21 research outputs found
Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds
The application of three-dimensional (3D) biomaterials
to facilitate the adhesion, proliferation, and differentiation
of cells has been widely studied for tissue engineering
purposes. The fabrication methods used to improve the
mechanical response of the scaffold produce complex and
non regular structures. Apart from the mechanical aspect, the
fluid behavior in the inner part of the scaffold should also be
considered. Parameters such as permeability (k) or wall shear
stress (WSS) are important aspects in the provision of
nutrients, the removal of metabolic waste products or the
mechanically-induced differentiation of cells attached in the
trabecular network of the scaffolds. Experimental measurements
of these parameters are not available in all labs.
However, fluid parameters should be known prior to other
types of experiments. The present work compares an
experimental study with a computational fluid dynamics
(CFD) methodology to determine the related fluid parameters
(k and WSS) of complex non regular poly(L-lactic acid)
scaffolds based only on the treatment of microphotographic
images obtained with a microCT (lCT). The CFD analysis
shows similar tendencies and results with low relative
difference compared to those of the experimental study, for
high flow rates. For low flow rates the accuracy of this
prediction reduces. The correlation between the computational
and experimental results validates the robustness of the
proposed methodology.The authors gratefully acknowledge research support from the Spanish Ministry of Science and Innovation through research project DPI2010-20399-C04-01. The Instituto de Salud Carlos III (ISCIII) through the CIBER initiative and the Platform for Biological Tissue Characterization of the Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN) are also gratefully acknowledged.Acosta Santamaría, VA.; Malvé, M.; Duizabo, A.; Mena Tobar, A.; Gallego Ferrer, G.; García Aznar, J.; Doblare Castellano, M.... (2013). Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds. Annals of Biomedical Engineering. 41(11):2367-2380. https://doi.org/10.1007/s10439-013-0849-8S236723804111Acosta Santamaría, V., H. Deplaine, D. Mariggió, A. R. Villanueva-Molines, J. M. García-Aznar, J. L. Gómez Ribelles, M. Doblaré, G. Gallego Ferrer, and I. Ochoa. Influence of the macro and micro-porous structure on the mechanical behavior of poly(l-lactic acid) scaffolds. J. Non-Cryst. Solids 358(23):3141–3149, 2012.Adachi, T., Y. Osako, M. Tanaka, M. Hojo, and S. J. Hollister. Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration. Biomaterials 27(21):3964–3972, 2006.Adamczyk, Z., and T. G. M. Vandeven. Deposition of particles under external forces in laminar-flow through parallel-plate and cylindrical channels. J. Colloid Interface Sci. 80(2):340–356, 1981.Alberich, B. A., D. Moratal, J. L. Escobar, J. C. Rodríguez, A. Vallés-Lluch, L. Martí-Bonmatí, et al. Microcomputed tomography and microfinite element modeling for evaluating polymer scaffolds architecture and their mechanical properties. J. Biomed. Mater. Res. B Appl. Biomater. 91B(1):191–202, 2009.Al-Munajjed, A., M. Hien, R. Kujat, J. P. Gleeson, and J. Hammer. Influence of pore size on tensile strength, permeability and porosity of hyaluronan-collagen scaffolds. J. Mater. Sci. Mater. Med. 19(8):2859–2864, 2008.Alves da Silva, M. L., A. Martins, A. R. Costa-Pinto, V. M. Correlo, P. Sol, M. Bhattacharya, S. Faria, R. L. Reis, and N. M. Neves. Chondrogenic differentiation of human bone marrow mesenchymal stem cells in chitosan-based scaffolds using a flow-perfusion bioreactor. J. Tissue Eng. Regen. Med. 5(9):722–732, 2011.Ansys (2010) CFX Theory User Manual. Canonsburg, PA: Ansys Software.Brígido, R. D., J. M. Estellés, J. A. Sanz, J. M. García-Aznar, and M. S. Sánchez. Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: fabrication, mechanical properties, and finite element modeling. J. Biomed. Mater. Res. B Appl. Biomater. 