High-risk corneal allografts : A therapeutic challenge

Peer reviewedPublisher PD

Cornea regeneration as an alternative to human donor transplantation

There is a need for an alternative to human donor corneas as the availability of good-quality tissues remains limited, with this situation potentially worsening as the population in many countries is progressively ageing. There have been numerous attempts to develop corneal equivalent as alternatives to donated human corneas as well as prostheses. In this short review, we focus on the efforts in bioengineering implants that promote regeneration by Canadian researchers, including our current team of authors. The examples of technologies developed that we describe include biomaterials that allow for partial regeneration of corneal tissue, self-assembled cornea constructs and cell-free corneal implants that promoted regeneration when evaluated in clinical trials in Europe

Tendencies of globalization of development of international tourism

Проаналізовано сучасні тенденції розвитку міжнародного туризму як провідного сегмента світового ринку, однієї із найважливіших складових процесу глобалізації. Визначено передумови глобалізації світового туристичного ринку, окреслено перспективи розвитку системи міжнародного туризму в сучасних умовах. Зміст міжнародного туризму як економічної категорії представлено як функціональну спрямованість його впливу на формування сучасної глобальної економічної системи, що проявляється в єдності його функцій.In the article modern progress of international tourism trends are analysed as a leading world market segment, one of major constituents of process of globalization. Pre-conditions of globalization of world tourist market are certain, the prospects of development of the system of international tourism are outlined in modern terms. The table of contents of international tourism as an economic category is presented as a functional orientation of his influence on forming of the modern global economic system that shows up in unity of his functions. Passing of international tourism to the global stage of the development was caused by the specific of the market state of affairs of the concrete historical stage, aspiring of large tourist companies to minimization of prime price of tourist package and increase of guarantees of grant of the announced tourist services of the proper quality; and also by the height of investment attractiveness of tourist business as a result of mass character of international tourism and increase of effect of scale in him. Global international tourism certainly as the socio-economic phenomenon that depends already not on domestic, but from external factors, maintenance and quantity of that determined by a global world concord the members of that are related to each other in all spheres of public life, including an economy, policy, ideology, culture, social sphere, ecology, safety. By the basic components of globalization of international tourism following: expansion of international economic connections in a tourist production, increase of internationalization of factors of tourist production, distribution of multinationals corporations in tourist business

A finite strain nonlinear human mitral valve model with fluid structure interaction

A simulated human mitral valve under a physiological pressure loading is developed using a hybrid finite element immersed boundary method, which incorporates experimentally based constitutive laws in a three-dimensional fluid-structure interaction framework. A transversely isotropic material constitutive model is used for characterizing the mechanical behaviour of the mitral valve tissue based on recent mechanical tests of healthy human mitral leaflets. Our results show good agreement, in terms of the flow rate and the closing and opening configurations, with the measurements from the magnetic resonance images. The stresses in the anterior leaflet are found to be higher than those in the posterior leaflet, and concentrated around the annulus trigons and free edges of the valve leaflets. Those areas are located where the leaflet has the highest curvature. Effects of the chordae tendineae in the material model are studied and the results show that these chordae play an important role in providing a secondary orifice for the flow when valve opens. Although there are some discrepancies to be overcome in future works, our simulations show that the developed computational model is promising in mimicking the in vivo mitral valve dynamics and providing important information that are not obtainable by in vivo measurements. This article is protected by copyright. All rights reserved

The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation.

Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost importance to develop integrative biomaterials based on multifunctional biopolymers and nanosystem for their practical and successful clinical translation

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

The spiral structure of our Milky Way Galaxy

The spiral structure of our Milky Way Galaxy is not yet known. HII regions and giant molecular clouds are the most prominent spiral tracers. We collected the spiral tracer data of our Milky Way from the literature, namely, HII regions and giant molecular clouds (GMCs). With weighting factors based on the excitation parameters of HII regions or the masses of GMCs, we fitted the distribution of these tracers with models of two, three, four spiral-arms or polynomial spiral arms. The distances of tracers, if not available from stellar or direct measurements, were estimated kinetically from the standard rotation curve of Brand & Blitz (1993) with $R_0$=8.5 kpc, and $\Theta_0$=220 km s$^{-1}$ or the newly fitted rotation curves with $R_0$=8.0 kpc and $\Theta_0$=220 km s$^{-1}$ or $R_0$=8.4 kpc and $\Theta_0$=254 km s$^{-1}$. We found that the two-arm logarithmic model cannot fit the data in many regions. The three- and the four-arm logarithmic models are able to connect most tracers. However, at least two observed tangential directions cannot be matched by the three- or four-arm model. We composed a polynomial spiral arm model, which can not only fit the tracer distribution but also match observed tangential directions. Using new rotation curves with $R_0$=8.0 kpc and $\Theta_0$=220 km s$^{-1}$ and $R_0$=8.4 kpc and $\Theta_0$=254 km s$^{-1}$ for the estimation of kinematic distances, we found that the distribution of HII regions and GMCs can fit the models well, although the results do not change significantly compared to the parameters with the standard $R_0$ and $\Theta_0$.Comment: 34 Pages, 10 Figures, 5 Tables. Accepted for publication in A&A. Edited

Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide

Aims Our objective was to investigate whether pro-oxidant properties of ascorbic acid (AA) and tetrahydrobiopterin (BH4) modulate endothelium-dependent, electrotonically mediated arterial relaxation. Methods and results In studies with rabbit iliac artery (RIA) rings, NO-independent, endotheliumderived hyperpolarizing factor (EDHF)-type relaxations evoked by the sarcoplasmic endoplasmic reticulum Ca2þ-ATPase inhibitor cyclopiazonic acid and the G protein-coupled agonist acetylcholine (ACh) were enhanced by AA (1 mM) and BH4 (200 mM), which generated buffer concentrations of H2O2 in the range of 40–80 mM. Exogenous H2O2 potentiated cyclopiazonic acid (CPA)- and ACh-evoked relaxations with a threshold of 10–30 mM, and potentiation by AA and BH4 was abolished by catalase, which destroyed H2O2 generated by oxidation of these agents in the organ chamber. Adventitial application of H2O2 also enhanced EDHF-type dilator responses evoked by CPA and ACh in RIA segments perfused intraluminally with H2O2-free buffer, albeit with reduced efficacy. In RIA rings, both control relaxations and their potentiation by H2O2 were overcome by blockade of gap junctions by connexinmimetic peptides (YDKSFPISHVR and SRPTEK) targeted to the first and second extracellular loops of the dominant vascular connexins expressed in the RIA. Superoxide dismutase attenuated the potentiation of EDHF-type relaxations by BH4, but not AA, consistent with findings demonstrating a differential role for superoxide anions in the generation of H2O2 by the two agents. Conclusion Pro-oxidant effects of AA and BH4 can enhance the EDHF phenomenon by generating H2O2, which has previously been shown to amplify electrotonic hyperpolarization-mediated relaxation by facilitating Ca2þ release from endothelial stores

Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation

The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal regeneration and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients