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FEATURED ARTICLE Building Blood Vessels and Beyond Using Bubbles Mitra Aliabouzar and Mario L. Fabiilli Introduction The axolotl (Ambystoma mexicanum), a type of salaman- der (see tinyurl.com/59u26vdm), has an incredible ability to regenerate entire limbs and other body parts that become damaged. Although humans are unable to match the axolotl, the capability of the human body to repair wounds is ultimately critical for our survival. Wound healing is a complex process driven by cells initially present at the wound site as well as cells that migrate into the wound environment. In general, cell behavior is guided by biochemical and biophysical “cues” in the local environment. Biochemical cues (e.g., proteins) are molecular in nature, whereas biophysical cues (e.g., stiff- ness) are mechanical and/or structural characteristics of the environment surrounding a cell. In the human body, the extracellular matrix is the environment surrounding each cell within solid tissue and contains large molecules like proteins and carbohydrates. These biochemical and biophysical cues, which are regulated in both space and time by intricate path- ways, cause a cell to undergo processes that directly or indirectly facilitate wound healing. Many wounds like minor cuts, scrapes, and bruises heal without a visit to a doctor’s office. Other wounds may necessitate medical treatments like stitches or an orthopedic cast in addi- tion to pharmaceuticals for the wound to properly heal. Surgical reconstruction and/or organ transplantation is needed when tissues or organs are severely damaged by trauma (e.g., car accident) or disease (e.g., cardio- vascular, cancer). These higher risk and more invasive interventions are required when the damaged tissues or organs have a very limited ability to regain their struc- ture and function via the body’s normal wound-healing mechanisms. Unfortunately, there is a practical limit to the types of defects that can be surgically reconstructed. Moreover, some patients do not qualify for surgery because of other medical issues. Complicating matters further, the demand for organ transplantation exceeds the supply of donated organs and organ recipients often require long-term immunosuppressive drugs, both of which impact morbidity and quality of life. Tissue Engineering and Regenerative Medicine The field of tissue engineering and regenerative medi- cine (TERM) seeks to overcome limitations associated with conventional, medical interventions like surgery and organ transplantation. The goal of TERM is the development of biological constructs that facilitate res- toration, maintenance, or regeneration of impaired or injured tissues/organs. A common strategy within TERM is the preprogrammed design of a construct consist- ing of a biocompatible scaffold loaded with cells and/ or biochemical cues (Figure 1A). The scaffold provides a three-dimensional (3D) microenvironment for cells, thereby mimicking the function of the extracellular matrix. The scaffold component of the construct often consists of a hydrogel, which is a porous, water-laden matrix con- sisting of natural (e.g., fibrin, collagen) or synthetic (e.g., dextran, polyethylene glycol) polymers. Hydrogels are made by cross-linking solutions of polymers to yield a solid-like material. Many commonly used hydrogels in TERM are biodegradable, which can assist with regenera- tive processes because they stay as long as needed and then disappear over time. Constructs are implanted inside a living organism to assist with tissue regeneration. However, a problem with preprogramming the design of a construct is that it involves manipulating the physiochemical properties of the scaffold and its precursor components before the con- struct is implanted. This manipulation yields constructs with predefined patterns of biochemical and biophysical cues. For example, with hydrogels, the composition of the ©2022 Acoustical Society of America. All rights reserved. 14 Acoustics Today • Summer 2022 | Volume 18, issue 2 https://doi.org/10.1121/AT.2022.18.2.14