Advertisement

Annals of Biomedical Engineering

, Volume 44, Issue 3, pp 649–666 | Cite as

Seeing Through the Surface: Non-invasive Characterization of Biomaterial–Tissue Interactions Using Photoacoustic Microscopy

  • Yu Shrike Zhang
  • Lihong V. Wang
  • Younan Xia
Nondestructive Characterization of Biomaterials for Tissue Engineering and Drug Delivery

Abstract

At the intersection of life sciences, materials science, engineering, and medicine, regenerative medicine stands out as a rapidly progressing field that aims at retaining, restoring, or augmenting tissue/organ functions to promote the human welfare. While the field has witnessed tremendous advancements over the past few decades, it still faces many challenges. For example, it has been difficult to visualize, monitor, and assess the functions of the engineered tissue/organ constructs, particularly when three-dimensional scaffolds are involved. Conventional approaches based on histology are invasive and therefore only convey end-point assays. The development of volumetric imaging techniques such as confocal and ultrasonic imaging has enabled direct observation of intact constructs without the need of sectioning. However, the capability of these techniques is often limited in terms of penetration depth and contrast. In comparison, the recently developed photoacoustic microscopy (PAM) has allowed us to address these issues by integrating optical and ultrasonic imaging to greatly reduce the effect of tissue scattering of photons with one-way ultrasound detection while retaining the high optical absorption contrast. PAM has been successfully applied to a number of studies, such as observation of cell distribution, monitoring of vascularization, and interrogation of biomaterial degradation. In this review article, we highlight recent progress in non-invasive and volumetric characterization of biomaterial–tissue interactions using PAM. We also discuss challenges ahead and envision future directions.

Keywords

Photoacoustic microscopy Biomedical imaging Tissue engineering Regenerative medicine Non-invasive 

Notes

Acknowledgment

This work was supported in part by startup funds from the Georgia Institute of Technology and NIH Grants DP1 OD000798 (NIH Director’s Pioneer Award) and R01 AR060820. The authors would like to thank Dr. Yu Wang and Dr. Li Li for their assistance in OR-PAM–FCM and OR-PAM–OCT imaging of melanoma cell-scaffold interactions.

Conflict of interest

L. V. Wang has a financial interest in Endra, Inc., and Microphotoacoustics, Inc., which, however, did not support this work; all other authors declare no conflict of interest.

References

  1. 1.
    Allen, T. J., A. Hall, A. P. Dhillon, J. S. Owen, and P. C. Beard. Spectroscopic photoacoustic imaging of lipid-rich plaques in the human aorta in the 740 to 1400 nm wavelength range. J. Biomed. Opt. 17:0612091–06120910, 2012.CrossRefGoogle Scholar
  2. 2.
    Appel, A., M. A. Anastasio, and E. M. Brey. Potential for imaging engineered tissues with x-ray phase contrast. Tissue Eng. B. 17:321–330, 2011.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Artzi, N., N. Oliva, C. Puron, S. Shitreet, S. Artzi, A. Bon Ramos, A. Groothuis, G. Sahagian, and E. R. Edelman. In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging. Nat. Mater. 10:704–709, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bae, H., A. S. Puranik, R. Gauvin, F. Edalat, B. Carrillo-Conde, N. A. Peppas, and A. Khademhosseini. Building vascular networks. Sci. Transl. Med. 4:160ps23, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Beard, P. Biomedical photoacoustic imaging. Interface Focus 1:602–631, 2011. doi: 10.1098/rsfs.2011.0028.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brunker, J., and P. Beard. Pulsed photoacoustic doppler flowmetry using time-domain cross-correlation: accuracy, resolution and scalability. J. Acoust. Soc. Am. 132:1780–1791, 2012.CrossRefPubMedGoogle Scholar
  8. 8.
    Cai, X., L. Li, A. Krumholz, Z. Guo, T. N. Erpelding, C. Zhang, Y. Zhang, Y. Xia, and L. V. Wang. Multi-scale molecular photoacoustic tomography of gene expression. PLoS One 7:e43999, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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. C 18:310–317, 2012.CrossRefGoogle Scholar
  10. 10.
    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 3d porous scaffolds in vivo by photoacoustic microscopy and optical coherence tomography. Tissue Eng. C 19:196–204, 2013.CrossRefGoogle Scholar
  11. 11.
    Cai, X., Y. S. Zhang, Y. Xia, and L. V. Wang. Photoacoustic microscopy in tissue engineering. Mater. Today 16:67–77, 2013.CrossRefGoogle Scholar
  12. 12.
    Chatni, M. R., J. Xia, R. Sohn, K. Maslov, Z. Guo, Y. Zhang, K. Wang, Y. Xia, M. Anastasio, J. Arbeit, and L. V. Wang. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography. J. Biomed. Opt. 17:076012–076017, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chen, F., P. W. Tillberg, and E. S. Boyden. Expansion microscopy. Science 347:1260088, 2015.Google Scholar
  14. 14.
    Cho, E. C., C. Kim, F. Zhou, C. M. Cobley, K. H. Song, J. Chen, Z.-Y. Li, L. V. Wang, and Y. Xia. Measuring the optical absorption cross sections of Au–Ag nanocages and au nanorods by photoacoustic imaging. J. Phys. Chem. C 113:9023–9028, 2009.CrossRefGoogle Scholar
  15. 15.
    Chung, K., J. Wallace, S.-Y. Kim, S. Kalyanasundaram, A. S. Andalman, T. J. Davidson, J. J. Mirzabekov, K. A. Zalocusky, J. Mattis, and A. K. Denisin. Structural and molecular interrogation of intact biological systems. Nature 497:332–337, 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Daniel, R., D. Martin, V. Claudio, M. Rui, P. Norbert, W. K. Reinhard, and N. Vasilis. Multispectral opto-acoustic tomography of deep-seated fluorescent proteins in vivo. Nat. Photon. 3:412–417, 2009.CrossRefGoogle Scholar
  17. 17.
    Del Guerra, A., and N. Belcari. State-of-the-art of PET, SPECT and CT for small animal imaging. Nucl. Instrum. Methods. Phys. Res. A 583:119–124, 2007.CrossRefGoogle Scholar
  18. 18.
    Discovery Through Color—A Guide to Multiple Antigen Labeling. Burlingame: Vector Laboratories, 2005.Google Scholar
  19. 19.
    Durnin, J., J. H. Eberly, and J. J. Miceli. Comparison of Bessel and Gaussian beams. Opt. Lett. 13:79–80, 1988.CrossRefPubMedGoogle Scholar
  20. 20.
    Favazza, C. P., O. Jassim, L. A. Cornelius, and L. V. Wang. In vivo photoacoustic microscopy of human cutaneous microvasculature and a nevus. J. Biomed. Opt. 16:016015, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fernández-López, C., L. Polavarapu, D. M. Solís, J. M. Taboada, F. Obelleiro, R. Contreras-Cáceres, I. Pastoriza-Santos, and J. Pérez-Juste. Gold nanorod–pNIPAM hybrids with reversible plasmon coupling: synthesis, modeling, and SERS properties. ACS Appl. Mater. Interfaces 7:12530–12538, 2015.CrossRefPubMedGoogle Scholar
  22. 22.
