Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Multiscale technologies for treatment of ischemic cardiomyopathy

Abstract

The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease. We also discuss emerging trends in nanotechnology affecting the cardiovascular field that may offer new hope for patients suffering massive heart attacks.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Applications of various nanoplatforms in the prevention and treatment of cardiovascular disease.
Figure 2: Dual-antibody-conjugated magnetic nanoparticles target therapeutic cells and regenerate the injured myocardium.
Figure 3: The use of a living contrast agent, MEs derived from magnetotactic bacteria, for safe labelling and precise monitoring of CMs.
Figure 4: Application of nanostructured cardiac patch device in repair/regeneration of MI.

Similar content being viewed by others

References

  1. Bui, A. L., Horwich, T. B. & Fonarow, G. C. Epidemiology and risk profile of heart failure. Nat. Rev. Cardiol. 8, 30–41 (2011).

    Article  Google Scholar 

  2. Johnson, N. B. et al. CDC National Health Report: leading causes of morbidity and mortality and associated behavioral risk and protective factors—United States, 2005–2013. MMWR Surveill. Summ. 63, 3–27 (2014).

    Google Scholar 

  3. Thygesen, K., Alpert, J. S. & White, H. D. Universal definition of myocardial infarction. J. Am. Coll. Cardiol. 50, 2173–2195 (2007).

    Article  Google Scholar 

  4. Cassar, A., Holmes, D. R. Jr., Rihal, C. S. & Gersh, B. J. Chronic coronary artery disease: diagnosis and management. Mayo Clin. Proc. 84, 1130–1146 (2009).

    Article  CAS  Google Scholar 

  5. White, H. D. & Chew, D. P. Acute myocardial infarction. Lancet 372, 570–584 (2008).

    Article  CAS  Google Scholar 

  6. Senyo, S. E. et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493, 433–436 (2013).

    Article  CAS  Google Scholar 

  7. Ziaeian, B. & Fonarow, G. C. Epidemiology and aetiology of heart failure. Nat. Rev. Cardiol. 13, 368–378 (2016).

    Article  Google Scholar 

  8. Dunlay, S. M. & Roger, V. L. Understanding the epidemic of heart failure: past, present, and future. Curr. Heart Fail. Rep. 11, 404–415 (2014).

    Article  Google Scholar 

  9. Wijns, W. et al. Guidelines on myocardial revascularization. Eur. Heart J. 31, 2501–2555 (2010).

    Article  Google Scholar 

  10. Libby, P., Ridker, P. M. & Maseri, A. Inflammation and atherosclerosis. Circulation 105, 1135–1143 (2002).

    Article  CAS  Google Scholar 

  11. Nabel, E. G. & Braunwald, E. A tale of coronary artery disease and myocardial infarction. N. Engl. J. Med. 366, 54–63 (2012).

    Article  CAS  Google Scholar 

  12. Libby, P., Ridker, P. M. & Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325 (2011).

    Article  CAS  Google Scholar 

  13. Begum, M. & Sharma, H. Scope of nanomedicine against coronary artery disease: a review. Eur. J. Pharm. Med. Res. 3, 635–641 (2016).

    Google Scholar 

  14. Mahmoudi, M. et al. Protein−nanoparticle interactions: opportunities and challenges. Chem. Rev. 111, 5610–5637 (2011).

    Article  CAS  Google Scholar 

  15. Nahrendorf, M. et al. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 117, 379–387 (2008).

    Article  CAS  Google Scholar 

  16. Mahmoudi, M., Serpooshan, V. & Laurent, S. Engineered nanoparticles for biomolecular imaging. Nanoscale 3, 3007–3026 (2011).

    Article  CAS  Google Scholar 

  17. Sanz, J. & Fayad, Z. A. Imaging of atherosclerotic cardiovascular disease. Nature 451, 953–957 (2008).

    Article  CAS  Google Scholar 

  18. Zanganeh, S. et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotech. 11, 986–994 (2016).

    Article  CAS  Google Scholar 

  19. Lobatto, M. E., Fuster, V., Fayad, Z. A. & Mulder, W. J. Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat. Rev. Drug Discov. 10, 835–852 (2011).

