Annals of Biomedical Engineering

, Volume 44, Issue 3, pp 750–772 | Cite as

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

  • Daniela Y. Santiesteban
  • Kelsey Kubelick
  • Kabir S. Dhada
  • Diego Dumani
  • Laura SuggsEmail author
  • Stanislav EmelianovEmail author
Nondestructive Characterization of Biomaterials for Tissue Engineering and Drug Delivery


The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.


Regenerative medicine Imaging contrast agents Therapeutic agents Multimodal tracking In vivo imaging In vivo tracking Stem cells Scaffold engineering Real-time imaging 



Acoustic droplet vaporization


Alkaline phosphatase


Gold nanocage


Gold nanoparticle


Gold nanorod


Gold nanosphere


Blood-brain barrier


Basic fibroblast growth factors


Carbon nanotubes


Computed tomography


Cetyltrimethylammonium bromide


Growth factor


Gold nanobeacon


Hydroxypropyltrimethyl ammonium chloride chitosan




Indocyanine green


Iron oxide nanoparticles




Monitoring/Imaging and Regenerative Agents


Magnetic resonance imaging


Mesenchymal stem cell


Mesoporous silica nanoparticle


Multiple-wall carbon nanotube




Near infrared


Nitric oxide




Plasmid DNA


Polyethylene glycol




Positron emission tomography




Perfluorocarbon particle




Polyvinyl alcohol


Stem cell


Solid silica nanoparticle


Superparamagnetic iron oxide nanoparticles


Surface plasmon resonance


Single-walled carbon nanotube


Tissue engineering and regenerative medicine




Vascular cell adhesion molecule 1


Vascular endothelial growth factor


Vascular endothelial growth factor receptor


  1. 1.
    Alkilany, A. M., P. K. Nagaria, C. R. Hexel, T. J. Shaw, C. J. Murphy, and M. D. Wyatt. Cellular uptake and cytotoxicity of gold nanorods: Molecular origin of cytotoxicity and surface effects. Small 5:701–708, 2009.PubMedCrossRefGoogle Scholar
  2. 2.
    Ananta, J. S., M. L. Matson, A. M. Tang, T. Mandal, S. Lin, K. Wong, S. T. Wong, and L. J. Wilson. Single-walled carbon nanotube materials as T 2-weighted mri contrast agents. J. Phys. Chem. C 113:19369–19372, 2009.CrossRefGoogle Scholar
  3. 3.
    Andreas, K., R. Georgieva, M. Ladwig, S. Mueller, M. Notter, M. Sittinger, and J. Ringe. Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking. Biomaterials 33:4515–4525, 2012.PubMedCrossRefGoogle Scholar
  4. 4.
    Anwer, K., G. Kao, B. Proctor, I. Anscombe, V. Florack, R. Earls, E. Wilson, T. McCreery, E. Unger, and A. Rolland. Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration. Gene Ther. 7:1833–1839, 2000.PubMedCrossRefGoogle Scholar
  5. 5.
    Appel, A. A., M. A. Anastasio, J. C. Larson, and E. M. Brey. Imaging challenges in biomaterials and tissue engineering. Biomaterials 34:6615–6630, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Arriagada, F. J., and K. Osseo-Asare. Phase and dispersion stability effects in the synthesis of silica nanoparticles in a non-ionic reverse microemulsion. Colloids Surf. 69:105–115, 1992.CrossRefGoogle Scholar
  7. 7.
    Astolfo, A., F. Arfelli, E. Schültke, S. James, L. Mancini, and R.-H. Menk. A detailed study of gold-nanoparticle loaded cells using X-ray based techniques for cell-tracking applications with single-cell sensitivity. Nanoscale 5:3337–3345, 2013.PubMedCrossRefGoogle Scholar
  8. 8.
    Astolfo, A., E. Schültke, R. H. Menk, R. D. Kirch, B. H. J. Juurlink, C. Hall, L. A. Harsan, M. Stebel, D. Barbetta, G. Tromba, and F. Arfelli. In vivo visualization of gold-loaded cells in mice using X-ray computed tomography. Nanomed. Nanotechnol. Biol. Med. 9:284–292, 2013.CrossRefGoogle Scholar
  9. 9.
    Bae, K. H., Y. B. Kim, Y. Lee, J. Hwang, H. Park, and T. G. Park. Bioinspired synthesis and characterization of gadolinium-labeled magnetite nanoparticles for dual contrast T1-and T2-weighted magnetic resonance imaging. Bioconjug. Chem. 21:505–512, 2010.PubMedCrossRefGoogle Scholar
  10. 10.
    Bakhru, S. H., E. Altiok, C. Highley, D. Delubac, J. Suhan, T. K. Hitchens, C. Ho, and S. Zappe. Enhanced cellular uptake and long-term retention of chitosan-modified iron-oxide nanoparticles for MRI-based cell tracking. Int. J. Nanomed. 7:4613, 2012.CrossRefGoogle Scholar
  11. 11.
    Balakumaran, A., E. Pawelczyk, J. Ren, B. Sworder, A. Chaudhry, M. Sabatino, D. Stroncek, J. A. Frank, and P. G. Robey. Superparamagnetic iron oxide nanoparticles labeling of bone marrow stromal (mesenchymal) cells does not affect their “stemness”. PLoS ONE 5:e11462, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Barone, P. W., R. S. Parker, and M. S. Strano. In vivo fluorescence detection of glucose using a single-walled carbon nanotube optical sensor: design, fluorophore properties, advantages, and disadvantages. Anal. Chem. 77:7556–7562, 2005.PubMedCrossRefGoogle Scholar
  13. 13.
    Bartczak, D., O. L. Muskens, T. Sanchez-Elsner, A. G. Kanaras, and T. M. Millar. Manipulation of in vitro angiogenesis using peptide-coated gold nanoparticles. ACS Nano 7:5628–5636, 2013.PubMedCrossRefGoogle Scholar
  14. 14.
    Bauer, J., M. Zähres, A. Zellermann, M. Kirsch, F. Petrat, H. de Groot, and C. Mayer. Perfluorocarbon-filled poly (lactide-co-gylcolide) nano-and microcapsules as artificial oxygen carriers for blood substitutes: a physico-chemical assessment. J. Microencapsul. 27:122–132, 2010.PubMedCrossRefGoogle Scholar
  15. 15.
    Beck, Jr, G. R., S.-W. Ha, C. E. Camalier, M. Yamaguchi, Y. Li, J.-K. Lee, and M. N. Weitzmann. Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo. Nanomedicine 8:793–803, 2012.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Beck, J. S., J. C. Vartuli, W. J. Roth, M. E. Leonowicz, C. T. Kresge, K. D. Schmitt, C. T. W. Chu, D. H. Olson, and E. W. Sheppard. A new family of mesoporous molecular sieves prepared with liquid crystal templates. J. Am. Chem. Soc. 114:10834–10843, 1992.CrossRefGoogle Scholar
  17. 17.
    Benjamin, S., D. Sheyn, S. Ben-David, A. Oh, I. Kallai, N. Li, D. Gazit, and Z. Gazit. Oxygenated environment enhances both stem cell survival and osteogenic differentiation. Tissue Eng. Part A 19:748–758, 2013.PubMedCrossRefGoogle Scholar
  18. 18.
    Berthiaume, F., T. J. Maguire, and M. L. Yarmush. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu. Rev. Chem. Biomol. Eng. 2:403–430, 2011.PubMedCrossRefGoogle Scholar
  19. 19.
    Bock, N., A. Riminucci, C. Dionigi, A. Russo, A. Tampieri, E. Landi, V. A. Goranov, M. Marcacci, and V. Dediu. A novel route in bone tissue engineering: magnetic biomimetic scaffolds. Acta Biomater. 6:786–796, 2010.PubMedCrossRefGoogle Scholar
  20. 20.
    Bonoiu, A. C., S. D. Mahajan, H. Ding, I. Roy, K.-T. Yong, R. Kumar, R. Hu, E. J. Bergey, S. A. Schwartz, and P. N. Prasad. Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons. Proc. Natl. Acad. Sci. 106:5546–5550, 2009.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Bulte, J. W., and D. L. Kraitchman. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 17:484–499, 2004.PubMedCrossRefGoogle Scholar
  22. 22.
    Cai, X., B. S. Paratala, S. Hu, B. Sitharaman, and L. V. Wang. Multiscale photoacoustic microscopy of single-walled carbon nanotube-incorporated tissue engineering scaffolds. Tissue Eng. Part C Methods 18:310–317, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Cai, X., Y. Zhang, L. Li, S.-W. Choi, M. R. MacEwan, J. Yao, C. Kim, Y. Xia, and L. V. Wang. Investigation of neovascularization in three-dimensional porous scaffolds in vivo by a combination of multiscale photoacoustic microscopy and optical coherence tomography. Tissue Eng. Part C Methods 19:120907062030005–120907062030005, 2012.Google Scholar
  24. 24.
    Cai, X., S. Hu, B. Paratala, B. Sitharaman, and L. V. Wang. Dual-mode photoacoustic microscopy of carbon nanotube incorporated scaffolds in blood and biological tissues. In: SPIE BiOSInternational Society for Optics and Photonics, 2011, p. 789921–78996.Google Scholar
  25. 25.
    Cao, B., P. Qiu, and C. Mao. Mesoporous iron oxide nanoparticles prepared by polyacrylic acid etching and their application in gene delivery to mesenchymal stem cells. Microsc. Res. Tech. 76:936–941, 2013.PubMedCrossRefGoogle Scholar
  26. 26.
    Carenza, E., V. Barceló, A. Morancho, L. Levander, C. Boada, A. Laromaine, A. Roig, J. Montaner, and A. Rosell. In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies. Nanomed. Nanotechnol. Biol. Med. 10:225–234, 2014.CrossRefGoogle Scholar
  27. 27.
    Chan, M.-H., and H.-M. Lin. Preparation and identification of multifunctional mesoporous silica nanoparticles for in vitro and in vivo dual-mode imaging, theranostics, and targeted tracking. Biomaterials 46:149–158, 2015.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen, Y., K. Ai, J. Liu, G. Sun, Q. Yin, and L. Lu. Multifunctional envelope-type mesoporous silica nanoparticles for pH-responsive drug delivery and magnetic resonance imaging. Biomaterials 60:111–120, 2015.PubMedCrossRefGoogle Scholar
  29. 29.
    Chen, Y.-S., W. Frey, S. Kim, K. Homan, P. Kruizinga, K. Sokolov, and S. Emelianov. Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. Opt. Express 18:8867–8878, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Chithrani, B. D., and W. C. W. Chan. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 7:1542–1550, 2007.PubMedCrossRefGoogle Scholar
  31. 31.
    Choi, H. S., W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni. Renal clearance of quantum dots. Nat. Biotechnol. 25:1165–1170, 2007.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Chung, E., S. Y. Nam, L. M. Ricles, S. Y. Emelianov, and L. J. Suggs. Evaluation of gold nanotracers to track adipose-derived stem cells in a PEGylated fibrin gel for dermal tissue engineering applications. Int. J. Nanomed. 8:325–336, 2013.CrossRefGoogle Scholar
  33. 33.
    Chung, T.-H., S.-H. Wu, M. Yao, C.-W. Lu, Y.-S. Lin, Y. Hung, C.-Y. Mou, Y.-C. Chen, and D.-M. Huang. The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. Biomaterials 28:2959–2966, 2007.PubMedCrossRefGoogle Scholar
  34. 34.
    Cirillo, G., S. Hampel, U. G. Spizzirri, O. I. Parisi, N. Picci, and F. Iemma. Carbon nanotubes hybrid hydrogels in drug delivery: a perspective review. BioMed Res. Int. 2014:825017, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Cohen-karni, T., K. J. Jeong, J. H. Tsui, G. Reznor, M. Mustata, M. Wanunu, A. Graham, C. Marks, D. C. Bell, R. Langer, and D. S. Kohane. Nanocomposite gold-silk nano fibers. Nano Lett. 12:10–13, 2012.Google Scholar
  36. 36.
    Cook, J. R., W. Frey, and S. Emelianov. Quantitative photoacoustic imaging of nanoparticles in cells and tissues. ACS Nano 7:1272–1280, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Çukur, T., M. Yamada, W. R. Overall, P. Yang, and D. G. Nishimura. Positive contrast with alternating repetition time SSFP (PARTS): a fast imaging technique for SPIO-labeled cells. Magn. Reson. Med. 63:427–437, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Daniel, M.-C., and D. Astruc. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 104:293–346, 2004.PubMedCrossRefGoogle Scholar
  39. 39.
    De La Zerda, A., C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T.-J. Ma, and O. Oralkan. Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat. Nanotechnol. 3:557–562, 2008.PubMedCrossRefGoogle Scholar
  40. 40.
    de Rosales, R. T. M., R. Tavaré, A. Glaria, G. Varma, A. Protti, and P. J. Blower. 99mTc-bisphosphonate-iron oxide nanoparticle conjugates for dual-modality biomedical imaging. Bioconjug. Chem. 22:455–465, 2011.CrossRefGoogle Scholar
  41. 41.
    Delogu, L. G., G. Vidili, E. Venturelli, C. Ménard-Moyon, M. A. Zoroddu, G. Pilo, P. Nicolussi, C. Ligios, D. Bedognetti, and F. Sgarrella. Functionalized multiwalled carbon nanotubes as ultrasound contrast agents. Proc. Natl. Acad. Sci. 109:16612–16617, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Dobson, J. Gene therapy progress and prospects: magnetic nanoparticle-based gene delivery. Gene Ther. 13:283–287, 2006.PubMedCrossRefGoogle Scholar
  43. 43.
    Douglas, T. E., M. Pilarek, I. Kalaszczyńska, I. Senderek, A. Skwarczyńska, V. M. Cuijpers, Z. Modrzejewska, M. Lewandowska-Szumieł, and P. Dubruel. Enrichment of chitosan hydrogels with perfluorodecalin promotes gelation and stem cell vitality. Mater. Lett. 128:79–84, 2014.CrossRefGoogle Scholar
  44. 44.
    Dumortier, H., S. Lacotte, G. Pastorin, R. Marega, W. Wu, D. Bonifazi, J.-P. Briand, M. Prato, S. Muller, and A. Bianco. Functionalized carbon nanotubes are non-cytotoxic and preserve the functionality of primary immune cells. Nano Lett. 6:1522–1528, 2006.PubMedCrossRefGoogle Scholar
  45. 45.
    Duncanson, W. J., L. R. Arriaga, W. L. Ung, J. A. Kopechek, T. M. Porter, and D. A. Weitz. Microfluidic fabrication of perfluorohexane-shelled double emulsions for controlled loading and acoustic-triggered release of hydrophilic agents. Langmuir 30:13765–13770, 2014.PubMedCrossRefGoogle Scholar
  46. 46.
    Dvir, T., B. P. Timko, M. D. Brigham, S. R. Naik, S. S. Karajanagi, O. Levy, H. Jin, K. K. Parker, R. Langer, and D. S. Kohane. Nanowired three-dimensional cardiac patches. Nat. Nanotechnol. 6:720–725, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Erpelding, T. N., K. W. Hollman, and M. O’Donnell. Bubble-based acoustic radiation force elasticity imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 52:971–979, 2005.PubMedCrossRefGoogle Scholar
  48. 48.
    Fabiilli, M. L., C. G. Wilson, F. Padilla, F. M. Martín-Saavedra, J. B. Fowlkes, and R. T. Franceschi. Acoustic droplet-hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness. Acta Biomater. 9:7399–7409, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Fan, Z., R. E. Kumon, and C. X. Deng. Mechanisms of microbubble-facilitated sonoporation for drug and gene delivery. Ther. Deliv. 5:467, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Fan, D., Z. Yin, R. Cheong, F. Q. Zhu, R. C. Cammarata, C. L. Chien, and A. Levchenko. Subcellular-resolution delivery of a cytokine through precisely manipulated nanowires. Nat. Nanotechnol. 5:545–551, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Farini, A., C. Villa, A. Manescu, F. Fiori, A. Giuliani, P. Razini, C. Sitzia, G. Del Fraro, M. Belicchi, and M. Meregalli. Novel insight into stem cell trafficking in dystrophic muscles. Int. J. Nanomed. 7:3059, 2012.Google Scholar
  52. 52.
    Ganesh, N., R. Jayakumar, M. Koyakutty, U. Mony, and S. V. Nair. Embedded silica nanoparticles in poly(caprolactone) nanofibrous scaffolds enhanced osteogenic potential for bone tissue engineering. Tissue Eng. Part A 18:1867–1881, 2012.PubMedCrossRefGoogle Scholar
  53. 53.
    Garcia-Bennett, A. E., M. Kozhevnikova, N. Konig, C. Zhou, R. Leao, T. Knopfel, S. Pankratova, C. Trolle, V. Berezin, E. Bock, H. Aldskogius, and E. N. Kozlova. Delivery of differentiation factors by mesoporous silica particles assists advanced differentiation of transplanted murine embryonic stem cells. Stem Cells Transl Med 2:906–915, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Ghafar-Zadeh, E., J. R. Waldeisen, and L. P. Lee. Engineered approaches to the stem cell microenvironment for cardiac tissue regeneration. Lab Chip 11:3031–3048, 2011.PubMedCrossRefGoogle Scholar
  55. 55.
    Ghiazza, M. and G. Vietti. Carbon nanotubes: properties, applications and toxicity. In: Health and Environmental Safety of Nanomaterials. Torino: University of Torino, 2014.Google Scholar
  56. 56.
    Gong, H., R. Peng, and Z. Liu. Carbon nanotubes for biomedical imaging: the recent advances. Adv. Drug Deliv. Rev. 65:1951–1963, 2013.PubMedCrossRefGoogle Scholar
  57. 57.
    Grapentin, C., F. Mayenfels, S. Barnert, R. Süss, R. Schubert, S. Temme, C. Jacoby, J. Schrader, and U. Flögel. Optimization of perfluorocarbon nanoemulsions for molecular imaging by 19F MRI.Google Scholar
  58. 58.
    Green, D. E., J. P. Longtin, and B. Sitharaman. The effect of nanoparticle-enhanced photoacoustic stimulation on multipotent marrow stromal cells. ACS Nano 3:2065–2072, 2009.PubMedCrossRefGoogle Scholar
  59. 59.
    Guilak, F., D. M. Cohen, B. T. Estes, J. M. Gimble, W. Liedtke, and C. S. Chen. Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5:17–26, 2009.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Gupta, A. K., and M. Gupta. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021, 2005.PubMedCrossRefGoogle Scholar
  61. 61.
    Ha, S.-W., M. N. Weitzmann, and G. R. Beck. Bioactive silica nanoparticles promote osteoblast differentiation through stimulation of autophagy and direct association with LC3 and p62. ACS Nano 8:5898–5910, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Hainfeld, J. F., D. N. Slatkin, T. M. Focella, and H. M. Smilowitz. Gold nanoparticles: a new X-ray contrast agent. Br. J. Radiol. 79:248–253, 2006.PubMedCrossRefGoogle Scholar
  63. 63.
    Hannah, A., G. Luke, K. Wilson, K. Homan, and S. Emelianov. Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging. ACS Nano 8:250–259, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Hannah, A. S., D. VanderLaan, Y.-S. Chen, and S. Y. Emelianov. Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm. Biomed. Opt. Express 5:3042–3052, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Harrison, B. S., and A. Atala. Carbon nanotube applications for tissue engineering. Biomaterials 28:344–353, 2007.PubMedCrossRefGoogle Scholar
  66. 66.
    Hartono, S. B., N. T. Phuoc, M. Yu, Z. Jia, M. J. Monteiro, S. Qiao, and C. Yu. Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and co-delivery. J. Mater. Chem. B 2:718–726, 2014.CrossRefGoogle Scholar
  67. 67.
    Henkel-Hanke, T. Artificial oxygen carriers: a current review. AANA J 75:205, 2007.Google Scholar
  68. 68.
    Himes, N., J. Y. Min, R. Lee, C. Brown, J. Shea, X. Huang, Y. F. Xiao, J. P. Morgan, D. Burstein, and P. Oettgen. In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction. Magn. Reson. Med. 52:1214–1219, 2004.PubMedCrossRefGoogle Scholar
  69. 69.
    Hirsch, A. Functionalization of single-walled carbon nanotubes. Angew. Chem. Int. Ed. 41:1853–1859, 2002.CrossRefGoogle Scholar
  70. 70.
    Hoare, T., B. P. Timko, J. Santamaria, G. F. Goya, S. Irusta, S. Lau, C. F. Stefanescu, D. Lin, R. Langer, and D. S. Kohane. Magnetically triggered nanocomposite membranes: a versatile platform for triggered drug release. Nano Lett. 11:1395–1400, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Hong, G., J. C. Lee, J. T. Robinson, U. Raaz, L. Xie, N. F. Huang, J. P. Cooke, and H. Dai. Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat. Med. 18:1841–1846, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Huang, X., F. Zhang, H. Wang, G. Niu, K. Y. Choi, M. Swierczewska, G. Zhang, H. Gao, Z. Wang, L. Zhu, H. S. Choi, S. Lee, and X. Chen. Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery. Biomaterials 34:1772–1780, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Huber, D. L. Synthesis, properties, and applications of iron nanoparticles. Small 1:482–501, 2005.PubMedCrossRefGoogle Scholar
  74. 74.
    Iijima, S. Helical microtubules of graphitic carbon. Nature 354:56–58, 1991.CrossRefGoogle Scholar
  75. 75.
    Jackson, P. A., W. N. W. A. Rahman, C. J. Wong, T. Ackerly, and M. Geso. Potential dependent superiority of gold nanoparticles in comparison to iodinated contrast agents. Eur. J. Radiol. 75:104–109, 2010.PubMedCrossRefGoogle Scholar
  76. 76.