81B(2):448–455, 2007.Byrne, P. D., D. Lacroix, J. A. Planell, D. J. Kelly, and P. J. Prendergast. Simulation of tissue differentiation in a scaffold as a function of porosity, Young’s modulus and dissolution rate: application of mechanobiological models in tissue engineering. Biomaterials 28:5544–5554, 2007.Chor, M. V., and W. Li. A permeability measurement system for tissue engineering scaffolds. Meas. Sci. Technol. 18(1):208–216, 2007.Cozensroberts, C., J. A. Quinn, and D. A. Lauffenburger. Receptor-mediated adhesion phenomena—model studies with the radial-flow detachment assay. Biophys. J. 58(1):107–125, 1990.Davisson, T., R. L. Sah, and A. Ratcliffe. Perfusion increases cell content and matrix synthesis in chondrocyte three-dimensional cultures. Tissue Eng. 8(5):807–816, 2002.Deplaine, H., M. Lebourg, P. Ripalda, A. Vidaurre, P. Sanz-Ramos, G. Mora, F. Prósper, I. Ochoa, M. Doblaré, J. L. Gómez Ribelles, I. Izal-Azcárate, and G. Gallego Ferrer. Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(l-lactic acid) scaffolds. J. Biomed. Mater. Res. B Appl. Biomater. 101(1):173–186, 2013.Dias, M. R., P. R. Fernandes, J. M. Guedes, and S. J. Hollister. Permeability analysis of scaffolds for bone tissue engineering. J. Biomech. 45(6):938–944, 2012.Freyman, T. M., I. V. Yannas, and L. J. Gibson. Cellular materials as porous scaffolds for tissue engineering. Prog. Mater Sci. 46:273–282, 2001.Gong, S., H. Wang, Q. Sun, S. T. Xue, and J. Wang. Mechanical properties and in vitro biocompatibility of porous zein scaffolds. Biomaterials 27(20):3793–3799, 2006.Gutierrez, R. A., and E. T. Crumpler. Potential effect of geometry on wall shear stress distribution across scaffold surfaces. Ann. Biomed. Eng. 36(1):77–85, 2008.Hammer, D. A., and D. Lauffenburger. A dynamic-model for receptor-mediated cell adhesion to surfaces. Biophys. J. 52(3):475–487, 1987.Ho, S. T., and D. W. Hutmacher. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials 27(8):1362–1376, 2006.Ho, M. H., P. Y. Kuo, H. J. Hsieh, T. Y. Hsien, L. T. Hou, J. Y. Lai, and D. M. Wang. Preparation of porous scaffolds by using freeze-extraction and freeze-gelation methods. Biomaterials 25(1):129–138, 2004.Hutmacher, D. W., J. T. Schantz, C. X. Lam, K. C. Tan, and T. C. Lim. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J. Tissue Eng. Regen. Med. 1(4):245–260, 2007.Izal, I., P. Aranda, P. Sanz-Ramos, P. Ripalda, G. Mora, F. Granero-Moltó, H. Deplaine, J. L. Gómez-Ribelles, G. G. Ferrer, V. Acosta, I. Ochoa, J. M. García-Aznar, E. J. Andreu, M. Monleón-Pradas, M. Doblaré, and F. Prósper. Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage. Knee Surg. Sports Traumatol. Arthrosc., 2012.Kapur, S., D. J. Baylink, and K. H. Lau. Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32(3):241–251, 2003.Karande, T. S., J. L. Ong, and C. M. Agrawal. Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, architecture, and nutrient mixing. Ann. Biomed. Eng. 32(12):1728–1743, 2004.Kelly, D. J., and P. J. Prendergast. Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects. J. Biomech. 38(7):1413–1422, 2005.Kreke, M. R., L. A. Sharp, Y. W. Lee, and A. S. Goldstein. Effect of intermittent shear stress on mechanotransductive signaling and osteoblastic differentiation of bone marrow stromal cells. Tissue Eng. Part A 14(4):529–537, 2008.Lacroix, D., A. Chateau, M. P. Ginebra, and J. A. Planell. Micro-finite element models of bone tissue-engineering scaffolds. Biomaterials 27(30):5326–5334, 2006.Lacroix, D., and P. J. Prendergast. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J. Biomech. 35(9):1163–1171, 2002.Li, S., J. R. De Wijn, J. Li, P. Layrolle, and K. De Groot. Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio. Tissue Eng. 9:535–548, 2003.Melchels, F. P. W., B. Tonnarelli, A. L. Olivares, I. Martin, D. Lacroix, J. Feijen, et al. The influence of the scaffold design on the distribution of adhering cells after perfusion cell seeding. Biomaterials 32(11):2878–2884, 2011.O’Brien, F. J., B. A. Harley, M. A. Waller, I. Yannas, L. J. Gibson, and P. Prendergast. The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering. Technol. Health Care 15(1):3–17, 2007.Ochoa, I., J. A. Sanz, J. M. Garcia-Aznar, M. Doblare, D. M. Yunos, and A. R. Boccaccini. Permeability evaluation of 45S5 bioglass-based scaffolds for bone tissue engineering. J. Biomech. 42:257–260, 2009.Porter, B., R. Zauel, H. Stockman, R. Guldberg, and D. Fyhrie. 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. Mater. Res. 38:543–549, 2005.Sandino, C., S. Checa, P. J. Prendergast, and D. Lacroix. Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive strains using a lattice modeling approach. Biomaterials 31(8):2446–2452, 2010.Sanz, J. A., J. M. García-Aznar, and M. Doblaré. On scaffold designing for bone regeneration: a computational multiscale approach. Acta Biomater. 5(1):219–229, 2009.Sanz, J. A., C. Kasper, M. van Griensven, J. M. Garcia-Aznar, I. Ochoa, and M. Doblare. Mechanical and flow characterization of Sponceram® carriers: evaluation by homogenization theory and experimental validation. J. Biomed. Mater. Res. B Appl. Biomater. 87B(1):42–48, 2008.Singh, H., S. H. Teoh, H. T. Low, and D. W. Hutmacher. Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation. J. Biotechnol. 119:181–196, 2005.Sjollema, J., and H. J. Busscher. Deposition of polystyrene latex-particles toward polymethylmethacrylate in a parallel plate flow cell. J. Colloid Interface Sci. 132(2):382–394, 1989.Truscello, S., G. Kerckhofs, S. Van Bael, G. Pyka, J. Schrooten, and H. Van Oosterwyck. Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study. Acta Biomater. 8(4):1648–1658, 2012.Woodfield, T. B., J. Malda, J. Wijn, F. Péters, J. Riesle, and C. A. van Blitterswijk. Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique. Biomaterials 25(18):4149–4161, 2004
GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways
Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Evaluation of appendicitis risk prediction models in adults with suspected appendicitis
Background
Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis.
Methods
A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis).
Results
Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent).
Conclusion
Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified
Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU
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Mechanical behavior of carbon-reinforced thermoplastic sandwich composites with several core types during three-point bending tests
International audienc
Model reduction methodology for computational simulations of endovascular repair
International audienceEndovascular aneurysm repair (EVAR) is a current alternative treatment for thoracic and abdominal aortic aneurysms, but is still sometimes compromised by possible complications such as device migration or endoleaks. In order to assist clinicians in preventing these complications, finite element analysis (FEA) is a promising tool. However, the strong material and geometrical nonlinearities added to the complex multiple contacts result in costly finite-element models. To reduce this computational cost, we establish here an alternative and systematic methodology to simplify the computational simulations of stent-grafts (SG) based on FEA. The model reduction methodology relies on equivalent shell models with appropriate geometrical and mechanical parameters. It simplifies significantly the contact interactions but still shows very good agreement with a complete reference finite-element model. Finally, the computational time for EVAR simulations is reduced of a factor 6 to 10. An application is shown for the deployment of a SG during thoracic endovascular repair, showing that the developed methodology is both effective and accurate to determine the final position of the deployed SG inside the aneurysm