Abstract

Systems and devices for in vitro tissue modelling and engineering are valuable tools, which combine the strength between the controlled laboratory environment and the complex tissue organization and environment in vivo. Device-based tissue engineering is also a possible avenue for future explant culture in regenerative medicine. The most fundamental requirements on platforms intended for tissue modelling and engineering are their ability to shape and maintain cell aggregates over long-term culture. An emerging technology for tissue shaping and culture is ultrasonic standing wave (USW) particle manipulation, which offers label-free and gentle positioning and aggregation of cells. The pressure nodes defined by the USW, where cells are trapped in most cases, are stable over time and can be both static and dynamic depending on actuation schemes. In this review article, we highlight the potential of USW cell manipulation as a tool for tissue modelling and engineering.

Highlights

  • Acoustofluidics has, during the last 1–2 decades, emerged as a straightforward but yet powerful technique for the manipulation of particles and fluids inside micro- and mini-scaled fluid-filled channels and chambers [1]

  • While these results clearly show that adherent cells are able to form stable and functional cell–cell connections while trapped in an acoustic pressure node, and paving the way for ultrasonic standing wave (USW)-based tissue engineering, USW trapping could still alter cell functionality

  • A scaffold-free approach to tissue engineering based on acoustofluidics in its current form comes with two foreseeable limitations; within the pressure node, cells will be brought into immediate proximity due to force gradients and secondary forces; and the absence of a substrate may be a problem for some cell types

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Summary

Introduction

Acoustofluidics has, during the last 1–2 decades, emerged as a straightforward but yet powerful technique for the manipulation of particles and fluids inside micro- and mini-scaled fluid-filled channels and chambers [1]. The great majority of reported acoustofluidic applications utilized standing waves in the MHz-frequency regime, and actuation methods are typically based on either bulk acoustic waves (BAWs) [2] or surface acoustic waves (SAWs) [3]. Another term often used is acoustophoresis, which refers to the technology for manipulating suspended objects in a medium by the use of acoustic fields. In parallel with the general development of acoustofluidic technology, the concept of ultrasound-supported tissue engineering and modelling has gradually emerged. This review article will discuss these applications and the acoustofluidic technology developed and used for the specific purpose of engineering and modelling tissue

Cell Functionality in Ultrasonic Standing Wave Traps
Initital Cell Organization
Cell–Cell Connections in USW Trapping
Cell Behavior after USW Exposure
Cell Functionality and Behavior in Aggregates
Cell Patterning and Tissue Shaping
Single Pressure Node
Multiple Pressure Nodes
Pressure Node Patterns
Acoustic Streaming
Arbitrary Pressure Field by Acoustic Holography
Tissue Modelling and Engineering
Scaffold-Free Approach
Tumor Modelling by Spheroid Culture
Tissue-Engineered Cartilage Explants
Acoustic Hydrogel Hybrids
Possibilities for Clinical Use
Conclusions
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