Micromechanical model of bovine Haversian bone predicts strain amplification through soft interfaces

Context. Recent observations of brown dwarf spectroscopic variability in the infrared infer the presence of patchy cloud cover. Aims. This paper proposes a mechanism for producing inhomogeneous cloud coverage due to the depletion of cloud particles through the Coulomb explosion of dust in atmospheric plasma regions. Charged dust grains Coulomb-explode when the electrostatic stress of the grain exceeds its mechanical tensile stress, which results in grains below a critical radius a < aCoulcrit being broken up. Methods. This work outlines the criteria required for the Coulomb explosion of dust clouds in substellar atmospheres, the effect on the dust particle size distribution function, and the resulting radiative properties of the atmospheric regions. Results. Our results show that for an atmospheric plasma region with an electron temperature of Te = 10 eV (≈ 105 K), the critical grain radius varies from 10-7 to 10-4 cm, depending on the grains’ tensile strength. Higher critical radii up to 10-3 cm are attainable for higher electron temperatures. We find that the process produces a bimodal particle size distribution composed of stable nanoscale seed particles and dust particles with a ≥ aCoulcrit , with the intervening particle sizes defining a region devoid of dust. As a result, the dust population is depleted, and the clouds become optically thin in the wavelength range 0:1 - 10 μm, with a characteristic peak that shifts to higher wavelengths as more sub-micrometer particles are destroyed. Conclusions. In an atmosphere populated with a distribution of plasma volumes, this will yield regions of contrasting radiative properties, thereby giving a source of inhomogeneous cloud coverage. The results presented here may also be relevant for dust in supernova remnants and protoplanetary disks.PostprintPeer reviewe

Epithelial mechanobiology, skin wound healing, and the stem cell niche

AbstractSkin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring

Thiol-gelatin-norbornene bioink for laser‐based high‐definition bioprinting

Two-photon polymerization (2PP) is a lithography-based 3D printing method allowing the fabrication of 3D structures with sub-micrometer resolution. This work focuses on the characterization of gelatin-norbornene (Gel-NB) bioinks which enables the embedding of cells via 2PP. The high reactivity of the thiol-ene system allows 2PP processing of cell-containing materials at remarkably high scanning speeds (1000 mm s(-1)) placing this technology in the domain of bioprinting. Atomic force microscopy results demonstrate that the indentation moduli of the produced hydrogel constructs can be adjusted in the 0.2-0.7 kPa range by controlling the 2PP processing parameters. Using this approach gradient 3D constructs are produced and the morphology of the embedded cells is observed in the course of 3 weeks. Furthermore, it is possible to tune the enzymatic degradation of the crosslinked bioink by varying the applied laser power. The 3D printed Gel-NB hydrogel constructs show exceptional biocompatibility, supported cell adhesion, and migration. Furthermore, cells maintain their proliferation capacity demonstrated by Ki-67 immunostaining. Moreover, the results demonstrate that direct embedding of cells provides uniform distribution and high cell loading independently of the pore size of the scaffold. The investigated photosensitive bioink enables high-definition bioprinting of well-defined constructs for long-term cell culture studies

Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests

Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environment of individual trabeculae retrieved from the vertebrae of beagle dogs treated with alendronate (a BP), raloxifene (a SERM) or without treatments. Identification of material properties was performed with a previously developed rheological model and of mechanical properties via fitting of envelope curves. Additionally, tissue mineral density (TMD) and microdamage formation were analyzed. Alendronate treatment resulted in a higher trabecular tissue stiffness and strength, associated with higher levels of TMD. In contrast, raloxifene treatment caused a higher trabecular toughness, pre-dominantly in the post-yield region. Microdamage formation during testing was not affected by either anti-resorptive treatment regimens. These findings highlight that the improved mechanical behavior of whole bones after anti-resorptive treatment is at least partly caused by improved material properties, with different mechanisms for alendronate and raloxifene. This study further shows the power of performing a mechanical characterization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone

Comparison of the oncolytic activity of a replication‐competent and a replication‐deficient herpes simplex virus 1

In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 d106S with replication-competent T-VEC. High infectious doses of HSV-1 d106S killed melanoma (n = 10), head-and-neck squamous cell carcinoma (n = 11), and chondrosarcoma cell lines (n = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time. HSV-1 d106S and, to a lesser extent T-VEC, triggered caspase-dependent early apoptosis as shown by pan-caspase inhibition and specific induction of caspases 3/7, 8, and 9. HSV-1 d106S induced a higher ratio of apoptosis-inducing infected cell protein (ICP) 0 to apoptosis-blocking ICP6 than T-VEC. T-VEC was oncolytic for an extended period of time as viral replication continued, which could be partially blocked by the antiviral drug aciclovir. High doses of T-VEC, but not HSV-1 d106S, increased interferon-β mRNA as part of the intrinsic immune response. When markers of immunogenic cell death were assessed, ATP was released more efficiently in the context of T-VEC than HSV-1 d106S infection, whereas HMGB1 was induced comparatively well. Overall, the early oncolytic effect on three different tumour entities was stronger with the non-replicative strain, while the replication-competent virus elicited a stronger innate immune response and more pronounced immunogenic cell death

Atomic force microscopy and indentation force measurement of bone

This review is summarizing the results obtained from atomic force microscopy (AFM) and nanoindentation experiments to date. The combination of both techniques is especially powerful. It allows to carefully choose indentation locations as well as the post-hoc analysis of the created indents, and hence the possibility to assess the properties of microstructural elements of bonessue. In addition, AFM has improved our understanding of bone ultrastructure and force spectroscopy experiments have led to the discovery of a molecular self-healing effect of bone that may be based on a small fraction of unstructured proteins. Nanoindentation measurements on bone, pose inherent problems since bone is an anisotropic solid showing elastic, viscoelastic, and time-dependent plastic behavior. Hence, derived parameters such as elastic modulus and hardness are to some extent dependent on measurement protocols. However, the development of extensions to the Oliver-Pharr method, being the most widely used analysis method, as well as novel dynamic testing techniques could improve the situation. Nanoindentation is widely used to study bone tissue and some important principal findings have been reported to date. These are presented here together with specific results from nanoindentation experiments of human and animal bones and tables are presented collating the data that can be found in the literature to dat

Anisotropy of bovine cortical bone tissue damage properties

Bone is a heterogeneous, anisotropic natural composite material. Several studies have measured human cortical bone elastic properties in different anatomical directions and found that the Young's modulus was highest in the longitudinal, followed by the tangential and then by the radial direction. This study compared the Young's modulus, the accumulated microdamage and local strains related to the failure process in these three anatomical directions. Cortical bone samples (?360 ?m×360 ?m) were mechanically tested in three-point bending and concomitantly imaged to assess local strains using digital image correlation technique. The bone whitening effect was used to detect microdamage formation and propagation. No statistically significant difference was found between the Young's modulus of longitudinal (9.4±2.0 GPa) and tangential (9.9±1.8 GPa) bovine bone samples, as opposed to previous findings on human bone samples. The same similarity was found for the whitening values (5000±1900 pix/mm(2) for longitudinal, 5800±2600 pix/mm(2) for tangential) and failure strains (16.8±7.0% for longitudinal, 19.1±3.2% for tangential) as well. However, significantly lower values were observed in the radial samples for Young's modulus (5.92±0.77 GPa), whitening (none or minimal) and failure strain (10.8±3.8%). For strains at whitening onset, no statistically significant difference was seen for the longitudinal (5.1±1.6%) and radial groups (4.2±2.0%), however, the tangential values were significantly greater (7.0±2.4%). The data implies that bovine cortical bone tissue in long bones is designed to withstand higher loads in the longitudinal and tangential directions than in the radial one. A possible explanation of the anisotropy in the mechanical parameters derived here might be the structure of the tissues in the three directions tested