    Jacoby, C., S. Temme, F. Mayenfels, N. Benoit, M. P. Krafft, R. Schubert, J. Schrader, and U. Flögel. Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half-lives and sensitivity. NMR Biomed. 27:261–271, 2014.PubMedCrossRefGoogle Scholar
  77. 77.
    Jiang, S., A. A. Eltoukhy, K. T. Love, R. Langer, and D. G. Anderson. Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery. Nano Lett. 13:1059–1064, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Jin, Y., C. Jia, S.-W. Huang, M. O’Donnell, and X. Gao. Multifunctional nanoparticles as coupled contrast agents. Nat. Commun. 1:41, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Jin, Q., Z. Wang, F. Yan, Z. Deng, F. Ni, J. Wu, R. Shandas, X. Liu, and H. Zheng. A novel cationic microbubble coated with stearic acid-modified polyethylenimine to enhance DNA loading and gene delivery by ultrasound. PLoS ONE 8:e76544, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Jing, X.-H., L. Yang, X.-J. Duan, B. Xie, W. Chen, Z. Li, and H.-B. Tan. In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine 75:432–438, 2008.PubMedCrossRefGoogle Scholar
  81. 81.
    John, R., and S. A. Boppart. Magnetomotive molecular nanoprobes. Curr. Med. Chem. 18:2103, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Jokerst, J. V., C. Khademi, and S. S. Gambhir. Intracellular aggregation of multimodal silica nanoparticles for ultrasound-guided stem cell implantation. Sci. Transl. Med. 5:177ra135, 2013.CrossRefGoogle Scholar
  83. 83.
    Jokerst, J. V., M. Thangaraj, P. J. Kempen, R. Sinclair, and S. S. Gambhir. Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods. ACS Nano 6:5920–5930, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    José-Yacamán M., M. Miki-Yoshida, L. Rendon and J. Santiesteban. Catalytic growth of carbon microtubules with fullerene structure. Appl. Phys. Lett 62:202–204, 1993.CrossRefGoogle Scholar
  85. 85.
    Jung, C. W., and P. Jacobs. Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn. Reson. Imaging 13:661–674, 1995.PubMedCrossRefGoogle Scholar
  86. 86.
    Kam, N. W. S., M. O’Connell, J. A. Wisdom, and H. Dai. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc. Natl. Acad. Sci. USA 102:11600–11605, 2005.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Kemp, M. M., A. Kumar, S. Mousa, E. Dyskin, M. Yalcin, P. Ajayan, R. J. Linhardt, and S. A. Mousa. Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties. Nanotechnology 20:455104, 2009.PubMedCrossRefGoogle Scholar
  88. 88.
    Kempen, P. J., S. Greasley, K. A. Parker, J. L. Campbell, H.-Y. Chang, J. R. Jones, R. Sinclair, S. S. Gambhir, and J. V. Jokerst. Theranostic mesoporous silica nanoparticles biodegrade after pro-survival drug delivery and ultrasound/magnetic resonance imaging of stem cells. Theranostics 5:631–642, 2015.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Khandare, J. J., A. Jalota-Badhwar, S. D. Satavalekar, S. G. Bhansali, N. D. Aher, F. Kharas, and S. S. Banerjee. PEG-conjugated highly dispersive multifunctional magnetic multi-walled carbon nanotubes for cellular imaging. Nanoscale 4:837–844, 2012.PubMedCrossRefGoogle Scholar
  90. 90.
    Kievit, F. M., O. Veiseh, N. Bhattarai, C. Fang, J. W. Gunn, D. Lee, R. G. Ellenbogen, J. M. Olson, and M. Zhang. PEI–PEG–chitosan-copolymer-coated iron oxide nanoparticles for safe gene delivery: synthesis, complexation, and transfection. Adv. Funct. Mater. 19:2244–2251, 2009.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Kim, J.-W., E. I. Galanzha, E. V. Shashkov, H.-M. Moon, and V. P. Zharov. Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. Nat. Nanotechnol. 4:688–694, 2009.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Kim, J. H., M. H. Kim, D. H. Jo, Y. S. Yu, T. G. Lee, and J. H. Kim. The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation. Biomaterials 32:1865–1871, 2011.PubMedCrossRefGoogle Scholar
  93. 93.
    Klibanov, A. L. Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. Bioconjug. Chem. 16:9–17, 2005.PubMedCrossRefGoogle Scholar
  94. 94.
    Kokhuis, T., I. Skachkov, B. Naaijkens, L. Juffermans, O. Kamp, A. van der Steen, M. Versluis, and N. de Jong. StemBells: localized stem cell delivery using targeted microbubbles and acoustic radiation force. J. Acoust. Soc. Am. 135:2310–2310, 2014.Google Scholar
  95. 95.
    Kong, L., C. S. Alves, W. Hou, J. Qiu, H. Möhwald, H. Tomás, and X. Shi. RGD Peptide-Modified Dendrimer-Entrapped Gold Nanoparticles Enable Highly Efficient and Specific Gene Delivery to Stem Cells. ACS Appl. Mater. Interfaces 7:4833–4843, 2015.PubMedCrossRefGoogle Scholar
  96. 96.
    Korzeniowska, B., R. Nooney, D. Wencel, and C. McDonagh. Silica nanoparticles for cell imaging and intracellular sensing. Nanotechnology 24:442002, 2013.PubMedCrossRefGoogle Scholar
  97. 97.
    Kresge, C. T., M. E. Leonowicz, W. J. Roth, J. C. Vartuli, and J. S. Beck. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359:710–712, 1992.CrossRefGoogle Scholar
  98. 98.
    Lalwani, G., A. Gopalan, M. D’Agati, J. Srinivas Sankaran, S. Judex, Y. X. Qin, and B. Sitharaman. Porous three-dimensional carbon nanotube scaffolds for tissue engineering. J Biomed. Mater. Res. Part A 103:3212–3225, 2015.CrossRefGoogle Scholar
  99. 99.
    Laurent, S., D. Forge, M. Port, A. Roch, C. Robic, L. Vander Elst, and R. N. Muller. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108:2064–2110, 2008.PubMedCrossRefGoogle Scholar
  100. 100.
    Lee, H.-Y., H.-W. Kim, J. H. Lee, and S. H. Oh. Controlling oxygen release from hollow microparticles for prolonged cell survival under hypoxic environment. Biomaterials 53:583–591, 2015.PubMedCrossRefGoogle Scholar
  101. 101.
    Lee, J. H., J.-Y. Lee, S. H. Yang, E.-J. Lee, and H.-W. Kim. Carbon nanotube–collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors. Acta Biomater. 10:4425–4436, 2014.PubMedCrossRefGoogle Scholar
  102. 102.
    Lee, H.-Y., Z. Li, K. Chen, A. R. Hsu, C. Xu, J. Xie, S. Sun, and X. Chen. PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles. J. Nucl. Med. 49:1371–1379, 2008.PubMedCrossRefGoogle Scholar
  103. 103.
    Leu, J. G., S. A. Chen, H. M. Chen, W. M. Wu, C. F. Hung, Y. D. Yao, C. S. Tu, and Y. J. Liang. The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid. Nanomed. Nanotechnol. Biol. Med. 8:767–775, 2012.CrossRefGoogle Scholar
  104. 104.
    Levy, I., I. Sher, E. Corem-Salkmon, O. Ziv-Polat, A. Meir, A. J. Treves, A. Nagler, O. Kalter-Leibovici, S. Margel, and Y. Rotenstreich. Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation. J. Nanobiotechnol. 13:1–14, 2015.CrossRefGoogle Scholar
