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The stiffness of living tissues and its implications for tissue engineering

Abstract

The past 20 years have witnessed ever-growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decade’s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.

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Fig. 1: Main mechanical deformations and representative curves.
Fig. 2: The stiffness of living tissues spans a full pascal-to-gigapascal range.
Fig. 3: Tissue mechanics are altered in disease states.
Fig. 4: Engineering of lifelike tissue mechanics.

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Acknowledgements

The authors gratefully acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia. The authors also thank the peer-reviewers for their constructive comments and suggestions that helped to shape the manuscript.

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C.F.G. and L.G. contributed to all aspects of the article. R.L.R. and A.P.M. contributed substantially to discussions of the article content and review or editing of the manuscript before submission. A.P.M. additionally contributed to writing the manuscript.

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Correspondence to Rui L. Reis.

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Guimarães, C.F., Gasperini, L., Marques, A.P. et al. The stiffness of living tissues and its implications for tissue engineering. Nat Rev Mater 5, 351–370 (2020). https://doi.org/10.1038/s41578-019-0169-1

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