    Article  CAS  Google Scholar 

  20. Korin, N. et al. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 337, 738–742 (2012).

    Article  CAS  Google Scholar 

  21. Fredman, G. et al. Targeted nanoparticles containing the proresolving peptide Ac2–26 protect against advanced atherosclerosis in hypercholesterolemic mice. Sci. Transl. Med. 7, 275ra220 (2015).

    Google Scholar 

  22. Kamaly, N. et al. Targeted interleukin-10 nanotherapeutics developed with a microfluidic chip enhance resolution of inflammation in advanced atherosclerosis. ACS Nano 10, 5280–5292 (2016).

    Article  CAS  Google Scholar 

  23. Kamaly, N. et al. Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles. Proc. Natl Acad. Sci. USA 110, 6506–6511 (2013).

    Article  CAS  Google Scholar 

  24. Kamaly, N., He, J. C., Ausiello, D. A. & Farokhzad, O. C. Nanomedicines for renal disease: current status and future applications. Nat. Rev. Nephrol. 12, 738–753 (2016).

    Article  CAS  Google Scholar 

  25. Duivenvoorden, R. et al. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. Nat. Commun. 5, 3531 (2014).

    Article  CAS  Google Scholar 

  26. Chan, J. M. et al. Spatiotemporal controlled delivery of nanoparticles to injured vasculature. Proc. Natl Acad. Sci. USA 107, 2213–2218 (2010).

    Article  CAS  Google Scholar 

  27. Chnari, E., Nikitczuk, J. S., Wang, J., Uhrich, K. E. & Moghe, P. V. Engineered polymeric nanoparticles for receptor-targeted blockage of oxidized low density lipoprotein uptake and atherogenesis in macrophages. Biomacromolecules 7, 1796–1805 (2006).

    Article  CAS  Google Scholar 

  28. Lewis, D. R. et al. Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo. Proc. Natl Acad. Sci. USA 112, 2693–2698 (2015).

    Article  CAS  Google Scholar 

  29. Tomasini, M. D., Zablocki, K., Petersen, L. K., Moghe, P. V. & Tomassone, M. S. Coarse grained molecular dynamics of engineered macromolecules for the inhibition of oxidized low-density lipoprotein uptake by macrophage scavenger receptors. Biomacromolecules 14, 2499–2509 (2013).

    Article  CAS  Google Scholar 

  30. Monopoli, M. P., Åberg, C., Salvati, A. & Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotech. 7, 779–786 (2012).

    Article  CAS  Google Scholar 

  31. Mahmoudi, M. Protein corona: The golden gate to clinical applications of nanoparticles. Int. J. Biochem. Cell Biol. 75, 141–142 (2016).

    Article  CAS  Google Scholar 

  32. Caracciolo, G., Farokhzad, O. C. & Mahmoudi, M. Biological identity of nanoparticles in vivo: clinical implications of the protein corona. Trends Biotechnol. 35, 257–264 (2017).

    Article  CAS  Google Scholar 

  33. Salvati, A. et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotech. 7, 779–786 (2012).

    Article  CAS  Google Scholar 

  34. Mirshafiee, V., Mahmoudi, M., Lou, K., Cheng, J. & Kraft, M. L. Protein corona significantly reduces active targeting yield. Chem. Commun. 49, 2557–2559 (2013).

    Article  CAS  Google Scholar 

  35. Behzadi, S. et al. Protein corona change the drug release profile of nanocarriers: the “overlooked” factor at the nanobio interface. Colloids Surf. B 123, 143–149 (2014).

    Article  CAS  Google Scholar 

  36. Moyano, D. F. et al. Fabrication of corona-free nanoparticles with tunable hydrophobicity. ACS Nano 8, 6748–6755 (2014).

    Article  CAS  Google Scholar 

  37. Mirshafiee, V., Kim, R., Park, S., Mahmoudi, M. & Kraft, M. L. Impact of protein pre-coating on the protein corona composition and nanoparticle cellular uptake. Biomaterials 75, 295–304 (2016).

    Article  CAS  Google Scholar 

  38. Deng, Z. J., Liang, M., Monteiro, M., Toth, I. & Minchin, R. F. Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nat. Nanotech. 6, 39–44 (2011).

    Article  CAS  Google Scholar 

  39. Behfar, A., Crespo-Diaz, R., Terzic, A. & Gersh, B. J. Cell therapy for cardiac repair—lessons from clinical trials. Nat. Rev. Cardiol. 11, 232–246 (2014).