  105. 105.
    Lewandowska-Łańcucka, J., S. Fiejdasz, Ł. Rodzik, M. Kozieł, and M. Nowakowska. Bioactive hydrogel-nanosilica hybrid materials: a potential injectable scaffold for bone tissue engineering. Biomed. Mater. 10:015020, 2015.PubMedCrossRefGoogle Scholar
  106. 106.
    Li, Y., G. Huang, X. Zhang, B. Li, Y. Chen, T. Lu, T. J. Lu, and F. Xu. Magnetic hydrogels and their potential biomedical applications. Adv. Funct. Mater. 23:660–672, 2013.CrossRefGoogle Scholar
  107. 107.
    Li, X., H. Liu, X. Niu, B. Yu, Y. Fan, Q. Feng, F.-Z. Cui, and F. Watari. The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo. Biomaterials 33:4818–4827, 2012.PubMedCrossRefGoogle Scholar
  108. 108.
    Liu, Z., C. Davis, W. Cai, L. He, X. Chen, and H. Dai. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc. Natl. Acad. Sci. 105:1410–1415, 2008.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Liu, G., R. Hong, L. Guo, Y. Li, and H. Li. Preparation, characterization and MRI application of carboxymethyl dextran coated magnetic nanoparticles. Appl. Surf. Sci. 257:6711–6717, 2011.CrossRefGoogle Scholar
  110. 110.
    Liu, Z., X. Li, S. M. Tabakman, K. Jiang, S. Fan, and H. Dai. Multiplexed multicolor Raman imaging of live cells with isotopically modified single walled carbon nanotubes. J. Am. Chem. Soc. 130:13540–13541, 2008.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Liu, D., C. Yi, D. Zhang, J. Zhang, and M. Yang. Inhibition of proliferation and differentiation of mesenchymal stem cells by carboxylated carbon nanotubes. ACS Nano 4:2185–2195, 2010.PubMedCrossRefGoogle Scholar
  112. 112.
    Ma, N., H. Cheng, M. Lu, Q. Liu, X. Chen, G. Yin, H. Zhu, L. Zhang, X. Meng, and Y. Tang. Magnetic resonance imaging with superparamagnetic iron oxide fails to track the long-term fate of mesenchymal stem cells transplanted into heart. Sci. Rep. 5:9058, 2015.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Mahmoudi, M., A. Simchi, M. Imani, A. S. Milani, and P. Stroeve. Optimal design and characterization of superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol for targeted delivery and imaging. J. Phys. Chem. B 112:14470–14481, 2008.PubMedCrossRefGoogle Scholar
  114. 114.
    Main, M. L., and P. A. Grayburn. Clinical applications of transpulmonary contrast echocardiography. Am. Heart J. 137:144–153, 1999.PubMedCrossRefGoogle Scholar
  115. 115.
    Mehrmohammadi, M., T.-H. Shin, M. Qu, P. Kruizinga, R. L. Truby, J.-H. Lee, J. Cheon, and S. Y. Emelianov. In vivo pulsed magneto-motive ultrasound imaging using high-performance magnetoactive contrast nanoagents. Nanoscale 5:11179–11186, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Menk, R. H., E. Schültke, C. Hall, F. Arfelli, A. Astolfo, L. Rigon, A. Round, K. Ataelmannan, S. R. MacDonald, and B. H. J. Juurlink. Gold nanoparticle labeling of cells is a sensitive method to investigate cell distribution and migration in animal models of human disease. Nanomed. Nanotechnol. Biol. Med. 7:647–654, 2011.CrossRefGoogle Scholar
  117. 117.
    Mikael, P. E., A. R. Amini, J. Basu, M. J. Arellano-Jimenez, C. T. Laurencin, M. M. Sanders, C. B. Carter, and S. P. Nukavarapu. Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication, in vitro and in vivo evaluation. Biomed. Mater. 9:035001, 2014.PubMedCrossRefGoogle Scholar
  118. 118.
    Mok, H., and M. Zhang. Superparamagnetic iron oxide nanoparticle-based delivery systems for biotherapeutics. Expert Opin. Drug Deliv. 10:73–87, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Moncion, A., O. D. Kripfgans, P. L. Carson, J. B. Fowlkes, and M. L. Fabiilli. Characterization of acoustic droplet vaporization and inertial cavitation thresholds in acoustically-responsive tissue scaffolds. In: In Ultrasonics Symposium, 2014.Google Scholar
  120. 120.
    Moon, G. D., S.-W. Choi, X. Cai, W. Li, E. C. Cho, and U. Jeong. A new theranostic system based on gold nanocages and phase-change materials with unique features for photoacoustic imaging and controlled release. JACS 133:4762–4765, 2011.CrossRefGoogle Scholar
  121. 121.
    Mooney, E., P. Dockery, U. Greiser, M. Murphy, and V. Barron. Carbon nanotubes and mesenchymal stem cells: biocompatibility, proliferation and differentiation. Nano Lett. 8:2137–2143, 2008.PubMedCrossRefGoogle Scholar
  122. 122.
    Mooney, E., J. N. Mackle, D. J.-P. Blond, E. O’Cearbhaill, G. Shaw, W. J. Blau, F. P. Barry, V. Barron, and J. M. Murphy. The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs. Biomaterials 33:6132–6139, 2012.PubMedCrossRefGoogle Scholar
  123. 123.
    Moradian, H., H. Fasehee, H. Keshvari, and S. Faghihi. Poly (ethyleneimine) functionalized carbon nanotubes as efficient nano-vector for transfecting mesenchymal stem cells. Colloids Surf. B 122:115–125, 2014.CrossRefGoogle Scholar
  124. 124.
    Mukherjee, P., R. Bhattacharya, P. Wang, L. Wang, S. Basu, J. A. Nagy, A. Atala, D. Mukhopadhyay, and S. Soker. Antiangiogenic properties of gold nanoparticles. Clin. Cancer Res. 11:3530–3534, 2005.PubMedCrossRefGoogle Scholar
  125. 125.
    Muroski, M. E., T. J. Morgan, C. W. Levenson, and F. Strouse. A gold nanoparticle pentapeptide: gene fusion to induce therapeutic gene expression in mesenchymal stem cells. J. Am. Chem. Soc. 136:14763–14771, 2014.PubMedCrossRefGoogle Scholar
  126. 126.
    Nam, S. Y., L. M. Ricles, L. J. Suggs, and S. Y. Emelianov. In vivo ultrasound and photoacoustic monitoring of mesenchymal stem cells labeled with gold nanotracers. PLoS ONE 7:1–9, 2012.Google Scholar
  127. 127.
    Nam, S. Y., L. M. Ricles, L. J. Suggs, and S. Y. Emelianov. Imaging strategies for tissue engineering applications. Tissue Eng. Part B 21:88–102, 2014.CrossRefGoogle Scholar
  128. 128.
    Ohgushi, M., K. Nagayama, and A. Wada. Dextran-magnetite: a new relaxation reagent and its application to T 2 measurements in gel systems. J. Magn. Reson. 29:599–601, 1978.Google Scholar
  129. 129.
    Oldenburg, A., F. Toublan, K. Suslick, A. Wei, and S. Boppart. Magnetomotive contrast for in vivo optical coherence tomography. Opt. Express 13:6597–6614, 2005.PubMedCrossRefGoogle Scholar
  130. 130.
    Olsson, M. B., B. R. Persson, L. G. Salford, and U. Schröder. Ferromagnetic particles as contrast agent in T2 NMR imaging. Magn. Reson. Imaging 4:437–440, 1986.CrossRefGoogle Scholar
  131. 131.
