Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy

Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering

Fabrication of a Double-Cross-Linked Interpenetrating Polymeric Network (IPN) Hydrogel Surface Modified with Polydopamine to Modulate the Osteogenic Differentiation of Adipose-Derived Stem Cells

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials and Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acsami.8b05200.Hydrogel surface properties can be modified to form bioactive interfaces to modulate the osteogenic differentiation of stem cells. In this work, a hydrogel made of gelatin methacrylamide (GelMA) and alginate was designed and tested as a scaffold to control stem-cell osteogenic differentiation. The hydrogel’s surface was treated with polydopamine (pDA) to create an adhesive layer for the adsorption of the osteoinductive drug dexamethasone (Dex). The presence of the pDA coating enhanced Dex adsorption and retention over 21 days. This effect resulted in a delay in the osteogenic differentiation of hASCs cultured on the hydrogel treated with a pDA layer

Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis

Introduction Stem cell-based therapies represent a valid approach to restore cardiac function due to their beneficial effect in reducing scar area formation and promoting angiogenesis. However, their translation into the clinic is limited by the poor differentiation and inability to secrete sufficient therapeutic factors. To address this issue, several strategies such as genetic modification and biophysical pre-conditioning have been used to enhance the efficacy of stem cells for cardiac tissue repair. Methods In this study, a biomimetic approach was used to mimic the natural mechanical stimulation of the myocardium tissue. Specifically, human adipose-derived stem cells (hASCs) were cultured on a thin gelatin methacrylamide (GelMA) hydrogel disc and placed on top of a beating cardiomyocyte layer. qPCR studies and metatranscriptomic analysis of hASCs gene expression were investigated to confirm the correlation between mechanical stimuli and cardiomyogenic differentiation. In vivo intramyocardial delivery of pre-conditioned hASCs was carried out to evaluate their efficacy to restore cardiac function in mice hearts post-myocardial infarction. Results The cyclic strain generated by cardiomyocytes significantly upregulated the expression of both mechanotransduction and cardiomyogenic genes in hASCs as compared to the static control group. The inherent angiogenic secretion profile of hASCs was not hindered by the mechanical stimulation provided by the designed biomimetic system. Finally, in vivo analysis confirmed the regenerative potential of the pre-conditioned hASCs by displaying a significant improvement in cardiac function and enhanced angiogenesis in the peri-infarct region. Conclusion Overall, these findings indicate that cyclic strain provided by the designed biomimetic system is an essential stimulant for hASCs cardiomyogenic differentiation, and therefore can be a potential solution to improve stem-cell based efficacy for cardiovascular repair

Investigation of human adipose-derived stem-cell behavior using a cell-instructive polydopamine-coated gelatin-alginate hydrogel.

Hydrogels can be fabricated and designed to exert direct control over stem cells\u27 adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)-treatment as a binding platform for bioactive compounds to create a versatile gelatin-alginate (Gel-Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose-derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro-angiogenic peptide (QK). The pDA treatment efficiently retained the drug and the peptide compared to the untreated hydrogel and proved to be effective in controlling the morphology, cell area, and osteogenic differentiation of hASCs. Overall, the findings of this study confirm the efficacy of pDA treatment as a valuable strategy to modulate the biological properties of biocompatible Gel-Alg hydrogels and further extend their value in regenerative medicine

LPS-responsive beige-like anchor gene mutation associated with possible bronchiolitis obliterans organizing pneumonia associated with hypogammaglobulinemia and normal IgM phenotype and low number of B

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs * 2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency. © 2016 Tehran University of Medical Sciences. All rights reserved

The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children

<p>Abstract</p> <p>Background</p> <p>This study aimed to assess the relationship of air pollution and plasma surrogate markers of endothelial dysfunction in the pediatric age group.</p> <p>Methods</p> <p>This cross-sectional study was conducted in 2009-2010 among 125 participants aged 10-18 years. They were randomly selected from different areas of Isfahan city, the second large and air-polluted city in Iran. The association of air pollutants' levels with serum thrombomodulin (TM) and tissue factor (TF) was determined after adjustment for age, gender, anthropometric measures, dietary and physical activity habits.</p> <p>Results</p> <p>Data of 118 participants was complete and was analyzed. The mean age was 12.79 (2.35) years. The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 μm (PM₁₀) was more than twice the normal level. Multiple linear regression analysis showed that TF had significant relationship with all air pollutants except than carbon monoxide, and TM had significant inverse relationship with ozone. The odds ratio of elevated TF was significantly higher in the upper vs. the lowest quartiles of PM₁₀, ozone and PSI. The corresponding figures were in opposite direction for TM.</p> <p>Conclusions</p> <p>The relationship of air pollutants with endothelial dysfunction and pro-coagulant state can be an important factor in the development of atherosclerosis from early life. This finding should be confirmed in future longitudinal studies. Concerns about the harmful effects of air pollution on children's health should be considered a top priority for public health policy; it should be underscored in primordial and primary prevention of chronic diseases.</p

Low carbon technology performance vs infrastructure vulnerability: Analysis through the local and global properties space

Renewable energy technologies, necessary for low-carbon infrastructure networks, are being adopted to help reduce fossil fuel dependence and meet carbon mitigation targets. The evolution of these technologies has progressed based on the enhancement of technology-specific performance criteria, without explicitly considering the wider system (global) impacts. This paper presents a methodology for simultaneously assessing local (technology) and global (infrastructure) performance, allowing key technological interventions to be evaluated with respect to their effect on the vulnerability of wider infrastructure systems. We use exposure of low carbon infrastructure to critical material supply disruption (criticality) to demonstrate the methodology. A series of local performance changes are analyzed; and by extension of this approach, a method for assessing the combined criticality of multiple materials for one specific technology is proposed. Via a case study of wind turbines at both the material (magnets) and technology (turbine generators) levels, we demonstrate that analysis of a given intervention at different levels can lead to differing conclusions regarding the effect on vulnerability. Infrastructure design decisions should take a systemic approach; without these multilevel considerations, strategic goals aimed to help meet low-carbon targets, that is, through long-term infrastructure transitions, could be significantly jeopardized