    Filonov, G. S., A. Krumholz, J. Xia, J. Yao, L. V. Wang, and V. V. Verkhusha. Deep-tissue photoacoustic tomography of a genetically encoded near-infrared fluorescent probe. Angew. Chem. Int. Ed. 51:1448–1451, 2012.CrossRefGoogle Scholar
  23. 23.
    Freed, L. E., G. Vunjak-Novakovic, R. J. Biron, D. B. Eagles, D. C. Lesnoy, S. K. Barlow, and R. Langer. Biodegradable polymer scaffolds for tissue engineering. Nat. Biotechnol. 12:689–693, 1994.CrossRefGoogle Scholar
  24. 24.
    Gottschalk, S., T. F. Fehm, X. L. Deán-Ben, and D. Razansky. Noninvasive real-time visualization of multiple cerebral hemodynamic parameters in whole mouse brains using five-dimensional optoacoustic tomography. J. Cereb. Blood Flow Metab. 35:531–535, 2015.CrossRefPubMedGoogle Scholar
  25. 25.
    Horwitz, J. P., J. Chua, R. J. Curby, A. J. Tomson, M. A. Da Rooge, B. E. Fisher, J. Mauricio, and I. Klundt. Substrates for cytochemical demonstration of enzyme activity. I. Some substituted 3-indolyl-β-d-glycopyranosides. J. Med. Chem. 7:574–575, 1964.CrossRefPubMedGoogle Scholar
  26. 26.
    Hu, S., K. Maslov, and L. V. Wang. Second-generation optical-resolution photoacoustic microscopy with improved sensitivity and speed. Opt. Lett. 36:1134–1136, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jansen, K., A. F. W. Van Der Steen, M. Wu, H. M. M. Van Beusekom, G. Springeling, X. Li, Q. Zhou, K. Kirk Shung, D. P. V. De Kleijn, and G. Van Soest. Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis. J. Biomed. Opt. 19:026006, 2014.CrossRefPubMedGoogle Scholar
  28. 28.
    Jathoul, A. P., J. Laufer, O. Ogunlade, B. Treeby, B. Cox, E. Zhang, P. Johnson, A. R. Pizzey, B. Philip, T. Marafioti, M. F. Lythgoe, R. B. Pedley, M. A. Pule, and P. Beard. Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter. Nat. Photon. 9:239–246, 2015.Google Scholar
  29. 29.
    Kim, C., C. Favazza, and L. V. Wang. In vivo photoacoustic tomography of chemicals: high-resolution functional and molecular optical imaging at new depths. Chem. Rev. 110:2756–2782, 2010.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kim, K., C. G. Jeong, and S. J. Hollister. Non-invasive monitoring of tissue scaffold degradation using ultrasound elasticity imaging. Acta Biomater. 4:783–790, 2008.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Korner, A., and J. Pawelek. Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science 217:1163–1165, 1982.CrossRefPubMedGoogle Scholar
  32. 32.
    Kruger, R. A., R. B. Lam, D. R. Reinecke, S. P. Del Rio, and R. P. Doyle. Photoacoustic angiography of the breast. Med. Phys. 37:6096–6100, 2010.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Krumholz, A., D. M. Shcherbakova, J. Xia, L. V. Wang, and V. V. Verkhusha. Multicontrast photoacoustic in vivo imaging using near-infrared fluorescent proteins. Sci. Rep. 4:3939, 2014. doi: 10.1038/srep03939.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Krumholz, A., S. J. Vanvickle-Chavez, J. Yao, T. P. Fleming, W. E. Gillanders, and L. V. Wang. Photoacoustic microscopy of tyrosinase reporter gene in vivo. J. Biomed. Opt. 16:080503, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Langer, R., and J. P. Vacanti. Tissue engineering. Science 260:920–926, 1993.CrossRefPubMedGoogle Scholar
  36. 36.
    Laufer, J., A. Jathoul, M. Pule, and P. Beard. In vitro characterization of genetically expressed absorbing proteins using photoacoustic spectroscopy. Biomed. Opt. Express 4:2477–2490, 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Li, L., K. Maslov, G. Ku, and L. V. Wang. Three-dimensional combined photoacoustic and optical coherence microscopy for in vivo microcirculation studies. Opt. Express 17:16450–16455, 2009.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Li, L., R. J. Zemp, G. Lungu, G. Stoica, and L. V. Wang. Photoacoustic imaging of lacZ gene expression in vivo. J. Biomed. Opt. 12:020504, 2007.CrossRefPubMedGoogle Scholar
  39. 39.
    Li, M.-L., H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang. Improved in vivo photoacoustic microscopy based on a virtual-detector concept. Opt. Lett. 31:474–476, 2006.CrossRefPubMedGoogle Scholar
  40. 40.
    Li, L., H. F. Zhang, R. J. Zemp, K. Maslov, and L. V. Wang. Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy. J. Innov. Opt. Health Sci. 1:207–215, 2008.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Liao, C. K., M. L. Li, and P. C. Li. Optoacoustic imaging with synthetic aperture focusing and coherence weighting. Opt. Lett. 29:2506–2508, 2004.CrossRefPubMedGoogle Scholar