    Orza, A., O. Soritau, L. Olenic, M. Diudea, A. Florea, D. Rus Ciuca, C. Mihu, D. Casciano, and A. S. Biris. Electrically conductive gold-coated collagen nanofibers for placental-derived mesenchymal stem cells enhanced differentiation and proliferation. ACS Nano 5:4490–4503, 2011.PubMedCrossRefGoogle Scholar
  132. 132.
    Otani, K., K. Yamahara, S. Ohnishi, H. Obata, S. Kitamura, and N. Nagaya. Nonviral delivery of siRNA into mesenchymal stem cells by a combination of ultrasound and microbubbles. J. Control. Release 133:146–153, 2009.PubMedCrossRefGoogle Scholar
  133. 133.
    O’connell, M. J. Carbon Nanotubes: Properties and Applications. Boca Raton: CRC Press, 2006.CrossRefGoogle Scholar
  134. 134.
    Pan, L., Q. He, J. Liu, Y. Chen, M. Ma, L. Zhang, and J. Shi. Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J. Am. Chem. Soc. 134:5722–5725, 2012.PubMedCrossRefGoogle Scholar
  135. 135.
    Pan, D., M. Pramanik, A. Senpan, J. S. Allen, H. Zhang, S. A. Wickline, L. V. Wang, and G. M. Lanza. Molecular photoacoustic imaging of angiogenesis with integrin-targeted gold nanobeacons. FASEB J. 25:875–882, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Panje, C. M., D. S. Wang, M. A. Pysz, R. Paulmurugan, Y. Ren, F. Tranquart, L. Tian, and J. K. Willmann. Ultrasound-mediated gene delivery with cationic versus neutral microbubbles: effect of DNA and microbubble dose on in vivo transfection efficiency. Theranostics 2:1078, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Park, J. W., S. H. Ku, H. H. Moon, M. Lee, D. Choi, J. Yang, Y. M. Huh, J. H. Jeong, T. G. Park, and H. Mok. Cross-linked iron oxide nanoparticles for therapeutic engineering and in vivo monitoring of mesenchymal stem cells in cerebral ischemia model. Macromol. Biosci. 14:380–389, 2014.PubMedCrossRefGoogle Scholar
  138. 138.
    Park, W., H. N. Yang, D. Ling, H. Yim, K. S. Kim, T. Hyeon, K. Na, and K.-H. Park. Multi-modal transfection agent based on monodisperse magnetic nanoparticles for stem cell gene delivery and tracking. Biomaterials 35:7239–7247, 2014.PubMedCrossRefGoogle Scholar
  139. 139.
    Pastine, S. J., D. Okawa, A. Zettl, and J. M. Fréchet. Chemicals on demand with phototriggerable microcapsules. J. Am. Chem. Soc. 131:13586–13587, 2009.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Patlolla, A., B. Knighten, and P. Tchounwou. Multi-walled carbon nanotubes induce cytotoxicity, genotoxicity and apoptosis in normal human dermal fibroblast cells. Ethn. Dis. 20:S1, 2010.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Phillips, E., O. Penate-Medina, P. B. Zanzonico, R. D. Carvajal, P. Mohan, Y. Ye, J. Humm, M. Gönen, H. Kalaigian, H. Schöder, H. W. Strauss, S. M. Larson, U. Wiesner, and M. S. Bradbury. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med. 6:260, 2014.CrossRefGoogle Scholar
  142. 142.
    Plank, C., O. Zelphati, and O. Mykhaylyk. Magnetically enhanced nucleic acid delivery. Ten years of magnetofection—Progress and prospects. Adv. Drug Deliv. Rev. 63:1300–1331, 2011.PubMedCrossRefGoogle Scholar
  143. 143.
    Pochon, S., I. Tardy, P. Bussat, T. Bettinger, J. Brochot, M. von Wronski, L. Passantino, and M. Schneider. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest. Radiol. 45:89–95, 2010.PubMedCrossRefGoogle Scholar
  144. 144.
    Poologasundarampillai, G., B. Yu, O. Tsigkou, E. Valliant, S. Yue, P. D. Lee, R. W. Hamilton, M. M. Stevens, T. Kasuga, and J. R. Jones. Bioactive silica-poly(γ-glutamic acid) hybrids for bone regeneration: effect of covalent coupling on dissolution and mechanical properties and fabrication of porous scaffolds. Soft Matter 8:4822–4832, 2012.CrossRefGoogle Scholar
  145. 145.
    Prato, M., K. Kostarelos, and A. Bianco. Functionalized carbon nanotubes in drug design and discovery. Acc. Chem. Res. 41:60–68, 2007.PubMedCrossRefGoogle Scholar
  146. 146.
    Richard, C., B.-T. Doan, J.-C. Beloeil, M. Bessodes, É. Tóth, and D. Scherman. Noncovalent functionalization of carbon nanotubes with amphiphilic Gd3+ chelates: toward powerful T 1 and T 2 MRI contrast agents. Nano Lett. 8:232–236, 2008.PubMedCrossRefGoogle Scholar
  147. 147.
    Ricles, L. M., S. Y. Nam, K. Sokolov, S. Y. Emelianov, and L. J. Suggs. Function of mesenchymal stem cells following loading of gold nanotracers. Int. J. Nanomed. 6:407–416, 2011.CrossRefGoogle Scholar
  148. 148.
    Ricles, L. M., S. Y. Nam, E. A. Treviño, S. Y. Emelianov, and L. J. Suggs. A dual gold nanoparticle system for mesenchymal stem cell tracking. J. Mater. Chem. B 2:8220–8230, 2014.CrossRefGoogle Scholar
  149. 149.
    Riegler, J., A. Liew, S. O. Hynes, D. Ortega, T. O’Brien, R. M. Day, T. Richards, F. Sharif, Q. A. Pankhurst, and M. F. Lythgoe. Superparamagnetic iron oxide nanoparticle targeting of MSCs in vascular injury. Biomaterials 34:1987–1994, 2013.PubMedCrossRefGoogle Scholar
  150. 150.
    Riess, J. G. Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif. Cells Blood Substit. Biotechnol. 33:47–63, 2005.CrossRefGoogle Scholar
  151. 151.
    Ruiz-Cabello, J., B. P. Barnett, P. A. Bottomley, and J. W. Bulte. Fluorine (19F) MRS and MRI in biomedicine. NMR Biomed. 24:114–129, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Scapin, G., P. Salice, S. Tescari, E. Menna, V. De Filippis, and F. Filippini. Enhanced neuronal cell differentiation combining biomimetic peptides and a carbon nanotube-polymer scaffold. Nanomed. Nanotechnol. Biol. Med. 11:621–632, 2015.CrossRefGoogle Scholar
  153. 153.
    Schöni, D. S., S. Bogni, A. Bregy, A. Wirth, A. Raabe, I. Vajtai, U. Pieles, M. Reinert, and M. Frenz. Nanoshell assisted laser soldering of vascular tissue. Lasers Surg. Med. 43:975–983, 2011.PubMedCrossRefGoogle Scholar
  154. 154.
    Sheeran, P. S., S. Luois, P. A. Dayton, and T. O. Matsunaga. Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. Langmuir 27:10412–10420, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Siefker, J., P. Karande, and M.-O. Coppens. Packaging biological cargoes in mesoporous materials: opportunities for drug delivery. Expert Opin. Drug Deliv. 11:1781–1793, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Singh, M. K., J. Gracio, P. LeDuc, P. P. Gonçalves, P. A. Marques, G. Gonçalves, F. Marques, V. S. Silva, F. C. E. Silva, and J. Reis. Integrated biomimetic carbon nanotube composites for in vivo systems. Nanoscale 2:2855–2863, 2010.PubMedCrossRefGoogle Scholar
  157. 157.
