Stiffness Gradient Research Articles

Evaluation of Secondary Buckling and Ultimate Strength Behaviour According to Boundary Conditions of Curved Plate Subjected to Compressive Load

This paper analyzed the buckling and ultimate strength characteristics of plate members with curvature, which are essentially used in ships and marine structures, through numerical analysis. Major structural members are affected by rotational velocity depending on the rigidity of structures placed around them, and it is very important to check how this affects buckling and ultimate strength. The aspect ratio of the curved plate was adopted as 2.5, 3.0, and 3.5 to reflect the plate thickness range and high-strength steel characteristics actually used. In the case of no curvature, and in the case of curvature, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, and 45 degrees were considered. Under certain thickness and curvature conditions, secondary buckling occurs and the buckling state of the plate changes rapidly. Therefore, the final strength is evaluated lower than in the case where there is no curvature. Buckling and ultimate strength were high in a clamped condition around the curved plate, and there was no specificity in behavior depending on the aspect ratio change. In the four-side simply supported condition, the in-plane stiffness gradient changes depending on the aspect ratio due to the secondary buckling effect, and this characteristic is a phenomenon that is not considered at all in the existing classification method.

Association between pulse wave velocity and cerebral microbleeds: a systematic review and meta-analysis.

Cerebral microbleeds are associated with events that are among the highest mortality and disability events combined worldwide, as well as with hypertensive vasculopathy. The aim of the present study was to investigate the relationship between a marker of hypertensive vasculopathy, arterial stiffness assessed by pulse wave velocity, and cerebral microbleeds. A systematic review and meta-analysis was performed using PubMed, Scopus, and Web of Science, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Cochrane Collaboration Handbook statements. Data extraction, quality assessment and statistical analyses were performed following pre-established criteria. Twenty-one studies involving 18,436 participants were included. Higher levels of pulse wave velocity were associated with a higher presence of cerebral microbleeds p-OR = 1.26 (95% CI; 1.09-1.45), with considerable heterogeneity; even adjusting for potential confounding variables p-OR = 1.12 (95% CI, 1.05-1.20), with substantial heterogeneity. Only the percentage of women was related to p-OR in the adjusted model. Sensitivity analyses confirmed the robustness of our results. Adjusted models showed publication bias. Higher levels of arterial stiffness are associated with greater presence of cerebral microbleeds. This phenomenon may be caused by damage to the brain under higher blood flow loads, in turn due to age-induced reversal of the stiffness gradient between large and small vessels. As the world's population is undergoing demographic ageing, our results underline the importance of establishing pulse wave velocity as a cardiovascular marker for early screening and delaying the onset of the characteristic signs of both diseases.

Reconfigurable topological gradient metamaterials and potential applications

Elastic topological metamaterials are innovative fields of the fusion of physics and mechanics. Through novel microstructural designs, elastic topological metamaterials provide a pioneering approach to precisely manipulate elastic waves, maintaining robustness and efficiency in wave propagation even within complex environments. Recent advancements in reconfigurability and gradient features have significantly enriched the mechanical phenomena of wave manipulation, broadening the application potential of elastic topological metamaterials. In this study, we design the local resonant phononic crystal, employing a spiral support structure to ensure low-frequency characteristics and adjustable mass for flexible configuration. By utilizing the designed lattices with distinct topological phases, the topological valley edge states are constructed. The frequency and group velocity variation of the topological edge states under different stiffness and mass parameters are analyzed. Furthermore, we further constructed the mass and stiffness gradient metamaterial to analyze the transmission law of elastic waves in topological metamaterials. Additionally, the fluctuation features of the wave transmittance under disordered and impurity defects were discussed, confirming the robustness of waveguides within low-frequency topological metamaterials. Finally, we explored the potential applications of the designed metamaterials in energy localization and low-frequency reconfigurable waveguides. Numerical analysis showed that the topological gradient metamaterials can enhance the vibration energy at a specific interface, and low-frequency bend waveguide paths can be adjusted flexibly by configurable mass. In summary, this paper focuses on the low-frequency and gradient features of elastic topological metamaterials, aiming to unlock their application potential in vibrational energy harvesting, vibration suppression, and information transmission, which accelerate the practical implementation of topological metamaterials.

