Role Of Mechanical Stimuli Research Articles

Steering cell orientation through light-based spatiotemporal modulation of the mechanical environment

The anisotropic organization of cells and the extracellular matrix (ECM) is essential for the physiological function of numerous biological tissues, including the myocardium. This organization changes gradually in space and time, during disease progression such as myocardial infarction. The role of mechanical stimuli has been demonstrated to be essential in obtaining, maintaining and de-railing this organization, but the underlying mechanisms are scarcely known. To enable the study of the mechanobiological mechanisms involved, in vitro techniques able to spatiotemporally control the multiscale tissue mechanical environment are thus necessary. Here, by using light-sensitive materials combined with light-illumination techniques, we fabricated 2D and 3D in vitro model systems exposing cells to multiscale, spatiotemporally resolved stiffness anisotropies. Specifically, spatial stiffness anisotropies spanning from micron-sized (cellular) to millimeter-sized (tissue) were achieved. Moreover, the light-sensitive materials allowed to introduce the stiffness anisotropies at defined timepoints (hours) after cell seeding, facilitating the study of their temporal effects on cell and tissue orientation. The systems were tested using cardiac fibroblasts (cFBs), which are known to be crucial for the remodeling of anisotropic cardiac tissue. We observed that 2D stiffness micropatterns induced cFBs anisotropic alignment, independent of the stimulus timing, but dependent on the micropattern spacing. cFBs exhibited organized alignment also in response to 3D stiffness macropatterns, dependent on the stimulus timing and temporally followed by (slower) ECM co-alignment. In conclusion, the developed model systems allow improved fundamental understanding of the underlying mechanobiological factors that steer cell and ECM orientation, such as stiffness guidance and boundary constraints.

Mechanobiology of human pisiform formation as a model for endochondral ossification.

The role of mechanical stimuli in promoting endochondral ossification during somatic growth and maturation remains an active area of research. This study employs a pisiform model of endochondral ossification to investigate the potential role of mechanobiological signals in the appearance and development of ossification centers and to develop theoretical applications to the primate basicranium. We constructed finite element models based on the structure of a human pisiform within the flexor carpi ulnaris tendon. The pisiform was assigned initial material properties of hyaline cartilage, and tendon properties were based on in situ observations drawn from the literature. A macaque growth model was used to simulate increased load over time as a function of body mass. A load case of uniaxial tension from the tendon was applied over 208 iterations, to simulate weekly growth over a 4-year span. The mechanical signal was defined as shear stress. Element stresses were evaluated in each iteration, with elements exceeding the yield threshold subsequently assigned a higher elastic modulus to mimic mechanically driven mineralization. Three unique mineralization rates were tested. Regardless of rate, all ossification simulations predict a pisiform with heterogeneous stiffness through alternating periods of material stasis and active mineralization/ossification. Assuming metabolic processes underlying endochondral ossification are similar throughout the body, our model suggests that a mechanical signal alone is an insufficient stimulus in the etiology of bone formation through endochondral ossification. Consequently, given the general validity of the simulation, endochondral ossification cannot be fully explained in terms of mechanical stimuli.

Valvular Endothelial Cell Response to the Mechanical Environment-A Review.

Heart valve leaflets are complex structures containing valve endothelial cells, interstitial cells, and extracellular matrix. Heart valve endothelial cells sense mechanical stimuli, and communicate amongst themselves and the surrounding cells and extracellular matrix to maintain tissue homeostasis. In the presence of abnormal mechanical stimuli, endothelial cell communication is triggered in defense and such processes may eventually lead to cardiac disease progression. This review focuses on the role of mechanical stimuli on heart valve endothelial surfaces-from heart valve development and maintenance of tissue integrity to disease progression with related signal pathways involved in this process.

Ion channel mediated mechanotransduction in immune cells

The immune system performs critical functions to defend against invading pathogens and maintain tissue homeostasis. Immune cells reside within or are recruited to a host of mechanically active tissues throughout the body and, as a result, are exposed to varying types and degrees of mechanical stimuli. Despite their abundance in such tissues, the role of mechanical stimuli in influencing immune cell function and the molecular mechanisms responsible for mechanics-mediated changes are still poorly understood. The recent emergence of mechanically-gated ion channels, particularly Piezo1, has provided an exciting avenue of research within the fields of mechanobiology and immunology. Numerous studies have identified roles for mechanically-gated ion channels in mechanotransduction within various different cell types, with a few recent studies in immune cells. These initial studies provide strong evidence that mechanically-gated ion channels play pivotal roles in regulating the immune system. In this review, we discuss characteristics of ion channel mediated mechanotransduction, review the current techniques used to quantify and visualize ion channel activity in response to mechanical stimuli, and finally we provide an overview of recent studies examining the role of mechanically-gated ion channels in modulating immune cell function.

The Role of Mechanical Regulation in Cartilage Tissue Engineering.

Due to the lack of vascular distribution and the slow metabolism, cartilage tissue cannot repair itself, which remains a huge challenge in cartilage regeneration. Tissue engineering using stem cells appears to be a promising method for cartilage repair. Tissue engineers demonstrated that mechanical stimulation can enhance the quality of engineered cartilage, making it more similar to natural cartilage in structure and function. In this review, we summarize recent studies on the role of mechanical stimuli in chondrogenesis, focusing on the applications of extrinsic mechanical loading and the studies on mechanical properties of biomaterials in cartilage tissue engineering. This review will provide fresh insights into the potential use of mechanical stimuli for clinical use.

Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology.

With the term ‘mechanotransduction’, it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes and morphogenesis in various organs, the response of cells to mechanical cues is now also emerging as a major pathophysiology determinant. Cells of the cardiovascular system are typically exposed to a variety of mechanical stimuli ranging from compression to strain and flow (shear) stress. In addition, these cells can also translate subtle changes in biophysical characteristics of the surrounding matrix, such as the stiffness, into intracellular activation cascades with consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes. Since cellular mechanotransduction has a potential readout on long-lasting modifications of the chromatin, exposure of the cells to mechanically altered environments may have similar persisting consequences to those of metabolic dysfunctions or chronic inflammation. In the present review, we highlight the roles of mechanical forces on the control of cardiovascular formation during embryogenesis, and in the development and pathogenesis of the cardiovascular system.

The role of mechanical stimuli on hedonistic and topographical discrimination of textures

Recognition of texture properties requires sliding contact between finger and object surface. Although it is well known that vibrations stimulate the tactile afferents, the mechanism by which Friction-Induced Vibrations (FIVs) interfere with tactile perception is still unknown. As well, the role of mechanical stimuli on hedonistic feedback from the touched surface is unknown. Correlations between surface features and perception are here examined, while the analysis of the mechanical stimuli, which are the direct elements of activation of the human receptors, is performed. Two different sensory analyses are exploited: hedonistic perception and perception dimension categorization. The analysis of the frequency and amplitude of the FIVs, allowed for explaning the correlations between the perception analyses and the topography characteristics of the samples.

Mechanically Induced Periprosthetic Osteolysis: A Systematic Review.

Peri-prosthetic bone loss can result from chemical, biological, and mechanical factors. Mechanical stimulation via fluid pressure and flow at the bone-implant interface may be a significant cause. Evidence supporting mechanically induced osteolysis continues to grow, but there is no synthesis of published clinical and basic science data. We sought to review the literature on two questions: (1) What published evidence supports the concept of mechanically induced osteolysis? (2) What is the proposed mechanism of mechanically induced osteolysis, and does it differ from that of particle-induced osteolysis? A systematic review was performed of the PubMed and Web of Science databases. Additional relevant articles were recommended by the senior authors based on their expert opinion. Abstracts were reviewed and the manuscripts pertaining to the study questions were read in full. Studies showing support of mechanically induced osteolysis were quantified and findings summarized. We identified 49 articles of experimental design supporting the hypothesis that mechanical stimulation of peri-prosthetic bone from fluid pressure and flow can induce osteolysis. While the molecular mechanisms may overlap with those implicated in particle-induced osteolysis, mechanically induced osteolysis appears to be mediated by distinct and parallel pathways. The role of mechanical stimuli is increasingly recognized in the pathogenesis of peri-prosthetic osteolysis. Current research aims to elucidate the molecular mechanisms to better target therapeutic interventions.

The role of mechanical stimuli in the vascular differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are among the most promising and suitable stem cell types for vascular tissue engineering. Substantial effort has been made to differentiate MSCs towards vascular cell phenotypes, including endothelial cells and smooth muscle cells (SMCs). The microenvironment of vascular cells not only contains biochemical factors that influence differentiation, but also exerts hemodynamic forces, such as shear stress and cyclic strain. Recent evidence has shown that these forces can influence the differentiation of MSCs into endothelial cells or SMCs. In this Commentary, we present the main findings in the area with the aim of summarizing the mechanisms by which shear stress and cyclic strain induce MSC differentiation. We will also discuss the interactions between these mechanical cues and other components of the microenvironment, and highlight how these insights could be used to maintain differentiation.

Role of Mechanical Stimuli in Oral Implantation

Prosthetic implantation has been a prevalent surgical procedure in dentistry. Insertion of dental implant significantly changes local oral conditions and leads to the surrounding bone to remodel to a new morphology. To predict how the bone responds such a biomechanical change, finite element analysis (FEA) based remodeling simulation has proven effective. For a range of mechanical stimuli, which should be used remains controversial arguable? This paper aims to compare how the different mechanical stimuli, including mechostat model (effective strain), daily stress and strain energy density (SED) affect the predictions of bone remodeling.

