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.