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

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.