Skip to main content

Advertisement

Log in

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

  • Nondestructive Characterization of Biomaterials for Tissue Engineering and Drug Delivery
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Beard, P. Biomedical photoacoustic imaging. Interface Focus 1:602–631, 2011. doi:10.1098/rsfs.2011.0028.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  11. Cai, X., Y. S. Zhang, Y. Xia, and L. V. Wang. Photoacoustic microscopy in tissue engineering. Mater. Today 16:67–77, 2013.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen, F., P. W. Tillberg, and E. S. Boyden. Expansion microscopy. Science 347:1260088, 2015.

    Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  18. Discovery Through Color—A Guide to Multiple Antigen Labeling. Burlingame: Vector Laboratories, 2005.

  19. Durnin, J., J. H. Eberly, and J. J. Miceli. Comparison of Bessel and Gaussian beams. Opt. Lett. 13:79–80, 1988.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Korner, A., and J. Pawelek. Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science 217:1163–1165, 1982.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Langer, R., and J. P. Vacanti. Tissue engineering. Science 260:920–926, 1993.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  42. Liu, Y., C. Zhang, and L. V. Wang. Effects of light scattering on optical-resolution photoacoustic microscopy. J. Biomed. Opt. 17:126014, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ma, P. X. Scaffolds for tissue fabrication. Mater. Today 7:30–40, 2004.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ntziachristos, V. Going deeper than microscopy: the optical imaging frontier in biology. Nat. Methods 7:603–614, 2010.

    Article  CAS  PubMed  Google Scholar 

  47. Ntziachristos, V., and D. Razansky. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem. Rev. 110:2783–2794, 2010.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  52. Seidler, E. The tetrazolium–formazan system: design and histochemistry. Prog. Histochem. Cytochem. 24:1–86, 1991.

    Article  CAS  PubMed  Google Scholar 

  53. Shaner, N. C., P. A. Steinbach, and R. Y. Tsien. A guide to choosing fluorescent proteins. Nat. Methods 2:905–909, 2005.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Song, K. H., and L. V. Wang. Deep reflection-mode photoacoustic imaging of biological tissue. J. Biomed. Opt. 12:060503, 2007.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  58. Taruttis, A., and V. Ntziachristos. Advances in real-time multispectral optoacoustic imaging and its applications. Nat. Photon. 9:219–227, 2015.

    Article  CAS  Google Scholar 

  59. Wang, L. V. Multiscale photoacoustic microscopy and computed tomography. Nat. Photon. 3:503–509, 2009.

    Article  CAS  Google Scholar 

  60. Wang, L. V., and S. Hu. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335:1458–1462, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Yao, J., and L. V. Wang. Photoacoustic microscopy. Laser Photon. Rev. 7:758–778, 2013.

    Article  Google Scholar 

  71. Yuste, R. Fluorescence microscopy today. Nat. Methods 2:902–904, 2005.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  75. Zhang, Y. S., S.-W. Choi, and Y. Xia. Inverse opal scaffolds for applications in regenerative medicine. Soft Matter 9:9747–9754, 2013.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Zhang, Y. S., and Y. Xia. Multiple facets for extracellular matrix mimicking in regenerative medicine. Nanomedicine 10:689–692, 2015.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lihong V. Wang or Younan Xia.

Additional information

Associate Editor Rebecca Kuntz-Willits oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y.S., Wang, L.V. & Xia, Y. Seeing Through the Surface: Non-invasive Characterization of Biomaterial–Tissue Interactions Using Photoacoustic Microscopy. Ann Biomed Eng 44, 649–666 (2016). https://doi.org/10.1007/s10439-015-1485-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-015-1485-2

Keywords

Navigation