    Siqueira, I. A. B., M. A. Corat, B. D. N. Cavalcanti, W. A. R. Neto, A. A. Martin, R. E. S. Bretas, F. R. Marciano, and A. O. Lobo. In vitro and in vivo studies of a novel poly (d, l-lactic acid), superhydrophilic carbon nanotubes and nanohydroxyapatite scaffolds for bone regeneration. ACS Appl. Mater. Interfaces 2015.Google Scholar
  158. 158.
    Skrabalak, S. E., J. Chen, Y. Sun, X. Lu, L. Au, C. M. Cobley, and Y. Xia. Gold nanocages: synthesis, properties, and applications. Acc. Chem. Res. 41:1587–1595, 2008.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Slowing, I. I., B. G. Trewyn, and V. S. Y. Lin. Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins. J. Am. Chem. Soc. 129:8845–8849, 2007.PubMedCrossRefGoogle Scholar
  160. 160.
    Slowing, I. I., J. L. Vivero-Escoto, B. G. Trewyn, and V. S. Y. Lin. Mesoporous silica nanoparticles: structural design and applications. J. Mater. Chem. 20:7924–7937, 2010.CrossRefGoogle Scholar
  161. 161.
    Stephen, Z. R., F. M. Kievit, and M. Zhang. Magnetite nanoparticles for medical MR imaging. Mater. Today 14:330–338, 2011.CrossRefGoogle Scholar
  162. 162.
    Stöber, W., A. Fink, and E. Bohn. Controlled growth of monodisperse silica spheres in the micron size range. J. Colloid Interface Sci. 26:62–69, 1968.CrossRefGoogle Scholar
  163. 163.
    Suh, J. S., J. Y. Lee, Y. S. Choi, F. Yu, V. Yang, S. J. Lee, C. P. Chung, and Y. J. Park. Efficient labeling of mesenchymal stem cells using cell permeable magnetic nanoparticles. Biochem. Biophys. Res. Commun. 379:669–675, 2009.PubMedCrossRefGoogle Scholar
  164. 164.
    Sun, Z., V. Yathindranath, M. Worden, J. A. Thliveris, S. Chu, F. E. Parkinson, T. Hegmann, and D. W. Miller. Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models. Int. J. Nanomed. 8:961, 2013.CrossRefGoogle Scholar
  165. 165.
    Sutton, J., J. Raymond, M. Verleye, G. Pyne-Geithman, and C. Holland. Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue. Int. J. Nanomed. 9:4671, 2014.CrossRefGoogle Scholar
  166. 166.
    Sykova, E., and P. Jendelova. Migration, fate and in vivo imaging of adult stem cells in the CNS. Cell Death Differ. 14:1336–1342, 2007.PubMedCrossRefGoogle Scholar
  167. 167.
    Talaie, T., S. J. Pratt, C. Vanegas, S. Xu, R. F. Henn, P. Yarowsky, and R. M. Lovering. Site-specific targeting of platelet-rich plasma via superparamagnetic nanoparticles. Orthop. J. Sports Med. 3:2325967114566185, 2015.PubMedCentralCrossRefGoogle Scholar
  168. 168.
    Talukdar, Y., P. Avti, J. Sun, and B. Sitharaman. Multimodal ultrasound-photoacoustic imaging of tissue engineering scaffolds and blood oxygen saturation in and around the scaffolds. Tissue Eng. Part C Methods 20:440–449, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Tan, B., and S. E. Rankin. Dual latex/surfactant templating of hollow spherical silica particles with ordered mesoporous shells. Langmuir 21:8180–8187, 2005.PubMedCrossRefGoogle Scholar
  170. 170.
    Tang, S., Y. Tang, L. Zhong, K. Murat, G. Asan, J. Yu, R. Jian, C. Wang, and P. Zhou. Short-and long-term toxicities of multi-walled carbon nanotubes in vivo and in vitro. J. Appl. Toxicol. 32:900–912, 2012.PubMedCrossRefGoogle Scholar
  171. 171.
    Tarn, D., C. E. Ashley, M. Xue, E. C. Carnes, J. I. Zink, and C. J. Brinker. Mesoporous silica nanoparticle nanocarriers: biofunctionality and biocompatibility. Acc. Chem. Res. 46:792–801, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Tavri, S., A. Vezeridis, W. Cui, and R. F. Mattrey. In vivo transfection and detection of gene expression of stem cells preloaded with DNA-carrying microbubbles. Radiology 276:518–525, 2015.PubMedCrossRefGoogle Scholar
  173. 173.
    Terrovitis, J., M. Stuber, A. Youssef, S. Preece, M. Leppo, E. Kizana, M. Schär, G. Gerstenblith, R. G. Weiss, and E. Marbán. Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation 117:1555–1562, 2008.PubMedCrossRefGoogle Scholar
  174. 174.
    Tinkov, S., R. Bekeredjian, G. Winter, and C. Coester. Microbubbles as ultrasound triggered drug carriers. J. Pharm. Sci. 98:1935–1961, 2009.PubMedCrossRefGoogle Scholar
  175. 175.
    Tran, P. A., L. Zhang, and T. J. Webster. Carbon nanofibers and carbon nanotubes in regenerative medicine. Adv. Drug Deliv. Rev. 61:1097–1114, 2009.PubMedCrossRefGoogle Scholar
  176. 176.
    Trewyn, B. G., I. I. Slowing, S. Giri, H.-T. Chen, and V. S. Y. Lin. Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol–gel process and applications in controlled release. Acc. Chem. Res. 40:846–853, 2007.PubMedCrossRefGoogle Scholar
  177. 177.
    Ulissi, Z. W., F. Sen, X. Gong, S. Sen, N. Iverson, A. A. Boghossian, L. C. Godoy, G. N. Wogan, D. Mukhopadhyay, and M. S. Strano. Spatiotemporal intracellular nitric oxide signaling captured using internalized, near-infrared fluorescent carbon nanotube nanosensors. Nano Lett. 14:4887–4894, 2014.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Unger, E., T. Porter, J. Lindner, and P. Grayburn. Cardiovascular drug delivery with ultrasound and microbubbles. Adv. Drug Deliv. Rev. 72:110–126, 2014.PubMedCrossRefGoogle Scholar
  179. 179.
    Varner, V. D., and C. M. Nelson. Toward the directed self-assembly of engineered tissues. Annu. Rev. Chem. Biomol. Eng. 5:507–526, 2014.PubMedCrossRefGoogle Scholar
  180. 180.
    Vashist, S. K., D. Zheng, G. Pastorin, K. Al-Rubeaan, J. H. Luong, and F.-S. Sheu. Delivery of drugs and biomolecules using carbon nanotubes. Carbon 49:4077–4097, 2011.CrossRefGoogle Scholar
  181. 181.
    Villa, C., S. Erratico, P. Razini, F. Fiori, F. Rustichelli, Y. Torrente, and M. Belicchi. Stem cell tracking by nanotechnologies. Int. J. Mol. Sci. 11:1070–1081, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Vittorio, O., S. L. Duce, A. Pietrabissa, and A. Cuschieri. Multiwall carbon nanotubes as MRI contrast agents for tracking stem cells. Nanotechnology 22:095706, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Vivero-Escoto, J. L., R. C. Huxford-Phillips, and W. Lin. Silica-based nanoprobes for biomedical imaging and theranostic applications. Chem. Soc. Rev. 41:2673–2685, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Wahajuddin, S. A. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int. J. Nanomed. 7:3445, 2012.CrossRefGoogle Scholar
  185. 185.
    Wang, Y.-X. J., S. M. Hussain, and G. P. Krestin. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur. Radiol. 11:2319–2331, 2001.PubMedCrossRefGoogle Scholar
  186. 186.