    Article  Google Scholar 

  40. Nguyen, P. K., Rhee, J. W. & Wu, J. C. Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review. JAMA Cardiol. 1, 831–841 (2016).

    Article  Google Scholar 

  41. Burridge, P. W., Keller, G., Gold, J. D. & Wu, J. C. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10, 16–28 (2012).

    Article  CAS  Google Scholar 

  42. Ranganath, S. H., Levy, O., Inamdar, M. S. & Karp, J. M. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10, 244–258 (2012).

    Article  CAS  Google Scholar 

  43. Nguyen, P. K., Neofytou, E., Rhee, J.-W. & Wu, J. C. Potential strategies to address the major clinical barriers facing stem cell regenerative therapy for cardiovascular disease: a review. JAMA Cardiol. 1, 953–962 (2016).

    Article  Google Scholar 

  44. Mahmoudi, M. et al. Novel MRI contrast agent from magnetotactic bacteria enables in vivo tracking of iPSC-derived cardiomyocytes. Sci. Rep. 6, 26960 (2016).

    Article  CAS  Google Scholar 

  45. Chong, J. J. et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510, 273–277 (2014).

    Article  CAS  Google Scholar 

  46. Riegler, J. et al. Comparison of magnetic resonance imaging and serum biomarkers for detection of human pluripotent stem cell-derived teratomas. Stem Cell Rep. 6, 176–187 (2016).

    Article  CAS  Google Scholar 

  47. Burridge, P. W. et al. Chemically defined generation of human cardiomyocytes. Nat. Methods 11, 855–860 (2014).

    Article  CAS  Google Scholar 

  48. Cheng, K. et al. Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting. Nat. Commun. 5, 4880 (2014).

    Article  CAS  Google Scholar 

  49. Shiba, Y. et al. Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature 489, 322–325 (2012).

    Article  CAS  Google Scholar 

  50. Kawamura, M. et al. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126, S29–S37 (2012).

    Article  CAS  Google Scholar 

  51. Laflamme, M. A. & Murry, C. E. Heart regeneration. Nature 473, 326–335 (2011).

    Article  CAS  Google Scholar 

  52. Mirotsou, M. et al. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc. Natl Acad. Sci. USA 104, 1643–1648 (2007).

    Article  CAS  Google Scholar 

  53. Han, J. et al. Iron oxide nanoparticle-mediated development of cellular gap junction crosstalk to improve mesenchymal stem cells' therapeutic efficacy for myocardial infarction. ACS Nano 9, 2805–2819 (2015).

    Article  CAS  Google Scholar 

  54. Vandergriff, A. C. et al. Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction. Biomaterials 35, 8528–8539 (2014).

    Article  CAS  Google Scholar 

  55. Xu, C. et al. Tracking mesenchymal stem cells with iron oxide nanoparticle loaded poly (lactide-co-glycolide) microparticles. Nano Lett. 12, 4131–4139 (2012).

    Article  CAS  Google Scholar 

  56. Yang, X. Magnetic Resonance Imaging of Stem Cell Applications (Nova Science, 2015).

    Google Scholar 

  57. Mahmoudi, M., Bertrand, N., Zope, H. & Farokhzad, O. Emerging understanding of the nano-bio interface in nanomedicin. Nano Today 11, 817–832 (2016).

    Article  CAS  Google Scholar 

  58. Chen, I. Y. et al. Comparison of optical bioluminescence reporter gene and superparamagnetic iron oxide MR contrast agent as cell markers for noninvasive imaging of cardiac cell transplantation. Mol. Imaging Biol. 11, 178–187 (2009).

    Article  Google Scholar 

  59. Terrovitis, J. et al. Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation 117, 1555–1562 (2008).

    Article  Google Scholar 

  60. Nguyen, P. K., Riegler, J. & Wu, J. C. Stem cell imaging: from bench to bedside. Cell Stem Cell 14, 431–444 (2014).

    Article  CAS  Google Scholar 

  61. Takahama, H. et al. Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model. Cardiovasc. Drugs Ther. 27, 125–132 (2013).