Aortic-Femoral Stiffness Gradient and Cardiovascular Risk in Older Adults.

The aortic-femoral arterial stiffness gradient, calculated as the ratio of lower-limb pulse-wave velocity (PWV) to central (aortic) PWV, is a promising tool for assessing cardiovascular disease (CVD) risk, but whether it predicts incident CVD is unknown. We examined the association of the aortic-femoral arterial stiffness gradient measures carotid-femoral stiffness gradient (femoral-ankle PWV divided by carotid-femoral PWV) and the heart-femoral stiffness gradient (femoral-ankle PWV divided by heart-femoral PWV), as well as PWV, with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality among 3109 participants of the Atherosclerosis Risk in Communities Study cohort (age, 75±5 years; carotid-femoral PWV, 11.5±3.0 m/s), free of CVD. Cox regression was used to estimate hazard ratios (HR) and 95% CIs. Over a median 7.4-year follow-up, there were 322 cases of incident CVD and 410 deaths. In fully adjusted models, only top quartiles of carotid-femoral stiffness gradient (quartile 4: HR, 1.43 [95% CI, 1.03-1.97]; and quartile 3: HR, 1.49 [95% CI, 1.08-2.05]) and heart-femoral stiffness gradient (quartile 4: HR, 1.77 [95% CI, 1.27-2.48]; and quartile 3: HR, 1.41 [95% CI, 1.00-2.00]) were significantly associated with a greater risk of incident CVD. Only high aortic stiffness in combination with low lower-limb stiffness was significantly associated with incident CVD (HR, 1.46 [95% CI, 1.06-2.02]) compared with the referent low aortic stiffness and high lower-limb stiffness. No PWVs were significantly associated with incident CVD. No exposures were associated with all-cause mortality. The aortic-femoral arterial stiffness gradient may enhance CVD risk assessment in older adults in whom the predictive capacity of traditional risk factors and PWV are attenuated.

Simultaneous Color- and Dose-Controlled Thiol-Ene Resins for Multimodulus 3D Printing with Programmable Interfacial Gradients.

Drawing inspiration from nature's own intricate designs, synthetic multimaterial structures have the potential to offer properties and functionality that exceed those of the individual components. However, several contemporary hurdles, from a lack of efficient chemistries to processing constraints, preclude the rapid and precise manufacturing of such materials. Herein, the development of a photocurable resin comprising color-selective initiators is reported, triggering disparate polymerization mechanisms between acrylate and thiol functionality. Exposure of the resin to UV light (365nm) leads to the formation of a rigid, highly crosslinked network via a radical chain-growth mechanism, while violet light (405nm) forms a soft, lightly crosslinked network via an anionic step-growth mechanism. The efficient photocurable resin is employed in multicolor digital light processing 3D printing to provide structures with moduli spanning over two orders of magnitude. Furthermore, local intensity (i.e., grayscale) control enables the formation of programmable stiffness gradients with ≈150× change in modulus occurring across sharp (≈200µm) and shallow (≈9mm) interfaces, mimetic of the human knee entheses and squid beaks, respectively. This study provides composition-processing-property relationships to inform advanced manufacturing of next-generation multimaterial objects having a myriad of applications from healthcare to education.

Study of cell migration trajectory on two-dimensional continuous stiffness gradient surface edited by grayscale photopolymerization

In native tissues, cells encounter a diverse range of stiffness, which can significantly affect their behavior and function. The ability of cells to sense and respond to these mechanical cues is essential for various physiological processes, including cell migration. Cell migration is a complex process influenced by multiple factors, with substrate stiffness emerging as a critical determinant. This study developed a technique to edit the stiffness of polyacrylamide (PAA) hydrogel substrates by adjusting the grayscale level of a photomask during photopolymerization. By analyzing cell morphologies on the hydrogel, we confirmed the development of a single PAA hydrogel substrate with continuous stiffness gradients. This method was used to explore the correlation between substrate stiffness and cell migration dynamics. The study found that cells typically migrated from softer to stiffer surfaces. When the cells initially located on stiffer surfaces, they were able to travel longer distances. Additionally, a continuous 2D stiffness gradient surface was fabricated to explore how cells migrate on smoother versus steeper stiffness gradients. The results showed that cells tended to migrate more readily on smoother stiffness gradient surfaces compared to steeper ones. This study provides valuable insights into cell migration dynamics on substrates with varying stiffness gradients. The results underscore the importance of the mechanical environment in cancer cell migration and offer promising directions for developing interventions to prevent cancer spread.

