The emergence of solid stress as a potent biomechanical marker of tumour progression.

Cancer is a disease of dysregulated mechanics which alters cell behaviour, compromises tissue structure, and promotes tumour growth and metastasis. In the context of tumour progression, the most widely studied of biomechanical markers is matrix stiffness as tumour tissue is typically stiffer than healthy tissue. However, solid stress has recently been identified as another marker of tumour growth, with findings strongly suggesting that its role in cancer is distinct from that of stiffness. Owing to the relative infancy of the field which draws from diverse disciplines, a comprehensive knowledge of the relationships between solid stress, tumorigenesis, and metastasis is likely to provide new and valuable insights. In this review, we discuss the micro- and macro-scale biomechanical interactions that give rise to solid stresses, and also examine the techniques developed to quantify solid stress within the tumour environment. Moreover, by reviewing the effects of solid stress on tissues, cancer and stromal cells, and signalling pathways, we also detail its mode of action at each level of the cancer cascade.

Bio-inspired design of a magnetically active trilayered scaffold for cartilage tissue engineering.

An important topic in cartilage tissue engineering is the development of biomimetic scaffolds which mimic the depth-dependent material properties of the native tissue. We describe an advanced trilayered nanocomposite hydrogel (ferrogel) with a gradient in compressive modulus from the top to the bottom layers (p < 0.05) of the construct. Further, the scaffold was able to respond to remote external stimulation, exhibiting an elastic, depth-dependent strain gradient. When bovine chondrocytes were seeded into the ferrogels and cultured for up to 14 days, there was good cell viability and a biochemical gradient was measured with sulphated glycosaminoglycan increasing with depth from the surface. This novel construct provides tremendous scope for tailoring location-specific cartilage replacement tissue; by varying the density of magnetic nanoparticles, concentration of base hydrogel and number of cells, physiologically relevant depth-dependent gradients may be attained. © 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Patient-specific fracture risk assessment of vertebrae: A multiscale approach coupling X-ray physics and continuum micromechanics.

While in clinical settings, bone mineral density measured by computed tomography (CT) remains the key indicator for bone fracture risk, there is an ongoing quest for more engineering mechanics-based approaches for safety analyses of the skeleton. This calls for determination of suitable material properties from respective CT data, where the traditional approach consists of regression analyses between attenuation-related grey values and mechanical properties. We here present a physics-oriented approach, considering that elasticity and strength of bone tissue originate from the material microstructure and the mechanical properties of its elementary components. Firstly, we reconstruct the linear relation between the clinically accessible grey values making up a CT, and the X-ray attenuation coefficients quantifying the intensity losses from which the image is actually reconstructed. Therefore, we combine X-ray attenuation averaging at different length scales and over different tissues, with recently identified 'universal' composition characteristics of the latter. This gives access to both the normally non-disclosed X-ray energy employed in the CT-device and to in vivo patient-specific and location-specific bone composition variables, such as voxel-specific mass density, as well as collagen and mineral contents. The latter feed an experimentally validated multiscale elastoplastic model based on the hierarchical organization of bone. Corresponding elasticity maps across the organ enter a finite element simulation of a typical load case, and the resulting stress states are increased in a proportional fashion, so as to check the safety against ultimate material failure. In the young patient investigated, even normal physiological loading is probable to already imply plastic events associated with the hydrated mineral crystals in the bone ultrastructure, while the safety factor against failure is still as high as five. Copyright © 2016 John Wiley & Sons, Ltd.