The stiffness of living tissues and its implications for their engineering Carlos F. Guimarães, Luca Gasperini, Alexandra P. Marques, and Rui L. Reis review the mechanical properties of biological tissues and their importance in tissue engineering. Over the past 20 years, it has become clear that the mechanical properties of tissues, from nanoscale to macroscale, are crucial for cellular behavior and tissue function. This knowledge, combined with biochemical cues, has advanced biomaterial development, tissue engineering, and regenerative medicine. However, the literature on tissue mechanics varies widely in methodology and data. This review gathers key data on tissue stiffness and discusses the complexities of tissue stiffness from a materials perspective, highlighting challenges in engineering life-like tissues and proposing a unified view. Emerging advances in bioengineered tissue stiffness are also presented, along with differences and similarities between healthy and diseased tissues, and various techniques for characterizing tissue stiffness at different scales. The concept of stiffness relates to the mechanical properties of materials, particularly their resistance to deformation. Stiffness is determined by the ratio of load to deformation. Materials used in manufacturing are generally stiffer than human tissues. The stiffness of biological tissues varies widely, with some foodstuffs having stiffness comparable to tissues. Stiffness is a structural property influenced by material composition, amount, and distribution. For example, bones have a high stiffness-to-weight ratio due to their hollow structure. Moduli and stiffness are related concepts, with moduli describing material properties and stiffness reflecting the final structure's properties. Stiffness is a critical factor in tissue engineering, as it affects cellular behavior and tissue function. The mechanical properties of cells and tissues are influenced by their environment, with cells having characteristic stiffness due to interactions with their surroundings. For example, cancer cells often have altered stiffness. The review discusses the mechanical properties of tissues at different scales, from ECM molecules and single cells to bulk tissues and organs. It emphasizes the importance of considering both static and dynamic mechanics in tissue engineering. The review also discusses the time and spatial scales of tissue mechanics. Time-dependent behavior, such as viscoelasticity, is important in understanding tissue response to different deformation speeds. Spatial scales, including nanoscale and microscale features, are also critical, as they influence cell behavior and tissue mechanics. The mechanical properties of tissues are influenced by their structure, with ECM components like collagen and elastin playing key roles. The stiffness of tissues is affected by the ratio of elastin to collagen, with higher ratios leading to more compliant structures. The review highlights the importance of understanding the mechanical properties of cells and tissues, including their interactions with the ECM and each other. The mechanical properties of cells are influenced by their environment, with cells having varying stiffness depending on their type and state. The review also discusses the mechanical properties of tissues at different scales, emphasizing the need for standardized methods to characterize tissue stiffness. The mechanical properties of tissues are influenced by their structure,The stiffness of living tissues and its implications for their engineering Carlos F. Guimarães, Luca Gasperini, Alexandra P. Marques, and Rui L. Reis review the mechanical properties of biological tissues and their importance in tissue engineering. Over the past 20 years, it has become clear that the mechanical properties of tissues, from nanoscale to macroscale, are crucial for cellular behavior and tissue function. This knowledge, combined with biochemical cues, has advanced biomaterial development, tissue engineering, and regenerative medicine. However, the literature on tissue mechanics varies widely in methodology and data. This review gathers key data on tissue stiffness and discusses the complexities of tissue stiffness from a materials perspective, highlighting challenges in engineering life-like tissues and proposing a unified view. Emerging advances in bioengineered tissue stiffness are also presented, along with differences and similarities between healthy and diseased tissues, and various techniques for characterizing tissue stiffness at different scales. The concept of stiffness relates to the mechanical properties of materials, particularly their resistance to deformation. Stiffness is determined by the ratio of load to deformation. Materials used in manufacturing are generally stiffer than human tissues. The stiffness of biological tissues varies widely, with some foodstuffs having stiffness comparable to tissues. Stiffness is a structural property influenced by material composition, amount, and distribution. For example, bones have a high stiffness-to-weight ratio due to their hollow structure. Moduli and stiffness are related concepts, with moduli describing material properties and stiffness reflecting the final structure's properties. Stiffness is a critical factor in tissue engineering, as it affects cellular behavior and tissue function. The mechanical properties of cells and tissues are influenced by their environment, with cells having characteristic stiffness due to interactions with their surroundings. For example, cancer cells often have altered stiffness. The review discusses the mechanical properties of tissues at different scales, from ECM molecules and single cells to bulk tissues and organs. It emphasizes the importance of considering both static and dynamic mechanics in tissue engineering. The review also discusses the time and spatial scales of tissue mechanics. Time-dependent behavior, such as viscoelasticity, is important in understanding tissue response to different deformation speeds. Spatial scales, including nanoscale and microscale features, are also critical, as they influence cell behavior and tissue mechanics. The mechanical properties of tissues are influenced by their structure, with ECM components like collagen and elastin playing key roles. The stiffness of tissues is affected by the ratio of elastin to collagen, with higher ratios leading to more compliant structures. The review highlights the importance of understanding the mechanical properties of cells and tissues, including their interactions with the ECM and each other. The mechanical properties of cells are influenced by their environment, with cells having varying stiffness depending on their type and state. The review also discusses the mechanical properties of tissues at different scales, emphasizing the need for standardized methods to characterize tissue stiffness. The mechanical properties of tissues are influenced by their structure,