    Article  CAS  Google Scholar 

  62. Ewer, M. S. & Ewer, S. M. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat. Rev. Cardiol. 7, 564–575 (2010).

    Article  Google Scholar 

  63. Burridge, P. et al. Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity. Nat. Med. 22, 547–556 (2016).

    Article  CAS  Google Scholar 

  64. Louch, W. E., Sheehan, K. A. & Wolska, B. M. Methods in cardiomyocyte isolation, culture, and gene transfer. J. Mol. Cell. Cardiol. 51, 288–298 (2011).

    Article  CAS  Google Scholar 

  65. Yang, X., Pabon, L. & Murry, C. E. Engineering adolescence maturation of human pluripotent stem cell–derived cardiomyocytes. Circ. Res. 114, 511–523 (2014).

    Article  CAS  Google Scholar 

  66. Kattman, S. J. et al. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8, 228–240 (2011).

    Article  CAS  Google Scholar 

  67. Sharma, A. et al. High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci. Transl. Med. 9, eaaf2584 (2017).

    Article  CAS  Google Scholar 

  68. Wei, K. et al. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525, 479–485 (2015).

    Article  CAS  Google Scholar 

  69. Ribeiro, A. J. et al. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc. Natl Acad. Sci. USA 112, 12705–12710 (2015).

    Article  CAS  Google Scholar 

  70. Sayed, N., Liu, C. & Wu, J. C. Translation of human-induced pluripotent stem cells: from clinical trial in a dish to precision medicine. J. Am. Coll. Cardiol. 67, 2161–2176 (2016).

    Article  Google Scholar 

  71. O'Cearbhaill, E. D., Ng, K. S. & Karp, J. Emerging medical devices for minimally invasive cell therapy. Mayo Clin. Proc. 89, 259–273 (2014).

    Article  Google Scholar 

  72. Wang, G. et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat. Med. 20, 616–623 (2014).

    Article  CAS  Google Scholar 

  73. Yang, H. S. et al. Electroconductive nanopatterned substrates for enhanced myogenic differentiation and maturation. Adv. Healthcare Mater. 5, 137–145 (2016).

    Article  CAS  Google Scholar 

  74. Wang, P.-Y., Yu, J., Lin, J.-H. & Tsai, W.-B. Modulation of alignment, elongation and contraction of cardiomyocytes through a combination of nanotopography and rigidity of substrates. Acta Biomater. 7, 3285–3293 (2011).

    Article  CAS  Google Scholar 

  75. Macadangdang, J. et al. Nanopatterned human iPSC-based model of a dystrophin-null cardiomyopathic phenotype. Cell. Mol. Bioeng. 8, 320–332 (2015).

    Article  CAS  Google Scholar 

  76. Carson, D. et al. Nanotopography-induced structural anisotropy and sarcomere development in human cardiomyocytes derived from induced pluripotent stem cells. ACS Appl. Mater. Interfaces 8, 21923–21932 (2016).

    Article  CAS  Google Scholar 

  77. French, A. et al. Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards. Stem Cells Transl. Med. 4, 217–223 (2015).

    Article  CAS  Google Scholar 

  78. Laflamme, M. A. et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat. Biotechnol. 25, 1015–1024 (2007).

    Article  CAS  Google Scholar 

  79. Mashinchian, O. et al. Regulation of stem cell fate by nanomaterial substrates. Nanomedicine 10, 829–847 (2015).

    Article  CAS  Google Scholar 

  80. Mahmoudi, M. et al. Cell-imprinted substrates direct the fate of stem cells. ACS Nano 7, 8379–8384 (2013).

    Article  CAS  Google Scholar 

  81. Mashinchian, O. et al. Cell-imprinted substrates act as an artificial niche for skin regeneration. ACS Appl. Mater. Interfaces 6, 13280–13292 (2014).

    Article  CAS  Google Scholar 

  82. Bonakdar, S. et al. Cell-imprinted substrates modulate differentiation, redifferentiation, and transdifferentiation. ACS Appl. Mater. Interfaces 8, 13777–13784 (2016).

    Article  CAS  Google Scholar 

  83. Wekerle, T. & Grinyó, J. M. Belatacept: from rational design to clinical application. Transpl. Int. 25, 139–150 (2012).

    Article  CAS  Google Scholar 

  84. Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).

