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  • Review Article
  • Published:

Ultrasound-assisted tissue engineering

Abstract

Combining cells, biomaterials and bioactive factors with biophysical cues to engineer cell and tissue constructs can address various applications, such as regenerative and personalized medicine, in addition to drug discovery and testing. However, challenges associated with the assembly of large, complex tissues integrating multiple cell types and functions require established technologies such as 3D printing to be combined with cell-assembly and cell-stimulation methods. Ultrasound is a potential tool for advancing tissue engineering, conferring the advantages of cytocompatibility and deep tissue penetration. In this Review, we discuss the application of ultrasound to the remote manipulation and assembly of biological building blocks, as well as the direct and indirect triggering of cellular processes, in combination with ultrasound-sensitive additives. Furthermore, we examine the role of ultrasound in tissue maturation, and in affecting the microenvironment and cell programming. Finally, we outline the challenges facing the technology and considerations for the widespread use of ultrasound in tissue engineering.

Key points

  • Ultrasound is a versatile and biocompatible method to remotely apply forces and transfer energy, with diverse potential applications in tissue engineering.

  • Parallel and rapid assembly of cells can be achieved by using ultrasound techniques in standalone setups or in combination with bioprinting to yield multilayer constructs with high local cell density.

  • Ultrasound can spatiotemporally alter the biochemical and biomechanical properties of scaffold materials to influence the fate of engineered cells and tissues.

  • Ultrasound can couple to cellular and molecular processes, manipulating cell behaviour and tissue morphogenesis.

  • Ultrasound methodologies will benefit from standardized protocols and instruments to allow widespread adoption in the tissue-engineering community.

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Fig. 1: Using sound waves within fabrication and maturation of biological tissues.
Fig. 2: Shaping of ultrasound fields and their use for directed assembly.
Fig. 3: Ultrasound for cell maturation and reprogramming.

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Acknowledgements

The research was in part supported by the European Research Council under the ERC Advanced Grant Agreement HOLOMAN (no. 788296); and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) under Germany’s Excellence Strategy through the Excellence Cluster 3D Matter Made to Order (EXC-2082/1-390761711) and the Carl-Zeiss-Stiftung (P2022-04-073).

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Correspondence to Kai Melde or Peer Fischer.

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K.M. and P.F. are inventors on a patent related to this work granted by the European Patent Office (EP3034281 B1). K.M. and P.F. declare no other competing interests. The remaining authors declare no competing interests.

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Melde, K., Athanassiadis, A.G., Missirlis, D. et al. Ultrasound-assisted tissue engineering. Nat Rev Bioeng 2, 486–500 (2024). https://doi.org/10.1038/s44222-024-00166-5

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