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


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.


Photoacoustic microscopy Biomedical imaging Tissue engineering Regenerative medicine Non-invasive 



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.


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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

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