    Article  CAS  Google Scholar 

  85. Rong, Z. et al. An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell 14, 121–130 (2014).

    Article  CAS  Google Scholar 

  86. Uyttenhove, C. et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. Nat. Med. 9, 1269–1274 (2003).

    Article  CAS  Google Scholar 

  87. Evans, C. W., Iyer, K. S. & Hool, L. C. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart. Nanomedicine 11, 817–832 (2016).

    Article  CAS  Google Scholar 

  88. Heusch, G. et al. Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383, 1933–1943 (2014).

    Article  Google Scholar 

  89. Dvir, T. et al. Nanoparticles targeting the infarcted heart. Nano Lett. 11, 4411–4414 (2011).

    Article  CAS  Google Scholar 

  90. Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986).

    CAS  Google Scholar 

  91. Gerlowski, L. E. & Jain, R. K. Microvascular permeability of normal and neoplastic tissues. Microvasc. Res. 31, 288–305 (1986).

    Article  CAS  Google Scholar 

  92. Bertrand, N., Wu, J., Xu, X., Kamaly, N. & Farokhzad, O. C. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Delivery Rev. 66, 2–25 (2014).

    Article  CAS  Google Scholar 

  93. Maeda, H. Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Adv. Drug Delivery Rev. 91, 3–6 (2015).

    Article  CAS  Google Scholar 

  94. Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).

    Article  CAS  Google Scholar 

  95. Hardy, N. et al. Nanoparticle-mediated dual delivery of an antioxidant and a peptide against the L-Type Ca2+ channel enables simultaneous reduction of cardiac ischemia-reperfusion injury. ACS Nano 9, 279–289 (2014).

    Article  CAS  Google Scholar 

  96. Leuschner, F. et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat. Biotechnol. 29, 1005–1010 (2011).

    Article  CAS  Google Scholar 

  97. Force, T., Krause, D. S. & Van Etten, R. A. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 7, 332–344 (2007).

    Article  CAS  Google Scholar 

  98. Yeh, E. T. H. et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation 109, 3122–3131 (2004).

    Article  Google Scholar 

  99. Nasr, M., Nafee, N., Saad, H. & Kazem, A. Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice. Eur. J. Pharm. Biopharm. 88, 216–225 (2014).

    Article  CAS  Google Scholar 

  100. Setyawati, M. et al. Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin. Nat. Commun. 4, 1673 (2013).

    Article  CAS  Google Scholar 

  101. Smith, I., Liu, X., Smith, L. & Ma, P. Nanostructured polymer scaffolds for tissue engineering and regenerative medicine. Interdiscip. Rev. Nanomed. Nanobiotechnol. 1, 226–236 (2009).

    Article  CAS  Google Scholar 

  102. Dvir, T., Timko, B. P., Kohane, D. S. & Langer, R. Nanotechnological strategies for engineering complex tissues. Nat. Nanotech. 6, 13–22 (2011).

    Article  CAS  Google Scholar 

  103. Patel, D. N. & Bailey, S. R. Nanotechnology in cardiovascular medicine. Catheter. Cardiovasc. Interv. 69, 643–654 (2007).

    Article  Google Scholar 

  104. Iverson, N., Plourde, N., Chnari, E., Nackman, G. B. & Moghe, P. V. Convergence of nanotechnology and cardiovascular medicine. BioDrugs 22, 1–10 (2008).

    Article  CAS  Google Scholar 

  105. Riegler, J. et al. Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model. Circ. Res. 117, 720–730 (2015).

    Article  CAS  Google Scholar 

  106. Serpooshan, V. et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials 34, 9048–9055 (2013).

    Article  CAS  Google Scholar 

  107. Hasan, A. et al. Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv. Sci. 2, 1500122 (2015).

    Article  CAS  Google Scholar 

  108. Engelmayr, G. C. et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat. Mater. 7, 1003–1010 (2008).

    Article  CAS  Google Scholar 

  109. Souza, G. R. et al. Three-dimensional tissue culture based on magnetic cell levitation. Nat. Nanotech. 5, 291–296 (2010).

    Article  CAS  Google Scholar 

  110. Dvir, T. et al. Nanowired three-dimensional cardiac patches. Nat. Nanotech. 6, 720–725 (2011).

    Article  CAS  Google Scholar 

  111. Feiner, R. et al. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function. Nat. Mater. 15, 679–85 (2016).

    Article  CAS  Google Scholar 

  112. Bursac, N., Loo, Y., Leong, K. & Tung, L. Novel anisotropic engineered cardiac tissues: studies of electrical propagation. Biochem. Biophys. Res. Commun. 361, 847–853 (2007).

