Concept: Young's modulus
The requirement for immediate vascularization of engineered dental pulp poses a major hurdle towards successful implementation of pulp regeneration as an effective therapeutic strategy for root canal therapy, especially in adult teeth. Here, we demonstrate a novel strategy to engineer pre-vascularized, cell-laden hydrogel pulp-like tissue constructs in full-length root canals for dental pulp regeneration. We utilized gelatin methacryloyl (GelMA) hydrogels with tunable physical and mechanical properties to determine the microenvironmental conditions (microstructure, degradation, swelling and elastic modulus) that enhanced viability, spreading and proliferation of encapsulated odontoblast-like cells (OD21), and the formation of endothelial monolayers by endothelial colony forming cells (ECFCs). GelMA hydrogels with higher polymer concentration (15% w/v) and stiffness enhanced OD21 cell viability, spreading and proliferation, as well as endothelial cell spreading and monolayer formation. We then fabricated pre-vascularized, full-length, dental pulp-like tissue constructs by dispensing OD21 cell-laden GelMA hydrogel prepolymer in root canals of extracted teeth and fabricating 500 µm channels throughout the root canals. ECFCs seeded into the microchannels successfully formed monolayers and underwent angiogenic sprouting within 7 days in culture. In summary, the proposed approach is a simple and effective strategy for engineering of pre-vascularized dental pulp constructs offering potentially beneficial translational outcomes.
Under high-strain-rate compression (strain rate approximately 10(3) s(-1)), nacre (mother-of-pearl) exhibits surprisingly high fracture strength vis-à-vis under quasi-static loading (strain rate 10(-3) s(-1)). Nevertheless, the underlying mechanism responsible for such sharply different behaviors in these two loading modes remains completely unknown. Here we report a new deformation mechanism, adopted by nacre, the best-ever natural armor material, to protect itself against predatory penetrating impacts. It involves the emission of partial dislocations and the onset of deformation twinning that operate in a well-concerted manner to contribute to the increased high-strain-rate fracture strength of nacre. Our findings unveil that Mother Nature delicately uses an ingenious strain-rate-dependent stiffening mechanism with a purpose to fight against foreign attacks. These findings should serve as critical design guidelines for developing engineered body armor materials.
Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young’s modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing hydrogel substrates with physiologically relevant stiffness to dynamically redirect cell fate in vitro.
Mechanics is an important component in the regulation of cell shape, proliferation, migration and differentiation during normal homeostasis and disease states. Biomaterials that match the elastic modulus of soft tissues have been effective for studying this cell mechanobiology, but improvements are needed in order to investigate a wider range of physicochemical properties in a controlled manner. We hypothesized that polydimethylsiloxane (PDMS) blends could be used as the basis of a tunable system where the elastic modulus could be adjusted to match most types of soft tissue. To test this we formulated blends of two commercially available PDMS types, Sylgard 527 and Sylgard 184, which enabled us to fabricate substrates with an elastic modulus anywhere from 5 kPa up to 1.72 MPa. This is a three order-of-magnitude range of tunability, exceeding what is possible with other hydrogel and PDMS systems. Uniquely, the elastic modulus can be controlled independently of other materials properties including surface roughness, surface energy and the ability to functionalize the surface by protein adsorption and microcontact printing. For biological validation, PC12 (neuronal inducible-pheochromocytoma cell line) and C2C12 (muscle cell line) were used to demonstrate that these PDMS formulations support cell attachment and growth and that these substrates can be used to probe the mechanosensitivity of various cellular processes including neurite extension and muscle differentiation.
BACKGROUND: The treatment planning of spine pathologies requires information on the rigidity and permeability of the intervertebral discs (IVDs). Magnetic resonance imaging (MRI) offers great potential as a sensitive and non-invasive technique for describing the mechanical properties of IVDs. However, the literature reported small correlation coefficients between mechanical properties and MRI parameters. Our hypothesis is that the compressive modulus and the permeability of the IVD can be predicted by a linear combination of MRI parameters. METHODS: Sixty IVDs were harvested from bovine tails, and randomly separated in four groups (in-situ, digested-6h, digested-18h, digested-24h). Multi-parametric MRI acquisitions were used to quantify the relaxation times T1 and T2, the magnetization transfer ratio MTR, the apparent diffusion coefficient ADC and the fractional anisotropy FA. Unconfined compression, confined compression and direct permeability measurements were performed to quantify the compressive moduli and the hydraulic permeabilities. Differences between groups were evaluated from a one way ANOVA. Multi linear regressions were performed between dependent mechanical properties and independent MRI parameters to verify our hypothesis. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. Agglomerative Hierarchical Clustering was performed on the 3 principal components. RESULTS: Multilinear regressions showed that 45 to 80% of the Young’s modulus E, the aggregate modulus in absence of deformation HA0, the radial permeability kr and the axial permeability in absence of deformation k0 can be explained by the MRI parameters within both the nucleus pulposus and the annulus pulposus. The principal component analysis reduced our variables to two principal components with a cumulative variability of 52-65%, which increased to 70-82% when considering the third principal component. The dendograms showed a natural division into four clusters for the nucleus pulposus and into three or four clusters for the annulus fibrosus. CONCLUSIONS: The compressive moduli and the permeabilities of isolated IVDs can be assessed mostly by MT and diffusion sequences. However, the relationships have to be improved with the inclusion of MRI parameters more sensitive to IVD degeneration. Before the use of this technique to quantify the mechanical properties of IVDs in vivo on patients suffering from various diseases, the relationships have to be defined for each degeneration state of the tissue that mimics the pathology. Our MRI protocol associated to principal component analysis and agglomerative hierarchical clustering are promising tools to classify the degenerated intervertebral discs and further find biomarkers and predictive factors of the evolution of the pathologies.
Because of its optical and electrical properties, large surfaces, and compatibility with standard silicon processes, porous silicon is a very interesting material in photovoltaic and microelectromechanical systems technology. In some applications, porous silicon is annealed at high temperature and, consequently, the cylindrical pores that are generated by anodization or stain etching reorganize into randomly distributed closed sphere-like pores. Although the design of devices which involve this material needs an accurate evaluation of its mechanical properties, only few researchers have studied the mechanical properties of porous silicon, and no data are nowadays available on the mechanical properties of sintered porous silicon. In this work we propose a finite element model to estimate the mechanical properties of sintered meso-porous silicon. The model has been employed to study the dependence of the Young’s modulus and the shear modulus (upper and lower bounds) on the porosity for porosities between 0% to 40%. Interpolation functions for the Young’s modulus and shear modulus have been obtained, and the results show good agreement with the data reported for other porous media. A Monte Carlo simulation has also been employed to study the effect of the actual microstructure on the mechanical properties.
ABSTRACT Viscoelastic deformation of the contact volume between adhering bacteria and substratum surfaces plays a role in their adhesion and detachment. Currently, there are no deformation models that account for the heterogeneous structure and composition of bacteria, consisting of a relatively soft outer layer and a more rigid, hard core enveloped by a cross-linked peptidoglycan layer. The aim of this paper is to present a new, simple model to derive the reduced Young’s modulus of the contact volume between adhering bacteria and substratum surfaces based on the relationship between deformation and applied external loading force, measured using atomic force microscopy. The model assumes that contact is established through a cylinder with constant volume and does not require assumptions on the properties and dimensions of the contact cylinder. The reduced Young’s moduli obtained (8 to 47 kPa) and dimensions of the contact cylinders could be interpreted on the basis of the cell surface features and cell wall characteristics, i.e., surfaces that are more rigid (because of either less fibrillation, less extracellular polymeric substance production, or a higher degree of cross-linking of the peptidoglycan layer) had shorter contact cylinders and higher reduced Young’s moduli. Application of an existing Hertz model to our experimental data yielded reduced Young’s moduli that were up to 100 times higher for all strains investigated, likely because the Hertz model pertains to a major extent to the more rigid peptidoglycan layer and not only to the soft outer bacterial cell surface, involved in the bond between a bacterium and a substratum surface. IMPORTANCE The viscoelastic properties of the bond between an adhering bacterium and a substratum surface play a role in determining bacterial detachment. For instance, removal of an oral biofilm proceeds according to a viscoelastic failure model, and biofilm left behind after toothbrushing has been found to possess expanded bond lengths between adhering bacteria due to viscoelastic deformation. Current elastic deformation models are unable to distinguish between the soft outer bacterial cell surface and the hard core of a bacterium, enveloped by a peptidoglycan layer. Therefore, here we present a simple model to calculate the Young’s modulus and deformation of the contact volume between an adhering bacterium and a substratum surface that accounts for the heterogeneous structure of a bacterium.
Friction characteristics with respect to surface topographic orientation were investigated using surfaces of different materials and fabricated with grooves of different scales. Scratching friction tests were conducted using a nano-indentation-scratching system with the tip motion parallel or perpendicular to the groove orientation. Similar friction anisotropy trends were observed for all the surfaces studied, which are (1) under a light load and for surfaces with narrow grooves, the tip motion parallel to the grooves offers higher friction coefficients than does that perpendicular to them, (2) otherwise, equal or lower friction coefficients are found under this motion. The influences of groove size relative to the diameter of the mating tip (as a representative asperity), surface contact stiffness, contact area, and the characteristic stiction length are discussed. The appearance of this friction anisotropy is independent of material; however, the boundary and the point of trend transition depend on material properties.
The prototypical photocatalyst TiO2 exists in different polymorphs, the most common forms are the anatase- and rutile-crystal structures. Generally, anatase is more active than rutile, but no consensus exists to explain this difference. Here we demonstrate that it is the bulk transport of excitons to the surface that contributes to the difference. Utilizing high -quality epitaxial TiO2 films of the two polymorphs we evaluate the photocatalytic activity as a function of TiO2-film thickness. For anatase the activity increases for films up to ~5 nm thick, while rutile films reach their maximum activity for ~2.5 nm films already. This shows that charge carriers excited deeper in the bulk contribute to surface reactions in anatase than in rutile. Furthermore, we measure surface orientation dependent activity on rutile single crystals. The pronounced orientation-dependent activity can also be correlated to anisotropic bulk charge carrier mobility, suggesting general importance of bulk charge diffusion for explaining photocatalytic anisotropies.
Since its discovery, the wetting transparency of graphene, the transmission of the substrate wetting property over graphene coating, has gained significant attention due to its versatility for potential applications. Yet, there have been debates on the interpretation and validity of the wetting transparency. Here, we present a theory taking two previously disregarded factors into account and elucidate the origin of the partial wetting transparency. We show that the liquid bulk modulus is crucial to accurately calculate the van der Waals interactions between the liquid and the surface, and that various wetting states on rough surfaces must be considered to understand a wide range of contact angle measurements that cannot be fitted with a theory considering the flat surface. In addition, we reveal that the wetting characteristic of the substrate almost vanishes when covered by any coating as thick as graphene double layers. Our findings reveal a more complete picture of the wetting transparency of graphene as well as other atomically thin coatings, and can be applied to study various surface engineering problems requiring wettability-tuning.