., Bishop, C.E., Atala, A., Dokmeci, M.R., and Khademhosseini, A.: A liver-on-a-chip platform with bioprinted hepatic spheroids. Biofabrication 8, 14101 (2016).
135.Gaetani, R., Doevendans, P.A., Metz, C.H.G., Alblas, J., Messina, E., Giacomello, A., and Sluijter, J.P.G.: Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells. Biomaterials 33, 1782 (2012).
136.Gaetani, R., Feyen, D.A.M., Verhage, V., Slaats, R., Messina, E., Christman, K.L., Giacomello, A., Doevendans, P.A.F.M., and Sluijter, J.P.G.: Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials 61, 339 (2015).
137.Zhang, Y.S., Arneri, A., Bersini, S., Shin, S.-R., Zhu, K., Goli-Malekabadi, Z., Aleman, J., Colosi, C., Busignani, F., Dell'Erba, V., Bishop, C., Shupe, T., Demarchi, D., Moretti, M., Rasponi, M., Dokmeci, M.R., Atala, A., and Khademhosseini, A.: Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials 110, 45 (2016).
138.Takasato, M., Er, P.X., Chiu, H.S., Maier, B., Baillie, G.J., Ferguson, C., Parton, R.G., Wolvetang, E.J., Roost, M.S., Chuva de Sousa Lopes, S.M., and Little, M.H.: Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 564 (2015).
139.Morizane, R., Lam, A.Q., Freedman, B.S., Kishi, S., Valerius, M.T., and Bonventre, J.V.: Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat. Biotechnol. 33, 1193 (2015).
140.Freedman, B.S., Brooks, C.R., Lam, A.Q., Fu, H., Morizane, R., Agrawal, V., Saad, A.F., Li, M.K., Hughes, M.R., Vander Werff, R., Peters, D.T., Lu, J., Baccei, A., Siedlecki, A.M., Valerius, M.T., Musunuru, K., McNagny, K.M., Steinman, T.I., Zhou, J., Lerou, P.H., and Bonventre, J.V.: Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat. Commun. 6, 8715 (2015).
141.Huch, M., Dorrell, C., Boj, S.F., van Es, J.H., Li, V.S.W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M.J., Haft, A., Vries, R.R.G., Grompe, M., and Clevers, H.: In vitro expansion of single Lgr5+ liver stem cells induced by WNT-driven regeneration. Nature 494, 247 (2013).
142.Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., Aoyama, S., Adachi, Y., and Taniguchi, H.: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481 (2013).
143.Khademhosseini, A., Eng, G., Yeh, J., Kucharczyk, P.A., Langer, R., Vunjak-Novakovic, G., and Radisic, M.: Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed. Microdevices 9, 149 (2007).
144.Iyer, R.K., Chui, J., and Radisic, M.: Spatiotemporal tracking of cells in tissue-engineered cardiac organoids. J. Tissue Eng. Regen. Med. 3, 196 (2009).
145.Voges, H.K., Mills, R.J., Elliott, D.A., Parton, R.G., Porrello, E.R., and Hudson, J.E.: Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 144, 1118 (2017).
146.Dye, B.R., Hill, D.R., Ferguson, M.A., Tsai, Y.-H., Nagy, M.S., Dyal, R., Wells, J.M., Mayhew, C.N., Nattiv, R., Klein, O.D., White, E.S., Deutsch, G.H., Spence, J.R., Shroyer, N., Wells, J., Helmrath, M., Kotton, D., Elefanty, A., Stanley, E., Chen, Q., Prabhakar, S., Weissman, I., and Lim, B.: In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4, 327 (2015).
147.Dye, B.R., Dedhia, P.H., Miller, A.J., Nagy, M.S., White, E.S., Shea, L.D., Spence, J.R., Ellis, J., Rossant, J., Sun, Y., Grabowski, G., Finkbeiner, S., Spence, J., Shroyer, N., Wells, J., Helmrath, M., Mense, M., Rowe, S., Engelhardt, J., Hsu, Y., and Rajagopal, J.: A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Elife 5, 876 (2016).
148.Takahashi, H., Nakayama, M., Shimizu, T., Yamato, M., and Okano, T.: Anisotropic cell sheets for constructing three-dimensional tissue with well-organized cell orientation. Biomaterials 32, 8830 (2011).
149.Jiao, A., Trosper, N.E., Yang, H.S., Kim, J., Tsui, J.H., Frankel, S.D., Murry, C.E., and Kim, D.-H.: Thermoresponsive nanofabricated substratum for the engineering of three-dimensional tissues with layer-by-layer architectural control. ACS Nano 8, 4430 (2014).
150.Gupta, R., Van Rooijen, N., and Sefton, M.V.: Fate of endothelialized modular constructs implanted in an omental pouch in nude rats. Tissue Eng. A 15, 2875 (2009).
151.Rafii, S., Butler, J.M., and Ding, B.-S.: Angiocrine functions of organ-specific endothelial cells. Nature 529, 316 (2016).
152.Tabar, V. and Studer, L.: Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat. Rev. Genet. 15, 82 (2014).
153.Engler, A.J., Sen, S., Sweeney, H.L., and Discher, D.E.: Matrix elasticity directs stem cell lineage specification. Cell 126, 677 (2006).
154.Briquez, P.S., Clegg, L.E., Martino, M.M., Mac Gabhann, F., and Hubbell, J.A.: Design principles for therapeutic angiogenic materials. Nat. Rev. Mater. 1, 15006 (2016).
155.Asti, A. and Gioglio, L.: Natural and synthetic biodegradable polymers: different scaffolds for cell expansion and tissue formation. Int. J. Artif. Organs 37, 187 (2014).
156.Gilpin, A. and Yang, Y.: Decellularization strategies for regenerative medicine: from processing techniques to applications. Biomed Res. Int. 2017, 1 (2017).
157.Saldin, L.T., Cramer, M.C., Velankar, S.S., White, L.J., and Badylak, S.F.: Extracellular matrix hydrogels from decellularized tissues: structure and function. Acta Biomater. 49, 1 (2017).

Related content

Powered by UNSILO

Tissue engineering toward organ-specific regeneration and disease modeling

  • Christian Mandrycky (a1), Kiet Phong (a1) and Ying Zheng (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.