    Article  CAS  Google Scholar 

  113. Timko, B. P., Cohen-Karni, T., Qing, Q., Tian, B. & Lieber, C. M. Design and implementation of functional nanoelectronic interfaces with biomolecules, cells, and tissue using nanowire device arrays. IEEE Trans. Nanotechnol. 9, 269–280 (2010).

    Article  Google Scholar 

  114. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010).

    Article  CAS  Google Scholar 

  115. Miura, M. et al. Effect of nonuniform muscle contraction on sustainability and frequency of triggered arrhythmias in rat cardiac muscle. Circulation 121, 2711–2717 (2010).

    Article  CAS  Google Scholar 

  116. Liau, B., Zhang, D. & Bursac, N. Functional cardiac tissue engineering. Regen. Med. 7, 187–206 (2012).

    Article  CAS  Google Scholar 

  117. Tzatzalos, E., Abilez, O. J., Shukla, P. & Wu, J. C. Engineered heart tissues and induced pluripotent stem cells: macro-and microstructures for disease modeling, drug screening, and translational studies. Adv. Drug Delivery Rev. 96, 234–244 (2016).

    Article  CAS  Google Scholar 

  118. Burdick, J. A., Mauck, R. L., Gorman, J. H. & Gorman, R. C. Acellular biomaterials: an evolving alternative to cell-based therapies. Sci. Transl. Med. 5, 176ps4 (2013).

    Article  CAS  Google Scholar 

  119. Baker, B. M., Handorf, A. M., Ionescu, L. C., Li, W.-J. & Mauck, R. L. New directions in nanofibrous scaffolds for soft tissue engineering and regeneration. Expert Rev. Med. Devices 6, 515–532 (2009).

    Article  CAS  Google Scholar 

  120. Lee, J. W. 3D nanoprinting technologies for tissue engineering applications. J. Nanomater. 2015, 213521 (2015).

    Google Scholar 

  121. Serpooshan, V., Mahmoudi, M., Hu, D. A., Hu, J. B. & Wu, S. M. Bioengineering cardiac constructs using 3D printing. J. 3D Printing Med. 1, 123–139 (2017).

    Article  CAS  Google Scholar 

  122. Giannopoulos, A. A. et al. Applications of 3D printing in cardiovascular diseases. Nat. Rev. Cardiol. 13, 701–718 (2016).

    Article  CAS  Google Scholar 

  123. Dalton, P. D., Joergensen, N. T., Groll, J. & Moeller, M. Patterned melt electrospun substrates for tissue engineering. Biomed. Mater. 3, 034109 (2008).

    Article  CAS  Google Scholar 

  124. Chaudhury, K., Kumar, V., Kandasamy, J. & RoyChoudhury, S. Regenerative nanomedicine: current perspectives and future directions. Int. J. Nanomed. 9, 4153–4167 (2014).

    Article  Google Scholar 

  125. Kamaly, N., Xiao, Z., Valencia, P. M., Radovic-Moreno, A. F. & Farokhzad, O. C. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem. Soc. Rev. 41, 4153–4167 (2012).

    Article  CAS  Google Scholar 

  126. Behzadi, S. et al. Cellular uptake of nanoparticles: journey inside the cell. Chem. Soc. Rev. 46, 4218–4244 (2017).

    Article  CAS  Google Scholar 

  127. Bertrand, N. et al. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nat. Commun. (in the press).

  128. Mahmoudi, M. et al. Temperature: the “ignored” factor at the nanobio interface. ACS Nano 7, 6555–6562 (2013).

    Article  CAS  Google Scholar 

  129. Mahmoudi, M. et al. Variation of protein corona composition of gold nanoparticles following plasmonic heating. Nano Lett. 14, 6–12 (2014).

    Article  CAS  Google Scholar 

  130. Monopoli, M. P. et al. Physical−chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J. Am. Chem. Soc. 133, 2525–2534 (2011).

