Influence of the heat treatment on the particles size and on the crystalline phase of TiO2 synthesized by the sol-gel method

Titanium biomaterials' response has been recognized to be affected by particles size, crystal structure, and surface properties. Chemical and structural properties of these nanoparticle materials are important, but their size is the key aspect. The aim of this study is the synthesis of TiO2 nanoparticles by the sol-gel method, which is an ideal technique to prepare nanomaterials at low temperature. The heat treatment can affect the structure of the final product and consequently its biological properties. For this reason, the chemical structure of the TiO2 nanoparticles synthesized was investigated after each heat treatment, in order to evaluate the presence of different phases formed among the nanoparticles. FTIR spectroscopy and XRD have been used to evaluate the different structures. The results of these analyses suggest that an increase of the calcination temperature induces the formation of mixed-crystalline-phases with different content of anatase and rutile phases. The results obtained by SEM measurements suggest that an increase in the particles size accompanied by a noticeable aggregation of TiO2 nanoparticles is due to high temperatures achieved during the thermal treatments and confirmed the presence of different content of the two crystalline phases of titanium dioxide

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78125/1/ten.teb.2009.0340.pd

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Nonlinear modeling of venous leg ulcer healing rates

<p>Abstract</p> <p>Background</p> <p>The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.</p> <p>Methods</p> <p>We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.</p> <p>Results</p> <p>A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.</p> <p>Conclusion</p> <p>We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.</p

<i>Besnoitia besnoiti</i> among cattle in insular and northwestern Italy: endemic infection or isolated outbreaks?

Background: Bovine besnoitiosis, caused by the apicomplexan Besnoitia besnoiti, is a chronic and debilitating disease considered as emerging in Europe. In Spain, Portugal and France it is endemic and foci of infection were recorded in Germany, Switzerland, Hungary, Greece and Italy. In Italy, cases of bovine besnoitiosis were registered both in imported and autochthonous cattle, and mostly in central regions; high seroprevalence was also revealed by an epidemiological survey performed in the southern part of the country. Aiming to update information on the disease in northwestern and insular areas of Italy, where data on bovine besnoitiosis were missing, a serosurvey was designed for the present study. Methods: Three thousand one hundred and forty bovine blood samples from both dairy and beef farms (n = 126) were collected in northwestern regions (Lombardy, Piedmont and Liguria) and in the island of Sardinia. Samples were analyzed by a standardized in-house ELISA and those resulted positive were re-tested by Western Blot (WB) for confirmation. On results obtained by both ELISA and WB, apparent (AP) and true prevalence (TP) were calculated at individual and herd levels. Further, a panel of sera resulted positive to ELISA was analyzed by IFAT. Results: A total of 712 animals (AP = 22.7%; TP = 18.8%) and 109 farms (AP = 86.5%; TP = 88.2%) showed a positive reaction in ELISA. Only ten (AP = 0.3%; TP = 0%) specimens proceeding from five farms (AP = 3.9%; TP = 1.7%) from Lombardy were confirmed positive to the WB, corresponding to two Holstein Friesian cows and eight beef cattle. IFAT showed a low sensitivity (44.4%) scoring positive in only four samples out of 9 positive to WB. Conclusions: The survey demonstrated that bovine besnoitiosis cannot still be considered endemic in whole Italy. In fact, independent foci of infection were registered only in Lombardy region. Therefore, a sanitary strategy aimed to increase control measures and to organize monitoring plans, by adequate diagnostic tools is necessary to avoid overestimation of B. besnoiti in Italy.</br

Translational Systems Biology of Inflammation

Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation. “Systems biology” is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians

Modeling Cell Gradient Sensing and Migration in Competing Chemoattractant Fields

Directed cell migration mediates physiological and pathological processes. In particular, immune cell trafficking in tissues is crucial for inducing immune responses and is coordinated by multiple environmental cues such as chemoattractant gradients. Although the chemotaxis mechanism has been extensively studied, how cells integrate multiple chemotactic signals for effective trafficking and positioning in tissues is not clearly defined. Results from previous neutrophil chemotaxis experiments and modeling studies suggested that ligand-induced homologous receptor desensitization may provide an important mechanism for cell migration in competing chemoattractant gradients. However, the previous mathematical model is oversimplified to cell gradient sensing in one-dimensional (1-D) environment. To better understand the receptor desensitization mechanism for chemotactic navigation, we further developed the model to test the role of homologous receptor desensitization in regulating both cell gradient sensing and migration in different configurations of chemoattractant fields in two-dimension (2-D). Our results show that cells expressing normal desensitizable receptors preferentially orient and migrate toward the distant gradient in the presence of a second local competing gradient, which are consistent with the experimentally observed preferential migration of cells toward the distant attractant source and confirm the requirement of receptor desensitization for such migratory behaviors. Furthermore, our results are in qualitative agreement with the experimentally observed cell migration patterns in different configurations of competing chemoattractant fields