  42. 42.
    Liu, Y., C. Zhang, and L. V. Wang. Effects of light scattering on optical-resolution photoacoustic microscopy. J. Biomed. Opt. 17:126014, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Ma, P. X. Scaffolds for tissue fabrication. Mater. Today 7:30–40, 2004.CrossRefGoogle Scholar
  44. 44.
    Mansour, S. L., K. R. Thomas, C. X. Deng, and M. R. Capecchi. Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination. Proct. Natl. Acad. Sci. USA 87:7688–7692, 1990.CrossRefGoogle Scholar
  45. 45.
    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:e37267, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Ntziachristos, V. Going deeper than microscopy: the optical imaging frontier in biology. Nat. Methods 7:603–614, 2010.CrossRefPubMedGoogle Scholar
  47. 47.
    Ntziachristos, V., and D. Razansky. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem. Rev. 110:2783–2794, 2010.CrossRefPubMedGoogle Scholar
  48. 48.
    O’Donnell, M., C.-W. Wei, J. Xia, I. Pelivanov, C. Jia, S.-W. Huang, X. Hu, and X. Gao. Can molecular imaging enable personalized diagnostics? An example using magnetomotive photoacoustic imaging. Ann. Biomed. Eng. 41:2237–2247, 2013.CrossRefPubMedGoogle Scholar
  49. 49.
    Peptan, I. A., L. Hong, H. Xu, and R. L. Magin. Mr assessment of osteogenic differentiation in tissue-engineered constructs. Tissue Eng. 12:843–851, 2006.CrossRefPubMedGoogle Scholar
  50. 50.
    Phelps, E. A., N. Landázuri, P. M. Thulé, W. R. Taylor, and A. J. García. Bioartificial matrices for therapeutic vascularization. Proc. Natl. Acad. Sci. USA 107:3323–3328, 2009.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Rajian, J. R., R. Li, P. Wang, and J.-X. Cheng. Vibrational photoacoustic tomography: chemical imaging beyond the ballistic regime. J. Phys. Chem. Lett. 4:3211–3215, 2013.CrossRefGoogle Scholar
  52. 52.
    Seidler, E. The tetrazolium–formazan system: design and histochemistry. Prog. Histochem. Cytochem. 24:1–86, 1991.CrossRefPubMedGoogle Scholar
  53. 53.
    Shaner, N. C., P. A. Steinbach, and R. Y. Tsien. A guide to choosing fluorescent proteins. Nat. Methods 2:905–909, 2005.CrossRefPubMedGoogle Scholar
  54. 54.
    Song, Y., D. Treanor, A. J. Bulpitt, and D. R. Magee. 3d reconstruction of multiple stained histology images. J. Pathol. Inform. 4:S7, 2013. doi: 10.4103/2153-3539.109864.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Song, K. H., and L. V. Wang. Deep reflection-mode photoacoustic imaging of biological tissue. J. Biomed. Opt. 12:060503, 2007.CrossRefPubMedGoogle Scholar
  56. 56.
    Spencer, J. A., F. Ferraro, E. Roussakis, A. Klein, J. Wu, J. M. Runnels, W. Zaher, L. J. Mortensen, C. Alt, and R. Turcotte. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 508:269–273, 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    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. C 20:440–449, 2014.CrossRefGoogle Scholar
  58. 58.
    Taruttis, A., and V. Ntziachristos. Advances in real-time multispectral optoacoustic imaging and its applications. Nat. Photon. 9:219–227, 2015.CrossRefGoogle Scholar
  59. 59.
    Wang, L. V. Multiscale photoacoustic microscopy and computed tomography. Nat. Photon. 3:503–509, 2009.CrossRefGoogle Scholar
  60. 60.
    Wang, L. V., and S. Hu. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335:1458–1462, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Wang, Y., S. Hu, K. Maslov, Y. Zhang, Y. Xia, and L. V. Wang. In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure. Opt. Lett. 36:1029–1031, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wang, L., S. L. Jacques, and L. Zheng. MCML—Monte Carlo modeling of light transport in multi-layered tissues. Comput. Methods Programs Biomed. 47:131–146, 1995.CrossRefPubMedGoogle Scholar
  63. 63.
    Wang, B., A. Karpiouk, D. Yeager, J. Amirian, S. Litovsky, R. Smalling, and S. Emelianov. Intravascular photoacoustic imaging of lipid in atherosclerotic plaques in the presence of luminal blood. Opt. Lett. 37:1244–1246, 2012.CrossRefPubMedGoogle Scholar
  64. 64.