Revealing chemistry-structure-function relationships in shark vertebrae across length scales

Shark cartilage presents a complex material composed of collagen, proteoglycans, and bioapatite. In the present study, we explored the link between microstructure, chemical composition, and biomechanical function of shark vertebral cartilage using Polarized Light Microscopy (PLM), Atomic Force Microscopy (AFM), Confocal Raman Microspectroscopy, and Nanoindentation. Our investigation focused on vertebrae from Blacktip and Shortfin Mako sharks. As typical representatives of the orders Carcharhiniformes and Lamniformes, these species differ in preferred habitat, ecological role, and swimming style. We observed structural variations in mineral organization and collagen fiber arrangement using PLM and AFM. In both sharks, the highly calcified corpus calcarea shows a ridged morphology, while a chain-like network is present in the less mineralized intermedialia. Raman spectromicroscopy demonstrates a relative increase of glucosaminocycans (GAGs) with respect to collagen and a decrease in mineral-rich zones, underlining the role of GAGs in modulating bioapatite mineralization. Region-specific testing confirmed that intravertebral variations in mineral content and arrangement result in distinct nanomechanical properties. Local Young's moduli from mineralized regions exceeded bulk values by a factor of 10. Overall, this work provides profound insights into a flexible yet strong biocomposite, which is crucial for the extraordinary speed of cartilaginous fish in the worlds’ oceans. Statement of significanceShark cartilage is a morphologically complex material composed of collagen, sulfated proteoglycans, and calcium phosphate minerals. This study explores the link between microstructure, chemical composition, and biological mechanical function of shark vertebral cartilage at the micro- and nanometer scale in typical Carcharhiniform and Lamniform shark species, which represent different vertebral mineralization morphologies, swimming styles and speeds. By studying the intricacies of shark vertebrae, we hope to lay the foundation for biomimetic composite materials that harness lamellar reinforcement and tailored stiffness gradients, capable of dynamic and localized adjustments during movement.

Hypostomus plecostomus-inspired soft sucker to adsorb slippery tissues: a stabilizing post-valvular cavity and stiffness gradient materials provide excellent adsorption performance

The hard suckers commonly used in surgical operations often cause adsorption extrusion damage to the biological tissue. To tackle this problem, from the perspective of bionics, through in-depth observation and research on the special sucker adsorption process and adsorption mechanism of hypostomus plecostomus (HP), this paper proposes a bionic soft hypostomus plecostomus sucker (BSHPS) with a variable stiffness gradient structure with a good adsorption performance on soft moist irregular biological tissues. The BSHPS comprises a lip disc, a pre-valvular cavity, and a post-valvular cavity. Through the volume changes of the pre- and post-valvular cavities, a pressure difference is generated between the inside and outside of the sucker, enabling the lip disc to remain sealed. The experiments were carried out by an automatic tensile force measurement system equipped with a vacuum pump, and the results showed that in slippery environment, the adsorption performance of the BSHPS is improved by a maximum of 61.9% compared to that in dry environment. On a biological tissue surface, the adsorption force is as high as 13.7765 N. The most important advantage of the proposed BSHPS is that it can be firmly adsorbed the surface of soft moist irregular biological tissues, effectively slowing down or avoiding adsorption extrusion damage to the biological tissue. Therefore, the BSHPS is expected to have good application prospects in modern surgical medicine.

Droplet-based microfluidics for engineering shape-controlled hydrogels with stiffness gradient

Current biofabrication strategies are limited in their ability to replicate native shape-to-function relationships, that are dependent on adequate biomimicry of shape, size and spatial heterogeneity, within cell-laden hydrogels. In this study, a diffusion-based microfluidics platform is presented that meets these needs in a two-step process. In the first step, a hydrogel-precursor solution is dispersed into a continuous oil phase within the microfluidics tubing. By adjusting the dispersed and oil phase flow rates, the physical architecture of hydrogel-precursor phases can be adjusted to generate spherical and plug-like structures, as well as continuous meter-long hydrogel-precursor phases (up to 1.75 m). The second step involves the controlled introduction a small molecule-containing aqueous phase through a T-shaped tube connector to enable controlled small molecule diffusion across the interface of the aqueous phase and hydrogel-precursor. Application of this system is demonstrated by diffusing co-initiator sodium persulfate (SPS) into hydrogel-precursor solutions, where the controlled SPS diffusion into the hydrogel-precursor and subsequent photo-polymerization allows for the formation of unique radial stiffness patterns across the shape- and size-controlled hydrogels, as well as allowing the formation of hollow hydrogels with controllable internal architectures. Mesenchymal stromal cells are successfully encapsulated within hollow hydrogels and hydrogels containing radial stiffness gradient. The cells are observed to respond to the microscale spatial heterogeneity as evidenced by increased cell elongation in softer core regions of the hydrogel as compared to the peripheral stiffer hydrogel regions, as well as stiffness-dependent nuclear accumulation of the yes-associated protein mechano-regulator. Finally, breast cancer cells are found to phenotypically switch in response to stiffness gradients, causing a shift in their ability to aggregate, which may have implications for metastasis. The diffusion-based microfluidics will mimic native shape-to-function relationship and provides a platform to further study the roles of micro- and macroscale architectural features that exist within native tissues.

Comparison of Aerodynamic and Elastic Properties in Tissue and Synthetic Models of Vocal Fold Vibrations.

Three laryngeal models were used to investigate the aerodynamic and elastic properties of vocal fold vibration: cadaveric human, excised canine, and synthetic silicone vocal folds. The aim was to compare the characteristics of these models to enhance our understanding of phonatory mechanisms. Flow and medial glottal wall geometry were acquired via particle image velocimetry. Elastic properties were assessed from force-displacement tests. Relatively, the human larynges had higher fundamental frequency values, while canine and synthetic models exhibited greater flow rates. Canine models demonstrated the highest divergence angles and vertical stiffness gradients followed by the human model, both displaying flow separation vortices during closing. Synthetic models, whose advantage is their accessibility and repeatability, displayed the lowest glottal divergence angles and total circulation values compared to tissue models with no flow separation vortices. The elasticity tests revealed that tissue models showed significant hysteresis and vertical stiffness gradients, unlike the synthetic models. These results underscore the importance of model selection based on specific research needs and highlight the potential of canine and synthetic models for controlled experimental studies in phonation.

Optical coherence tomography quantifies gradient refractive index and mechanical stiffness gradient across the human lens

BackgroundAs a key element of ocular accommodation, the inherent mechanical stiffness gradient and the gradient refractive index (GRIN) of the crystalline lens determine its deformability and optical functionality. Quantifying the GRIN profile and deformation characteristics in the lens has the potential to improve the diagnosis and follow-up of lenticular disorders and guide refractive interventions in the future.MethodsHere, we present a type of optical coherence elastography able to examine the mechanical characteristics of the human crystalline lens and the GRIN distribution in vivo. The concept is demonstrated in a case series of 12 persons through lens displacement and strain measurements in an age-mixed group of human subjects in response to an external (ambient pressure modulation) and an intrinsic (micro-fluctuations of accommodation) mechanical deformation stimulus.ResultsHere we show an excellent agreement between the high-resolution strain map retrieved during steady-state micro-fluctuations and earlier reports on lens stiffness in the cortex and nucleus suggesting a 2.0 to 2.3 times stiffer cortex than the nucleus in young lenses and a 1.0 to 7.0 times stiffer nucleus than the cortex in the old lenses.ConclusionsOptical coherence tomography is suitable to quantify the internal stiffness and refractive index distribution of the crystalline lens in vivo and thus might contribute to reveal its inner working mechanism. Our methodology provides new routes for ophthalmic pre-surgical examinations and basic research.

Comparison of liver stiffness, splenic stiffness and novel hepato-splenic stiffness gradient ratio as a non-invasive predictor of varices in patients with compensated advanced chronic liver disease

Comparison of liver stiffness, splenic stiffness and novel hepato-splenic stiffness gradient ratio as a non-invasive predictor of varices in patients with compensated advanced chronic liver disease

Durotaxis and Antidurotaxis Droplet Motion onto Gradient Gel-Substrates.

The self-sustained motion of fluids on gradient substrates is a spectacular phenomenon, which can be employed and controlled in applications by carefully engineering the substrate properties. Here, we report on a design of a gel substrate with stiffness gradient, which can cause the spontaneous motion of a droplet along (durotaxis) or to the opposite (antidurotaxis) direction of the gradient, depending on the droplet affinity to the substrate. By using extensive molecular dynamics simulations of a coarse-grained model, we find that the mechanisms of the durotaxis and antidurotaxis droplet motion are distinct, require the minimization of the interfacial energy between the droplet and the substrate, and share similarities with those mechanisms previously observed for brush substrates with stiffness gradient. Moreover, durotaxis motion takes place over a wider range of affinities and is generally more efficient (faster motion) than antidurotaxis. Thus, our study points to further possibilities and guidelines for realizing both antidurotaxis and durotaxis motion on the same gradient substrate for applications in microfluidics, energy conservation, and biology.

Controlled Interlayer Binding and Healing Improve the Transverse Properties of Upcycled Disposable Waste Wood.

Recovery and reuse of bulk waste wood are particularly challenging because of usage defects and contaminations. Here, we present a robust and efficient strategy for regenerating used wood veneers into high-performance structural materials through micro/nano interface manipulation. Our approach involves using cellulose-based interlayers to bind together two waste wood plates without an external adhesive by partially dissolving and regenerating the interlayer using a solution of ionic liquids and dimethyl sulfoxide. The mechanical properties of the regenerated wood exceed that of natural wood, displaying over a 16 and 20 times increase in transverse tensile strength and modulus, respectively, and 4-6 times improvement in longitudinal tensile strength and modulus. Nanoscale mechanical analyses show that the improvement is possible as a result of several factors, including the robust network structure of the interlayer, the good adhesion at the wood-interlayer interface, the compacted wood structure, and the low stiffness and deformation gradients between the interlayer and the wood structure. The interlayers can be created from waste papers and wood particles by taking advantage of the nanofibrillar structure of cellulose.

A fibronectin gradient remodels mixed-phase mesoderm.

Physical processes ultimately shape tissue during development. Two emerging proposals are that cells migrate toward stiffer tissue (durotaxis) and that the extent of cell rearrangements reflects tissue phase, but it is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally, or intercalate as a function of their location along a stiffness gradient. A modified Landau phase equation that incorporates tissue stiffness accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by WNT5A-YAP feedback that controls cell movements, tissue shape, and skeletal pattern. The results identify a key determinant of phase transition and show how fibronectin-dependent directional cell movement emerges in a mixed-phase environment in vivo.

Serum Myostatin is Associated With Central-to-Peripheral Arterial Stiffness Gradient in Healthy Adolescents: The MACISTE Study.

Myostatin is a protein compound, structurally related to the transforming growth factor-beta protein, which plays a pivotal role in regulating muscle growth and extracellular matrix production. It exerts both profibrotic and antihypertrophic effects on vascular smooth muscle cells. Aim of the study was to explore the potential association between serum myostatin levels (sMSTN) and carotid-femoral pulse wave velocity (cf-PWV), carotid-radial pulse wave velocity (cr-PWV), and their ratio (PWVr), in a cohort of healthy adolescents. A cohort of 128 healthy subjects (mean age 17 ± 2 years, 59% male) was randomly selected from participants to the MACISTE (Metabolic And Cardiovascular Investigation at School, TErni) study. sMSTN was assessed utilizing an enzyme-linked immunosorbent assay. PWVs were measured in the supine position using high-fidelity applanation tonometry. The mean cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s, and PWVr was 0.75 ± 0.12. PWVr exhibited a linear increase across increasing quartiles of sMSTN (0.71 ± 0.1, 0.74 ± 0.1, 0.7 ± 0.1, 0.77 ± 0.1, P for trend = 0.03), whereas the association between sMSTN and each single component of PWVr (cf-PWV, cr-PWV) did not attain statistical significance. Quartiles of sMSTN displayed a positive trend with serum HDL-cholesterol (P = 0.01) and a negative one with LDL-cholesterol (P = 0.01). In a multivariate linear model, the association between PWVr and sMSTN was independent of SBP values, age, sex, heart rate, BMI, HDL-cholesterol, and HOMA Index. In healthy adolescents, sMSTN showed independent associations with PWVr, a measure of central-to-peripheral arterial stiffness gradient. sMSTN may exert differential effects on the structural and functional properties of the arterial wall.

Unraveling the orientation-dependent mechanics of dental enamel in the red-necked wallaby

Dental enamels of different species exhibit a wide variety of microstructural patterns that are attractive to mimic in bioinspired composites to simultaneously achieve high stiffness and superior toughness. Non-human enamel types, however, have not yet received the deserved attention and their mechanical behaviour is largely unknown. Using nanoindentation tests and finite element modelling, we investigate the mechanical behaviour of Macropus rufogriseus enamel, revealing a dominating influence of the microstructure on the effective mechanical behaviour and allowing insight into structural dependencies. We find a shallow gradient in stiffness and low degree of anisotropy over the enamel thickness that is attributed to the orientation and size of microstructural features. Most notably, M. rufogriseus’s modified radial enamel has a far simpler structural pattern than other species’, but achieves great property amplification. It is therefore a very promising template for biomimetic design. Statement of significanceThe diversity of dental enamel structures in different species is well documented, but the mechanical behaviour of non-human enamel types is largely unknown. In this work, we investigate the microstructure and structure-dependent mechanical properties of marsupial enamel by nanoindentation and finite element simulations. Combining these methods gives valuable insights into the performance of modified radial enamel structures. Their stiffness and toughness stems from a unique structural design that is far less complex than well-studied human enamel types, which makes it a uniquely suitable template for biomimetic design.

Modeling and analysis of gradient metamaterials for broad fusion bandgaps

A gradient metamaterial with varying-stiffness local resonators is proposed to open the multiple bandgaps and further form a broad fusion bandgap. First, three local resonators with linearly increasing stiffness are periodically attached to the spring-mass chain to construct the gradient metamaterial. The dispersion relation is then derived based on Bloch’s theorem to reveal the fusion bandgap theoretically. The dynamic characteristic of the finite spring-mass chain is investigated to validate the fusion of multiple bandgaps. Finally, the effects of the design parameters on multiple bandgaps are discussed. The results show that the metamaterial with a non-uniform stiffness gradient pattern is capable of opening a broad fusion bandgap and effectively attenuating the longitudinal waves within a broad frequency region.

Effective boundary conditions for second-order homogenization

Using matched asymptotic expansions, we derive an equivalent bar model for a periodic, one-dimensional lattice made up of linear elastic springs connecting both nearest and next-nearest neighbors. We obtain a strain-gradient model with effective boundary conditions accounting for the boundary layers forming at the endpoints. It is accurate to second order in the scale separation parameter ɛ≪1, as shown by a comparison with the solution to the discrete lattice problem. The homogenized modulus associated with the gradient effect (gradient stiffness) is found negative, as is often the case in second-order homogenization. Negative gradient stiffnesses are widely viewed as paradoxical as they can induce short-wavelength oscillations in the homogenized solution. In the one-dimensional lattice, the asymptotically correct boundary conditions are shown to suppress the oscillations, thereby restoring consistency. By contrast, most of the existing work on second-order homogenization makes use of postulated boundary conditions which, we argue, not only ruin the order of the approximation but are also the root cause of the undesirable oscillations.

A review of the effects of extracellular matrix stiffness on cellular activity

The extracellular matrix is a vital component of a cellular system. It is responsible for several metabolic processes within cells and its properties can have major effects on cellular activity. Recent research has begun to understand the role of physical interactions between the matrix and the cell on cellular growth and repair. In this work, we review the role of the stiffness of the extracellular matrix in determining cellular activity. We first review the effect on stem cell differentiation through the influence of cytoskeletal feedback loops and induced traction stresses. We then discuss the effects of metabolic reprogramming in tumor progression via molecular upregulation of YAP/TAZ and genetic expression. Finally, we highlight the effects of the stiffness gradient dictated by durotaxis and induced hypoxia on the rate of tumor progression. We hope this review sheds light on the major impact that the extracellular matrix has on various biological activities.