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1. The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Eects and Inflammatory Cytokines by 1-alpha, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts

   Philips, Neena; Ding, Xinxing; Kandalai, Pranathi; Marte, Ilonka; Krawczyk, Hunter; Richardson, Richard (August 2019, Cosmetics)

   null (Ed.)

   Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation, are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1-alpha, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. With regard to anti-inflammation, vitamin D inhibited expression of Il-1 and IL-8 in UVA-radiated fibroblasts, and stimulated HSP-70 in UVA-radiated and UVB-radiated fibroblasts. Overall, vitamin D is predominantly beneficial in preventing UVA-radiation induced photoaging through the differential regulation of the ECM, HSPs, and inflammatory cytokines, and protective effects on the cellular biomolecules. It is also beneficial in preventing UVB-radiation associated photoaging through the stimulation of cell viability and HSP-70, and the inhibition of cellular oxidative damage, and in preventing intrinsic aging through the stimulation of type I collagen and inhibition of cellular oxidative damage. 

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2. Quantification of age-related changes in the structure and mechanical function of skin with multiscale imaging

   https://doi.org/10.1007/s11357-024-01199-9  

   Woessner, Alan_E; Witt, Nathan_J; Jones, Jake_D; Sander, Edward_A; Quinn, Kyle_P (May 2024, GeroScience)

   Abstract The mechanical properties of skin change during aging but the relationships between structure and mechanical function remain poorly understood. Previous work has shown that young skin exhibits a substantial decrease in tissue volume, a large macro-scale Poisson’s ratio, and an increase in micro-scale collagen fiber alignment during mechanical stretch. In this study, label-free multiphoton microscopy was used to quantify how the microstructure and fiber kinematics of aged mouse skin affect its mechanical function. In an unloaded state, aged skin was found to have less collagen alignment and more non-enzymatic collagen fiber crosslinks. Skin samples were then loaded in uniaxial tension and aged skin exhibited a lower mechanical stiffness compared to young skin. Aged tissue also demonstrated less volume reduction and a lower macro-scale Poisson’s ratio at 10% uniaxial strain, but not at 20% strain. The magnitude of 3D fiber realignment in the direction of loading was not different between age groups, and the amount of realignment in young and aged skin was less than expected based on theoretical fiber kinematics affine to the local deformation. These findings provide key insights on how the collagen fiber microstructure changes with age, and how those changes affect the mechanical function of skin, findings which may help guide wound healing or anti-aging treatments. 

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3. Unraveling the effect of collagen damage on bone fracture using in situ synchrotron microtomography with deep learning

   https://doi.org/10.1038/s43246-022-00296-6  

   Sieverts, Michael; Obata, Yoshihiro; Rosenberg, James L.; Woolley, William; Parkinson, Dilworth Y.; Barnard, Harold S.; Pelt, Daniël M.; Acevedo, Claire (October 2022, Communications Materials)

   Abstract When studying bone fragility diseases, it is difficult to identify which factors reduce bone’s resistance to fracture because these diseases alter bone at many length scales. Here, we investigate the contribution of nanoscale collagen behavior on macroscale toughness and microscale toughening mechanisms using a bovine heat-treatment fragility model. This model is assessed by developing an in situ toughness testing technique for synchrotron radiation micro-computed tomography to study the evolution of microscale crack growth in 3D. Low-dose imaging is employed with deep learning to denoise images while maintaining bone’s innate mechanical properties. We show that collagen damage significantly reduces macroscale toughness and post-yield properties. We also find that bone samples with a compromised collagen network have reduced amounts of crack deflection, the main microscale mechanism of fracture resistance. This research demonstrates that collagen damage at the nanoscale adversely affects bone’s toughening mechanisms at the microscale and reduces the overall toughness of bone. 

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4. Anisotropic fracture toughness of Poorman Schist rocks from EGS Collab Experiment 1 Site

   Ruplinger, C.; O’Connell, R.; Sone, H.; Trzeciak, M.; Wang, H. (January 2020, 54th US Rock Mechanics/Geomechanics Symposium)

   We investigate the mode 1 fracture toughness and its anisotropy of Poorman Schist rocks recovered from the Enhanced Geothermal Systems Collaboration (EGS Collab) Experiment 1 site. The EGS Collab team is conducting a series of intermediate (10-20m) scale stimulation and inter-well flow tests with comprehensive instrumentation and characterization at the Sanford Underground Research Facility to validate existing theories and description of hydraulic fractures propagation and associated fluid flow. An important parameter to constrain is how the fracture toughness varies depending on the orientation of the fracture and the direction of fracture propagation, which may have controls on hydraulic fracture propagation. Fracture toughness relative to foliation orientation was determined through the utilization of Cracked Chevron Notched Brazilian Disk (CCNBD) samples in three different orientations (Divider, Arrester, and Foliation Splitting/Short Transverse). Each sample group contains at least three 25.4 mm diameter and 12.7 mm thick CCNBD samples, one of each sample type. Arrester and Foliation Splitting samples were obtained from the same sub-core while Divider samples were obtained from a separate sub-core obtained in close proximity. We found fracture toughness to be weakest in the Foliation Splitting orientation and strongest in the Divider orientation, similar to findings from anisotropic fracture toughness measured in shale rocks. Our findings on the influence of foliation orientation on fracture toughness are presented here. 

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5. Physiochemical effects of acid exposure on bone composition and function

   https://doi.org/10.1016/j.jmbbm.2023.106304  

   Easson, Margaret; Wong, Stephanie; Moody, Mikayla; Schmidt, Tannin A; Deymier, Alix (February 2024, Journal of the Mechanical Behavior of Biomedical Materials)

   Bone is primarily composed of collagen and apatite, two materials which exhibit a high sensitivity to pH dysregulation. As a result, acid exposure of bone, both clinically and in the laboratory is expected to cause compositional and mechanical changes to the tissue. Clinically, Metabolic acidosis (MA), a condition characterized by a reduced physiological pH, has been shown to have negative implications on bone health, including a decrease in bone mineral density and volume as well as increased fracture risk. The addition of bone-like apatite to ionic solutions such as phosphate buffered saline (PBS) and media has been shown to acidify the solution leading to bone acid exposure. Therefore, is it essential to understand how reduced pH physiochemically affects bone composition and in turn its mechanical properties. This study investigates the specific changes in bone due to physiochemical dissolution in acid. Excised murine bones were placed in PBS solutions at different pHs: a homeostatic pH level (pH 7.4), an acidosis equivalent (pH 7.0), and an extreme acidic solution (pH 5.5). After 5 days, the bones were removed from the solutions and characterized to determine compositional and material changes. We found that bones, without cells, were able to regulate pH via buffering, leading to a decrease in bone mineral content and an increase in collagen denaturation. Both of these compositional changes contributed to an increase in bone toughness by creating a more ductile bone surface and preventing crack propagation. Therefore, we conclude that the skeletal systems' physiochemical response to acid exposure includes multifaceted and spatially variable compositional changes that affect bone mechanics. 

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