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Bioreactors allowing culture medium direct-perfusion overcome diffusion limitations associated with static culturing and provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on chondrocytes will depend not only on the culture medium flow rate, but also on the scaffold three-dimensional (3D) micro-architecture. We performed computational fluid-dynamic (CFD) simulations of the flow of culture medium through a 3D porous scaffold, with the aim of predicting the shear stress acting on the cells as a function of parameters that can be set in a tissue-engineering experiment, such as the medium flow rate and the diameter of the perfused scaffold section. We developed two CFD models: the first model (Model 1) was built from micro-computed tomography reconstruction of the actual scaffold geometry, while the second model (Model 2) was based on a simplification of the actual scaffold microstructure. The two models showed comparable results in terms of the distribution of the shear stresses acting on the inner surfaces of the scaffold walls. Models 1 and 2 gave a median shear stress of 3 mPa at a flow rate of 0.5 cm³ min^-1 through a 15 mm diameter scaffold. Our results provide a basis for the completion of more exhaustive quantitative studies to further assess the relationship between perfusion at known micro-fluid dynamic conditions and tissue growth in vitro.

In orthopedics, a currently developed technique for large graft hybrid implants consists of using porous and biocompatible scaffolds seeded with a patient's bone cells. Successful culture in such large implants remains a challenge for biologists, and requires strict control of the physicochemical and mechanical environments achieved by perfusion within a bioreactor for several weeks. This perfusion, with a nutritive fluid carrying solute ingredients, is necessary for the active cells to grow, proliferate, differentiate, and produce extracellular matrices. An understanding and control of these processes, which lead to substrate degradation and extracellular matrix remodeling during the in vitro culture phase, depend widely on the success in the realization of new orthopedic biomaterials. Within this context, the analysis of the interactions between convective phenomena of hydrodynamic origin and chemical reactions of biological order which are associated to these processes is a fundamental challenge in the framework of bone tissue engineering. In order to better account for the different intricate processes taking place in such a sample and to design a relevant experimental protocol leading to the definition of an optimal tissue implant, we propose one- and two-dimensional theoretical models based on transport phenomena in porous active media.

The growth plate is a structure formed of cells called chondrocytes; these are arranged in columns and provide the elongation of bone due to their proliferation and hypertrophy. In each column, we can see chondrocytes in their proliferating state, which are constantly dividing, and in hypertrophic state, which grow in a nearly spherical shape. These cells express different proteins and molecules throughout their half-life and exhibit a special behavior depending on their local mechanical and biochemical environments. This article develops a mathematical model that describes the relationship of geometry, growth by proliferation and hypertrophy, and vascular invasion with biochemical and mechanical factors present during endochondral ossification.

Bones of the murine cranial vault are formed by differentiation of mesenchymal cells into osteoblasts, a process that is primarily understood to be controlled by a cascade of reactions between extracellular molecules and cells. We assume that the process can be modeled using Turing's reaction–diffusion equations, a mathematical model describing the pattern formation controlled by two interacting molecules (activator and inhibitor). In addition to the processes modeled by reaction–diffusion equations, we hypothesize that mechanical stimuli of the cells due to growth of the underlying brain contribute significantly to the process of cell differentiation in cranial vault development. Structural analysis of the surface of the brain was conducted to explore the effects of the mechanical strain on bone formation. We propose a mechanobiological model for the formation of cranial vault bones by coupling the reaction-–diffusion model with structural mechanics. The mathematical formulation was solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data that provide precise three-dimensional (3D) measures of murine cranial geometry and cranial vault bone formation for specific embryonic time points. The results of this study suggest that mechanical strain contributes information to specific aspects of bone formation. Our mechanobiological model predicts some key features of cranial vault bone formation that were verified by experimental observations including the relative location of ossification centers of individual vault bones, the pattern of cranial vault bone growth over time, and the position of cranial vault sutures.

The tumor microenvironment plays a critical role in tumorigenesis and metastasis. As tightly controlled extracellular matrix homeostasis is lost during tumor progression, a dysregulated extracellular matrix can significantly alter cellular phenotype and drive malignancy. Altered physical properties of the tumor microenvironment alter cancer cell behavior, limit delivery and efficacy of therapies, and correlate with tumorigenesis and patient prognosis. The physical features of the extracellular matrix during tumor progression have been characterized; however, a wide range of methods have been used between studies and cancer types resulting in a large range of reported values. Here, we discuss the significant mechanical and structural properties of the tumor microenvironment, summarizing their reported values and clinical impact across cancer type and grade. We attempt to integrate the values in the literature to identify sources of reported differences and commonalities to better understand how aberrant extracellular matrix dynamics contribute to cancer progression. An intimate understanding of altered matrix properties during malignant transformation will be crucial in effectively detecting, monitoring, and treating cancer.

Tumor growth is regulated by a diverse set of extracellular influences, including paracrine crosstalk with stromal partners, and biophysical interactions with surrounding cells and tissues.Studies elucidating the role of physical force and the mechanical properties of the extracellular matrix (ECM) itself as regulators of tumor growth and invasion have been greatly catalyzed by the use of in vitro three-dimensional (3D) tumor models. These systems provide the ability to systematically isolate, manipulate, and evaluate impact of stromal components and extracellular mechanics in a platform that is both conducive to imaging and biologically relevant. However, recognizing that mechanoregulatory crosstalk is bi-directional and fully utilizing these models requires complementary methods for in situ measurements of the local mechanical environment. Here, in 3D tumor/fibroblast co-culture models of pancreatic cancer, a disease characterized by its prominent stromal involvement, we evaluate the use of particle-tracking microrheology to probe dynamic mechanical changes. Using videos of fluorescently labeled polystyrene microspheres embedded in collagen I ECM, we measure spatiotemporal changes in the Brownian motion of probes to report local ECM shear modulus and microheterogeneity. This approach reveals stiffening of collagen in fibroblast co-cultures relative to cultures with cancer cells only, which exhibit degraded ECM with heterogeneous microstructure. We further show that these effects are dependent on culture geometry with contrasting behavior for embedded and overlay cultures. In addition to potential application to screening stroma-targeted therapeutics, this work also provides insight into how the composition and plating geometry impact the mechanical properties of 3D cell cultures that are increasingly widely used in cancer biology.

The pollen tube is a tip growing cell that is able to invade plant tissues in order to accomplish its function — the delivery of sperm cells to the ovule. The pistillar tissues through which the tube has to elongate represent a formidable mechanical obstacle, but it is unknown how much force the growing tube is able to exert, or how mechanical impedance affects its growth behavior. We quantified the invasive force of individual pollen tubes using a microfluidic lab-on-a-chip device featuring a microscopic cantilever. Using finite element method the maximum invasive growth force of the growing pollen tube was determined to be in the microNewton range. Real time monitoring revealed that contact with the mechanical obstacle caused a shift in the peak frequency characterizing the oscillatory behavior of the pollen tube growth rate. This suggests the presence of a feedback-based control mechanism with a mechanical regulatory component.

The tumor microenvironment plays a critical role in tumorigenesis and metastasis. As tightly controlled extracellular matrix homeostasis is lost during tumor progression, a dysregulated extracellular matrix can significantly alter cellular phenotype and drive malignancy. Altered physical properties of the tumor microenvironment alter cancer cell behavior, limit delivery and efficacy of therapies, and correlate with tumorigenesis and patient prognosis. The physical features of the extracellular matrix during tumor progression have been characterized; however, a wide range of methods have been used between studies and cancer types resulting in a large range of reported values. Here, we discuss the significant mechanical and structural properties of the tumor microenvironment, summarizing their reported values and clinical impact across cancer type and grade. We attempt to integrate the values in the literature to identify sources of reported differences and commonalities to better understand how aberrant extracellular matrix dynamics contribute to cancer progression. An intimate understanding of altered matrix properties during malignant transformation will be crucial in effectively detecting, monitoring, and treating cancer.

Tissue engineering is a promising solution to address articular cartilage pathology. The creation of strategies for functional replacement of diseased cartilage relies heavily on the knowledge of the physiology and development of articular cartilage, especially in terms of the influence of biomechanical forces on the tissue. This review will present the current knowledge of biomechanical structure–function relationships of native articular cartilage, and synthesize this knowledge with strategies to engineer the tissue in vitro.

The lung contains both epithelial and mesenchymal cell types. Lung epithelial cells are characteristically localized at the interface between the organism and the environment and have many critical and vital functions such as the fluid balance, barrier protection, particulate clearance, production of both mucus and surfactants, and immune response initiation as well as tissue repair after injury. Lung cells are continuously exposed to mechanical stresses during their development and function. For example, lung epithelial cells are continuously exposed to varying levels of mechanical stresses due to lung’s complex structure and the cyclic deformation of the lung during the respiratory cycle. The normal functions of the lung are maintained under these tightly regulated conditions, and changes in mechanical stresses may profoundly affect different functions of lung cells and therefore the overall lung functions. A major goal of lung mechanobiology is to understand how the mechanical behavior of the lung emerges from its cellular and molecular constituents. The central role of mechanics in the lung function was revealed with the help of the rapid progress in seminal historical developments, including both the identification and characterization of the functions of lung surfactants. In this chapter, we will describe the effects of mechanical factors on lung development, and how the airway peristalsis affects lung development. In addition, we will describe the functional roles of parathyroid hormone-related protein (PTHrP) in lung development and stretch transduction, as well as the functions of extracellular calcium-sensing receptor (CaSR) in fetal lung development.