    Article  CAS  Google Scholar 

  131. Hajipour, M. J., Laurent, S., Aghaie, A., Rezaee, F. & Mahmoudi, M. Personalized protein coronas: a “key” factor at the nanobiointerface. Biomater. Sci. 2, 1210–1221 (2014).

    Article  CAS  Google Scholar 

  132. Corbo, C., Molinaro, R., Tabatabaei, M., Farokhzad, O. C. & Mahmoudi, M. Personalized protein corona on nanoparticles and its clinical implications. Biomater. Sci. 5, 378–387 (2017).

    Article  CAS  Google Scholar 

  133. Walkey, C. D. et al. Protein corona fingerprinting predicts the cellular interaction of gold and silver nanoparticles. ACS Nano 8, 2439–2455 (2014).

    Article  CAS  Google Scholar 

  134. Bigdeli, A. et al. Exploring cellular interactions of liposomes using protein corona fingerprints and physicochemical properties. ACS Nano 10, 3723–3737 (2016).

    Article  CAS  Google Scholar 

  135. Sharifi, S. et al. Toxicity of nanomaterials. Chem. Soc. Rev. 41, 2323–2343 (2012).

    Article  CAS  Google Scholar 

  136. Buzea, C., Pacheco, I. I. & Robbie, K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2, MR17–MR71 (2007).

    Article  Google Scholar 

  137. Bostan, H. B. et al. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Life Sci. 165, 91–99 (2016).

    Article  CAS  Google Scholar 

  138. Fleischer, S., Feiner, R. & Dvir, T. Cutting-edge platforms in cardiac tissue engineering. Curr. Opin. Biotechnol. 47, 23–29 (2017).

    Article  CAS  Google Scholar 

  139. Hrkach, J. et al. Cardiotoxicity of nano-particles. Sci. Transl. Med. 4, 128ra139 (2012).

    Article  Google Scholar 

  140. Gu, F. et al. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc. Natl Acad. Sci. USA 105, 2586–2591 (2008).

    Article  CAS  Google Scholar 

  141. Kim, Y. et al. Mass production and size control of lipid–polymer hybrid nanoparticles through controlled microvortices. Nano Lett. 12, 3587–3591 (2012).

    Article  CAS  Google Scholar 

  142. Xu, J. et al. Future of the particle replication in nonwetting templates (PRINT) technology. Angew. Chem. Int. Ed. 52, 6580–6589 (2013).

    Article  CAS  Google Scholar 

  143. Hajipour, M. J. et al. Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide. Nanoscale 7, 8978–8994 (2015).

    Article  CAS  Google Scholar 

  144. Smith, A. S. T., Macadangdang, J., Leung, W., Laflamme, M. A. & Kim, D.-H. Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening. Biotechnol. Adv. 35, 77–94 (2017).

    Article  CAS  Google Scholar 

  145. Tenzer, S. et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotech. 8, 772–781 (2013).

    Article  CAS  Google Scholar 

  146. Pozzi, D. et al. The biomolecular corona of nanoparticles in circulating biological media. Nanoscale 7, 13958–13966 (2015).

    Article  CAS  Google Scholar 

  147. Ott, H. C. et al. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).

    Article  CAS  Google Scholar 

  148. Tian, B. et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nat. Mater. 11, 986–994 (2012).

    Article  CAS  Google Scholar 

  149. Sooppan, R. et al. In vivo anastomosis and perfusion of a three-dimensionally-printed construct containing microchannel networks. Tissue Eng. Part C Methods 22, 1–7 (2015).

    Article  CAS  Google Scholar 

  150. Murphy, S. V. & Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773–785 (2014).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the US National Institutes of Health grants HL127464-01A1 (O.C.F.), EB015419 (O.C.F.) and HL133272 (J.C.W.), and Department of Defense grant PC140318 (O.C.F.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Morteza Mahmoudi or Omid C. Farokhzad.

Ethics declarations

Competing interests

R.L. and O.C.F. declare financial interests in Selecta Biosciences, Tarveda Therapeutics and Placon Therapeutics. R.L. declares financial interests in Moderna.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahmoudi, M., Yu, M., Serpooshan, V. et al. Multiscale technologies for treatment of ischemic cardiomyopathy. Nature Nanotech 12, 845–855 (2017). https://doi.org/10.1038/nnano.2017.167

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2017.167

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing