On the preservation of fibre direction during axisymmetric hyperelastic mass-growth of a finite fibre-reinforced tube

Several types of tube-like fibre-reinforced tissue, including arteries and veins, different kinds of muscle, biological tubes as well as plants and trees, grow in an axially symmetric manner that preserves their own shape as well as the direction and, hence, the shape of their embedded fibres. This study considers the general, three-dimensional, axisymmetric mass-growth pattern of a finite tube reinforced by a single family of fibres growing with and within the tube, and investigates the influence that the preservation of fibre direction exerts on relevant mathematical modelling, as well on the physical behaviour of the tube. Accordingly, complete sets of necessary conditions that enable such axisymmetric tube patterns to take place are initially developed, not only for fibres preserving a general direction, but also for all six particular cases in which the fibres grow normal to either one or two of the cylindrical polar coordinate directions. The implied conditions are of kinematic character but are independent of the constitutive behaviour of the growing tube material. Because they hold in addition to, and simultaneously with standard kinematic relations and equilibrium equations, they describe growth by an overdetermined system of equations. In cases of hyperelastic mass-growth, the additional information they thus provide enable identification of specific classes of strain energy densities for growth that are admissible and, therefore, suitable for the implied type of axisymmetric tube mass-growth to take place. The presented analysis is applicable to many different particular cases of axisymmetric mass-growth of tube-like tissue, though admissible classes of relevant strain energy densities for growth are identified only for a few example applications. These consider and discuss cases of relevant hyperelastic mass-growth which (i) is of purely dilatational nature, (ii) combines dilatational and torsional deformation, (iii) enables preservation of shape and direction of helically growing fibres, as well as (iv) plane fibres growing on the cross-section of an infinitely long fibre-reinforced tube. The analysis can be extended towards mass-growth modelling of tube-like tissue that contains two or more families of fibres. Potential combination of the outlined theoretical process with suitable data obtained from relevant experimental observations could lead to realistic forms of much sought strain energy functions for growth

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

Mechanical Strain Stabilizes Reconstituted Collagen Fibrils against Enzymatic Degradation by Mammalian Collagenase Matrix Metalloproteinase 8 (MMP-8)

Collagen, a triple-helical, self-organizing protein, is the predominant structural protein in mammals. It is found in bone, ligament, tendon, cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently postulated that fibrillar collagens (and their complementary enzymes) comprise the basis of a smart structural system which appears to support the retention of molecules in fibrils which are under tensile mechanical strain. The theory suggests that the mechanisms which drive the preferential accumulation of collagen in loaded tissue operate at the molecular level and are not solely cell-driven. The concept reduces control of matrix morphology to an interaction between molecules and the most relevant, physical, and persistent signal: mechanical strain.The investigation was carried out in an environmentally-controlled microbioreactor in which reconstituted type I collagen micronetworks were gently strained between micropipettes. The strained micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and relative degradation rates for loaded and unloaded fibrils were tracked simultaneously using label-free differential interference contrast (DIC) imaging. It was found that applied tensile mechanical strain significantly increased degradation time of loaded fibrils compared to unloaded, paired controls. In many cases, strained fibrils were detectable long after unstrained fibrils were degraded.In this investigation we demonstrate for the first time that applied mechanical strain preferentially preserves collagen fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8. These results have the potential to contribute to our understanding of many collagen matrix phenomena including development, adaptation, remodeling and disease. Additionally, tissue engineering could benefit from the ability to sculpt desired structures from physiologically compatible and mutable collagen

Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

[EN] In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.The authors acknowledge the Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46641-R and to the Generalitat Valenciana for Programme PROMETEO 2016/007. The authors declare that they have no conflict of interestVercher Martínez, A.; Giner Maravilla, E.; Belda, R.; Aigoun, A.; Fuenmayor Fernández, F. (2018). Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach. Biomechanics and Modeling in Mechanobiology. 17(2):449-464. https://doi.org/10.1007/s10237-017-0971-xS449464172Akiva U, Wagner HD, Weiner S (1998) Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone. J Mater Sci 33:1497–1509Ascenzi A, Bonucci E (1967) The tensile properties of single osteons. Ana Rec 158:375–386Barbour KE, Zmuda JM, Strotmeyer ES, Horwitz MJ, Boudreau R, Evans RW, Ensrud K, Petit MA, Gordon CL, Cauley JA (2013) Correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia older men: the osteoporotic fractures in men study. 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MMTV-Wnt1 and -ΔN89β-Catenin Induce Canonical Signaling in Distinct Progenitors and Differentially Activate Hedgehog Signaling within Mammary Tumors

Canonical Wnt/β-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-ΔN89β-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin activate canonical Wnt signaling within distinct cell-types. ΔN89β-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18+ER−PR−CD24highCD49flow profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14+/p63+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-ΔN89β-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand

CD44(+)/CD24(- )breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis

INTRODUCTION: A subpopulation (CD44(+)/CD24(-)) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. METHODS: CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. RESULTS: Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44(+)/CD24(- )cells. Cell lines with high CD44(+)/CD24(- )cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44(+)/CD24(- )population than in other cell lines. Among the CD44(+)/CD24(-)-positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44(+)/CD24(- )subpopulation were more invasive than other cell lines. However, only a subset of CD44(+)/CD24(-)-positive cell lines was able to home and proliferate in lungs. CONCLUSION: Breast cancer cells with CD44(+)/CD24(- )subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis

Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 2:Rotator Cuff

Rotator cuff tears are common and result in considerable morbidity. Tears within the tendon substance or at its insertion into the humeral head represent a considerable clinical challenge because of the hostile local environment that precludes healing. Tears often progress without intervention, and current surgical treatments are inadequate. Although surgical implants, instrumentation, and techniques have improved, healing rates have not improved, and a high failure rate remains for large and massive rotator cuff tears. The use of biologic adjuvants that contribute to a regenerative microenvironment have great potential for improving healing rates and function after surgery. This article presents a review of current and emerging biologic approaches to augment rotator cuff tendon and muscle regeneration focusing on the scientific rationale, preclinical, and clinical evidence for efficacy, areas for future research, and current barriers to advancement and implementation

The determinants and consequences of adult nursing staff turnover: a systematic review of systematic reviews.

BACKGROUND: Nurses leaving their jobs and the profession are an issue of international concern, with supply-demand gaps for nurses reported to be widening. There is a large body of existing literature, much of which is already in review form. In order to advance the usefulness of the literature for nurse and human resource managers, we undertook an overview (review of systematic reviews). The aim of the overview was to identify high quality evidence of the determinants and consequences of turnover in adult nursing. METHODS: Reviews were identified which were published between 1990 and January 2015 in English using electronic databases (the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, Applied Social Sciences Index and Abstracts, CINAHL plus and SCOPUS) and forward searching. All stages of the review were conducted in parallel by two reviewers. Reviews were quality appraised using the Assessment of Multiple Systematic Reviews and their findings narratively synthesised. RESULTS: Nine reviews were included. We found that the current evidence is incomplete and has a number of important limitations. However, a body of moderate quality review evidence does exist giving a picture of multiple determinants of turnover in adult nursing, with - at the individual level - nurse stress and dissatisfaction being important factors and -at the organisational level - managerial style and supervisory support factors holding most weight. The consequences of turnover are only described in economic terms, but are considered significant. CONCLUSIONS: In making a quality assessment of the review as well as considering the quality of the included primary studies and specificity in the outcomes they measure, the overview found that the evidence is not as definitive as previously presented from individual reviews. Further research is required, of rigorous research design, whether quantitative or qualitative, particularly against the outcome of actual turnover as opposed to intention to leave. TRIAL REGISTRATION: PROSPERO Registration 17 March 2015: CRD42015017613