    Wang, P., T. Ma, M. N. Slipchenko, S. Liang, J. Hui, K. K. Shung, S. Roy, M. Sturek, Q. Zhou, Z. Chen, and J.-X. Cheng. High-speed intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque enabled by a 2-kHz barium nitrite Raman laser. Sci. Rep. 4:6889, 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Wang, L., K. Maslov, and L. V. Wang. Single-cell label-free photoacoustic flowoxigraphy in vivo. Proc. Natl. Acad. Sci. USA 110:5759–5764, 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Wang, Y., K. Maslov, Y. Zhang, S. Hu, L. Yang, Y. Xia, J. Liu, and L. V. Wang. Fiber-laser-based photoacoustic microscopy and melanoma cell detection. J. Biomed. Opt. 16:011014, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Wang, X., Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang. Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain. Nat. Biotechnol. 21:803–806, 2003.CrossRefPubMedGoogle Scholar
  68. 68.
    Xia, Y., W. Li, C. M. Cobley, J. Chen, X. Xia, Q. Zhang, M. Yang, E. C. Cho, and P. K. Brown. Gold nanocages: from synthesis to theranostic applications. Acc. Chem. Res. 44:914–924, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Yao, J., K. I. Maslov, Y. Zhang, Y. Xia, and L. V. Wang. Label-free oxygen-metabolic photoacoustic microscopy in vivo. J. Biomed. Opt. 16:076003–076011, 2011.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Yao, J., and L. V. Wang. Photoacoustic microscopy. Laser Photon. Rev. 7:758–778, 2013.CrossRefGoogle Scholar
  71. 71.
    Yuste, R. Fluorescence microscopy today. Nat. Methods 2:902–904, 2005.CrossRefPubMedGoogle Scholar
  72. 72.
    Zhang, Y., X. Cai, S.-W. Choi, C. Kim, L. V. Wang, and Y. Xia. Chronic label-free volumetric photoacoustic microscopy of melanoma cells in three-dimensional porous scaffolds. Biomaterials 31:8651–8658, 2010.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Zhang, Y., X. Cai, Y. Wang, C. Zhang, L. Li, S.-W. Choi, L. V. Wang, and Y. Xia. Noninvasive photoacoustic microscopy of living cells in two and three dimensions through enhancement by a metabolite dye. Angew. Chem. Int. Ed. 50:7359–7363, 2011.CrossRefGoogle Scholar
  74. 74.
    Zhang, Y., X. Cai, J. Yao, L. V. Wang, and Y. Xia. Non-invasive and in situ characterization of the degradation of biomaterial scaffolds by photoacoustic microscopy. Angew. Chem. Int. Ed. 53:184–188, 2014.CrossRefGoogle Scholar
  75. 75.
    Zhang, Y. S., S.-W. Choi, and Y. Xia. Inverse opal scaffolds for applications in regenerative medicine. Soft Matter 9:9747–9754, 2013.CrossRefGoogle Scholar
  76. 76.
    Zhang, H. F., K. Maslov, M. Sivaramakrishnan, G. Stoica, and L. V. Wang. Imaging of hemoglobin oxygen saturation variations in single vessels in vivo using photoacoustic microscopy. Appl. Phys. Lett. 90:053901–053903, 2007.CrossRefGoogle Scholar
  77. 77.
    Zhang, H. F., K. Maslov, G. Stoica, and L. V. Wang. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nat. Biotechnol. 24:848–851, 2006.CrossRefPubMedGoogle Scholar
  78. 78.
    Zhang, C., K. Maslov, and L. V. Wang. Subwavelength-resolution label-free photoacoustic microscopy of optical absorption in vivo. Opt. Lett. 35:3195–3197, 2010.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Zhang, Y., Y. Wang, L. Wang, Y. Wang, X. Cai, C. Zhang, L. V. Wang, and Y. Xia. Labeling human mesenchymal stem cells with au nanocages for in vitro and in vivo tracking by two-photon microscopy and photoacoustic microscopy. Theranostics 3:532–543, 2013.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Zhang, Y. S., and Y. Xia. Multiple facets for extracellular matrix mimicking in regenerative medicine. Nanomedicine 10:689–692, 2015.CrossRefPubMedGoogle Scholar
  81. 81.
    Zhang, Y. S., J. J. Yao, C. Zhang, L. Li, L. H. V. Wang, and Y. N. Xia. Optical-resolution photoacoustic microscopy for volumetric and spectral analysis of histological and immunochemical samples. Angew. Chem. Int. Ed. 53:8099–8103, 2014.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  1. 1.Department of Medicine, Biomaterials Innovation Research Center, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Harvard-MIT Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Wyss Institute for Biologically Inspired EngineeringHarvard UniversityBostonUSA
  4. 4.Department of Biomedical EngineeringWashington University in St. LouisSt. LouisUSA
  5. 5.The Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology and Emory UniversityAtlantaUSA
  6. 6.School of Chemistry and Biochemistry, School of Chemical and Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaUSA

Personalised recommendations