    Wang, C., X. Ma, S. Ye, L. Cheng, K. Yang, L. Guo, C. Li, Y. Li, and Z. Liu. Protamine functionalized single-walled carbon nanotubes for stem cell labeling and in vivo Raman/magnetic resonance/photoacoustic triple-modal imaging. Adv. Funct. Mater. 22:2363–2375, 2012.CrossRefGoogle Scholar
  187. 187.
    Weissleder, R. A., D. Stark, B. Engelstad, B. Bacon, C. Compton, D. White, P. Jacobs, and J. Lewis. Superparamagnetic iron oxide: pharmacokinetics and toxicity. Am. J. Roentgenol. 152:167–173, 1989.CrossRefGoogle Scholar
  188. 188.
    Wick, P., P. Manser, L. K. Limbach, U. Dettlaff-Weglikowska, F. Krumeich, S. Roth, W. J. Stark, and A. Bruinink. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol. Lett. 168:121–131, 2007.PubMedCrossRefGoogle Scholar
  189. 189.
    Widder, K. J., A. E. Senyei, and D. G. Scarpelli. Magnetic microspheres: a model system for site specific drug delivery in vivo. Exp. Biol. Med. 158:141–146, 1978.CrossRefGoogle Scholar
  190. 190.
    Wilson, K., K. Homan, and S. Emelianov. Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging. Nat. Commun. 3:618, 2012.PubMedCrossRefGoogle Scholar
  191. 191.
    Wu, H., H. Shi, H. Zhang, X. Wang, Y. Yang, C. Yu, C. Hao, J. Du, H. Hu, and S. Yang. Prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery. Biomaterials 35:5369–5380, 2014.PubMedCrossRefGoogle Scholar
  192. 192.
    Xie, J., S. Lee, and X. Chen. Nanoparticle-based theranostic agents. Adv. Drug Deliv. Rev. 62:1064–1079, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Xie, J., C. Xu, N. Kohler, Y. Hou, and S. Sun. Controlled PEGylation of monodisperse Fe3O4 nanoparticles for reduced non-specific uptake by macrophage cells. Adv. Mater. 19:3163–3166, 2007.CrossRefGoogle Scholar
  194. 194.
    Xu, Y.-L., Y.-H. Gao, Z. Liu, K.-B. Tan, X. Hua, Z.-Q. Fang, Y.-L. Wang, Y.-J. Wang, H.-M. Xia, and Z.-X. Zhuo. Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic ultrasound-mediated microbubble destruction improves cardiac function in myocardial infarction of New Zealand rabbits. Int. J. Cardiol. 138:182–195, 2010.PubMedCrossRefGoogle Scholar
  195. 195.
    Yanagi, T., H. Kajiya, M. Kawaguchi, H. Kido, and T. Fukushima. Photothermal stress triggered by near infrared-irradiated carbon nanotubes promotes bone deposition in rat calvarial defects. J. Biomater. Appl. 29:1109–1118, 2015.PubMedCrossRefGoogle Scholar
  196. 196.
    Yang, N., X. Chen, T. Ren, P. Zhang, and D. Yang. Carbon nanotube based biosensors. Sens Actuators B Chem 207:690–715, 2015.CrossRefGoogle Scholar
  197. 197.
    Yang, W., P. Thordarson, J. J. Gooding, S. P. Ringer, and F. Braet. Carbon nanotubes for biological and biomedical applications. Nanotechnology 18:412001, 2007.CrossRefGoogle Scholar
  198. 198.
    Yi, C., D. Liu, C.-C. Fong, J. Zhang, and M. Yang. Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 4:6439–6448, 2010.PubMedCrossRefGoogle Scholar
  199. 199.
    Yoon, S., S. Aglyamov, A. Karpiouk, and S. Emelianov. A high pulse repetition frequency ultrasound system for the ex vivo measurement of mechanical properties of crystalline lenses with laser-induced microbubbles interrogated by acoustic radiation force. Phys. Med. Biol. 57:4871, 2012.PubMedPubMedCentralCrossRefGoogle Scholar
  200. 200.
    Yoon, S. J., S. Mallidi, J. M. Tam, J. O. Tam, A. Murthy, P. Joshi, K. P. Johnston, K. V. Sokolov, and S. Y. Emelianov. Biodegradable plasmonic nanoclusters as contrast agent for photoacoustic imaging. In: Proceedings of SPIE, 2010.Google Scholar
  201. 201.
    You, J. O., M. Rafat, G. J. C. Ye, and D. T. Auguste. Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression. Nano Lett. 11:3643–3648, 2011.PubMedCrossRefGoogle Scholar
  202. 202.
    Zang, R., and S.-T. Yang. Multiwalled carbon nanotube-coated polyethylene terephthalate fibrous matrices for enhanced neuronal differentiation of mouse embryonic stem cells. J. Mater. Chem. B 1:646–653, 2013.CrossRefGoogle Scholar
  203. 203.
    Zerda, A. D. L., Z. Liu, S. Bodapati, R. Teed, S. Vaithilingam, B. T. Khuri-Yakub, X. Chen, H. Dai, and S. S. Gambhir. Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice. Nano Lett. 10:2168–2172, 2010.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Zhang, Y. S., Y. Wang, L. Wang, Y. Wang, X. Cai, C. Zhang, L. V. Wang, and Y. Xia. Labeling human mesenchymal stem cells with gold nanocages for in vitro and in vivo tracking by two-photon microscopy and photoacoustic microscopy. Theranostics 3:532–543, 2013.PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Zhao, X., J. Kim, C. A. Cezar, N. Huebsch, K. Lee, K. Bouhadir, and D. J. Mooney. Active scaffolds for on-demand drug and cell delivery. Proc. Natl. Acad. Sci. 108:67–72, 2011.PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Zhao, Q., J. Langley, S. Lee, and W. Liu. Positive contrast technique for the detection and quantification of superparamagnetic iron oxide nanoparticles in MRI. NMR Biomed. 24:464–472, 2011.PubMedCrossRefGoogle Scholar
  207. 207.
    Zhong, S., S. Shu, Z. Wang, J. Luo, W. Zhong, H. Ran, Y. Zheng, Y. Yin, and Z. Ling. Enhanced homing of mesenchymal stem cells to the ischemic myocardium by ultrasound-targeted microbubble destruction. Ultrasonics 52:281–286, 2012.PubMedCrossRefGoogle Scholar
  208. 208.
    Zhou, L., K. Dong, Z. Chen, J. Ren, and X. Qu. Near-infrared absorbing mesoporous carbon nanoparticle as an intelligent drug carrier for dual-triggered synergistic cancer therapy. Carbon 82:479–488, 2015.CrossRefGoogle Scholar
  209. 209.
    Zhou, B., D. Li, J. Qian, Z. Li, P. Pang, and H. Shan. MR tracking of SPIO-labeled mesenchymal stem cells in rats with liver fibrosis could not monitor the cells accurately. Contrast Media Mol. Imaging. 2015. doi: 10.1002/cmmi.1650.Google Scholar
  210. 210.
    Zhou, P., Y. Xia, X. Cheng, P. Wang, Y. Xie, and S. Xu. Enhanced bone tissue regeneration by antibacterial and osteoinductive silica-HACC-zein composite scaffolds loaded with rhBMP-2. Biomaterials 35:10033–10045, 2014.PubMedCrossRefGoogle Scholar
  211. 211.
    Zhu, Y., J. Shi, H. Chen, W. Shen, and X. Dong. A facile method to synthesize novel hollow mesoporous silica spheres and advanced storage property. Microporous Mesoporous Mater. 84:218–222, 2005.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringUniversity of Texas at AustinAustinUSA
  2. 2.School of Electrical and Computer Engineering, Georgia Institute of TechnologyAtlantaUSA
  3. 3.Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology, Emory University School of MedicineAtlantaUSA

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