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The Next Generation: Three-Dimensional Bioprinting of Acoustically Responsive Scaffolds The shape of an ARS is dictated by the shape of the con- tainer that holds the polymer solution as it is cross-linked into a solid material. Thus, there is a practical limit to what geometries can be achieved, and there is a limited ability to generate complex patterns of emulsions and hydrogel matrices. ARSs with patient-specific geometry (e.g., to fit in a wound area) as well as precise, spatial patterning of the hydrogel matrix and multiple phase- shift emulsions can further advance their applications in TERM. However, developing reproducible ARSs with the above-mentioned features requires advanced fabrica- tion methods beyond conventional bulk polymerization techniques. To do this, 3D bioprinting is used in the development of such ARSs through precise layer-by- layer deposition of the hydrogel component of the ARS or phase-shift emulsions within the ARS based on user- defined computer-aided design. Using an extrusion-based bioprinting technique, ARSs with spatially patterned phase-shift emulsions were fab- ricated (Figure 7) (Aliabouzar et al., 2022). ADV can be generated at significantly higher spatial resolutions in bioprinted ARSs compared with conventional ARSs. This implies that the ADV-induced modulation of biochemi- cal and biophysical cues could be spatially patterned at higher resolutions with 3D bioprinting. Additionally, bioprinting enabled micropatterning of both phase-shift emulsions and cells in distinct patterns in ARSs. Bioprinting offers another advantage of fabricating ARSs with different mechanical properties within each layer, which can provide a platform to tune the response of ADV-generated bubbles and, in turn, the associated biophysical and biochemical effects. Over- all, integrating ADV with 3D bioprinting, which is incredibly underdeveloped, can open new opportuni- ties in regenerative medicine. Final Thoughts Phase-shift emulsions, ARSs, and ADV are tools that can help unravel the complexities of tissue regeneration as well as drive the development of new, regenerative therapies via the modulation of biochemical and bio- physical cues. The ability to noninvasively modulate an ARS using ADV in an on-demand, spatiotemporally con- trolled manner is a dramatic paradigm shift compared with conventional hydrogels widely used within TERM. A better understanding of acoustically driven interactions in the ARS, particularly with cells, will help spur their translational advancement, both within TERM and in other applications. Acknowledgments This work was supported by National Institutes of Health Grants R21AR065010 and R01HL139656, the Focused Ultrasound Foundation, and the University of Michigan Basic Radiological Sciences Innovation Award. We thank Xiaoxiao Dong, Easton Farrell, Leidan Huang, Brock Humphries, Hai Jin, Xiaofang Lu, and Alexander Mon- cion for their contributions to this article. Figure 7. Three-dimensional (3D) bioprinting generated ARSs with complex structures. A: three phase-shift emulsions with different fluorescent payloads (i.e., red, yellow, and green dextran) were printed in a hydrogel matrix consisting of alginate and hyaluronic acid (left). Right: zoomed-in region of white box on left. B: reservoirs of emulsion (green) were printed in a matrix of fibrin and hyaluronic acid (red). Reprinted from Aliabouzar et al. (2022), with permission from Elsevier. Summer 2022 • Acoustics Today 21