A New Three-Dimensional Exponential Material Model of the Coronary Arterial Wall to Include Shear Stress Due to Torsion

The biomechanical milieu of the coronary arteries is unique in that they experience mechanical deformations of twisting, bending, and stretching due to their tethering to the epicardial surface. Spatial variations in stresses caused by these deformations could account for the heterogeneity of atherosclerotic plaques within the coronary tree. The goal of this work was to utilize previously reported shear moduli to calculate a shear strain parameter for a Fung-type exponential model of the arterial wall and determine if this single constant can account for the observed behavior of arterial segments under torsion. A Fung-type exponential strain-energy function was adapted to include a torsional shear strain term. The material parameter for this term was determined from previously published data describing the relationship between shear modulus and circumferential stress and longitudinal stretch ratio. Values for the shear strain parameter were determined for three geometries representing the mean porcine left anterior descending coronary artery dimensions plus or minus one standard deviation. Finite element simulation of triaxial biomechanical testing was then used to validate the model. The mean value calculated for the shear strain parameter was 0.0759+/-0.0009 (N=3 geometries). In silico triaxial experiments demonstrated that the shear modulus is directly proportional to the applied pressure at a constant longitudinal stretch ratio and to the stretch ratio at a constant pressure. Shear moduli determined from these simulations showed excellent agreement to shear moduli reported in literature. Previously published models describing the torsional shear behavior of porcine coronary arteries require a total of six independent constants. We have reduced that description into a single parameter in a Fung-type exponential strain-energy model. This model will aid in the estimation of wall stress distributions of vascular segments undergoing torsion, as such information could provide insight into the role of mechanical stimuli in the localization of atherosclerotic plaque formation.

APPLICATION OF BIOMECHANICS TO TISSUE ENGINEERING: A PERSONAL VIEW

Cellular biomechanics is an area of study that is receiving more attention as time progresses. The response of cells to their mechanical environment, including biomechanical stimuli, has far-reaching ramifications for the area of tissue engineering, especially for tissues designed to withstand mechanical loading (e.g. bone, cartilage, tendons and ligaments, and arteries). The effects of mechanical stimuli on cells are only recently being examined, and the potential role of mechanical stimuli in tissue engineering is still one that is largely ignored in the design of tissue engineering scaffolds. The relationship of mechanical properties of scaffolds or of mechanical stimuli to cell behavior is complex, but vital to the development of the field. Also, understanding the complex interplay of form and environment on cells involves an increase in our knowledge of how cells react to their total environment including mechanical stimuli and material properties. In order to improve tissue engineering outcomes, a nexus must be developed between the mechanical, biochemical, and biological studies of cellular behavior, in the context of extremely complex systems.

Bone-Density Changes After Stroke

It has been many years since bone loss and fracture risk were first recognized as serious complications of stroke. Hip fracture is associated with a substantial increase in morbidity and mortality for stroke survivors, and therefore, assessing and maintaining skeletal health after stroke should be an important clinical goal. Recent long-term, prospective studies have illustrated a highly nonuniform pattern of bone changes after stroke. In general, there is significant bone loss on the paretic side, which is greatest in those patients with the most severe functional deficits. In some patients, bone loss in the paretic arm during the first year after stroke is the equivalent of >20 yrs of bone loss in healthy individuals of comparable age. Bone density in the nonparetic upper limb can actually increase after stroke, consistent with an increase in habitual use of the nonparetic hand. Bone density in the paretic lower limb can decrease by >10% in <1 yr, with smaller decreases being typical for the nonparetic lower limb. Despite the recent increase in the number of prospective, longitudinal studies, important questions about bone changes after stroke remain unanswered. Longer-term studies quantifying bone loss for periods of >12 mos poststroke are needed to determine how long excess bone loss continues after stroke. Studies with more subjects and with more varied disability levels are needed to better understand the relationships between functional deficits and bone loss. New metrics are needed to quantify the intensity and duration of physical activity in the upper and lower limbs that are consistent with previous research on the role of mechanical stimuli in bone adaptation. Finally, an assessment of skeletal health and the factors that affect bone quantity and quality should be a standard component in the clinical management of all survivors of stroke.

Occlusal forces promote periodontal healing of transplanted teeth and prevent dentoalveolar ankylosis: an experimental study in rats.

The process of healing periodontal ligaments (PDL) after transplantation has been widely examined, but the mechanism for preventing dentoalveolar ankylosis is still unclear. In this study, we focused on the role of mechanical stimuli in preventing ankylosis using an animal model of tooth transplantation assessed by histologic observation and evaluation of proliferating PDL cells. Five-week-old Sprague-Dawley male rats were divided into occluded and nonoccluded groups. The right maxillary first molars were replanted in both groups, and histologic observations were carried out after one or two weeks. The proliferative activity of PDL cells was also examined by assessing the distribution of 5-bromo-2'-deoxyuridine (BrdU). After two weeks in the nonoccluded group, ankylosis was clearly detected and PDL stricture was obvious, whereas no severe bone or root resorption was observed. On the other hand, the occluded group showed an enlarged and thickened PDL with extensive root resorption, but no ankylosis. Based on these findings, the replanted teeth were given a one-week healing period and then occlusion recovery was assessed, which resulted in decreased ankylosis and root resorption. The proliferative activity of PDL cells in the occluded group was generally higher than in the nonoccluded group. The activity of PDL cells in the recovery group was also higher than that of the nonoccluded group. These results suggest that occlusal stimuli promoted the regeneration of the PDL and prevented dentoalveolar ankylosis, whereas excessive initial force might cause severe root and bone resorption.