Tamer Ahmed

Fibrin: A Versatile Scaffold for Tissue Engineering Applications

Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace damaged or diseased organs and tissues. Fibrin is a critical blood component responsible for hemostasis, which has been used extensively as a biopolymer scaffold in tissue engineering. In this review we summarize the latest developments in organ and tissue regeneration using fibrin as the scaffold material. Commercially available fibrinogen and thrombin are combined to form a fibrin hydrogel. The incorporation of bioactive peptides and growth factors via a heparin-binding delivery system improves the functionality of fibrin as a scaffold. New technologies such as inkjet printing and magnetically influenced self-assembly can alter the geometry of the fibrin structure into appropriate and predictable forms. Fibrin can be prepared from autologous plasma, and is available as glue or as engineered microbeads. Fibrin alone or in combination with other materials has been used as a biological scaffold for stem or primary cells to regenerate adipose tissue, bone, cardiac tissue, cartilage, liver, nervous tissue, ocular tissue, skin, tendons, and ligaments. Thus, fibrin is a versatile biopolymer, which shows a great potential in tissue regeneration and wound healing.

Mesenchymal stem cell-based tissue engineering strategies for repair of articular cartilage.

Restoration of articular cartilage function and structure following pathological or traumatic damage is still considered a challenging problem in the orthopaedic field. Currently, tissue engineering-based reconstruction of articular cartilage is a feasible and continuously developing strategy to restore structure and function. Successful articular cartilage tissue engineering strategy relies largely on several essential components including cellular component, supporting 3D carrier scaffolding matrix, bioactive agents, proper physical stimulants, and safe gene delivery. Designing the right formulations from these components remain the main concern of the orthopaedic community. Utilization of mesenchymal stem cells (MSCs) for articular cartilage tissue engineering is continuously increasing compared to use of chondrocytes. Various sources of MSCs have been investigated including adipose tissue, amniotic fluid, blood, bone marrow, dermis, embryonic stem cells, infrapatellar fat pad, muscle, periosteum, placenta, synovium, trabecular bone, and umbilical cord. MSCs derived from bone marrow and umbilical cord are currently in different phases of clinical trials. A wide range of matrices have been investigated to develop tissue engineering-based strategies including carbohydrate-based scaffolds (agarose, alginate, chitosan/chitin, and hyaluronate), protein-based scaffolds (collagen, fibrin, and gelatin), and artificial polymers (polyglycolic acid, polylactic acid, poly(lactic-co-glycolic acid), polyethylene glycol, and polycaprolactone). Collagen-based scaffolds and photopolymerizable PEG-based scaffolds are currently in different phases of clinical trials. TGF-β1, TGF-β3, BMP-2, and hypoxic environment are the recommended bioactive agents to induce optimum chondrogenesis of MSCs, while TGF-β1, TGF-β3, SOX-9, BMP-2, and BMP-7 genes are the best candidate for gene delivery to MSCs. Electromagnetic field and the combination of shear forces/dynamic compression are the best maturation-promoting physical stimulants.

Sources of social support associated with health and quality of life: a cross-sectional study among Canadian and Latin American older adults.

Objectives To examine whether the association between emotional support and indicators of health and quality of life differs between Canadian and Latin American older adults. Design Cross-sectional analysis of the International Mobility in Aging Study (IMIAS). Social support from friends, family members, children and partner was measured with a previously validated social network and support scale (IMIAS-SNSS). Low social support was defined as ranking in the lowest site-specific quartile. Prevalence ratios (PR) of good health, depression and good quality of life were estimated with Poisson regression models, adjusting for age, gender, education, income and disability in activities of daily living. Setting Kingston and Saint-Hyacinthe in Canada, Manizales in Colombia and Natal in Brazil. Participants 1600 community-dwelling adults aged 65–74u2005years, n=400 at each site. Outcome measures Likert scale question on self-rated health, Center for Epidemiological Studies Depression Scale and 10-point analogical quality-of-life (QoL) scale. Results Relationships between social support and study outcomes differed between Canadian and Latin American older adults. Among Canadians, those without a partner had a lower prevalence of good health (PR=0.90; 95% CI 0.82 to 0.98), and those with high support from friends had a higher prevalence of good health (PR=1.09; 95% CI 1.01 to 1.18). Among Latin Americans, depression was lower among those with high levels of support from family (PR=0.63; 95% CI 0.48 to 0.83), children (PR=0.60; 95% CI 0.45 to 0.80) and partner (PR=0.57; 95% CI 0.31 to 0.77); good QoL was associated with high levels of support from children (PR=1.54; 95% CI 1.20 to 1.99) and partner (PR=1.31; 95% CI 1.03 to 1.67). Conclusions Among older adults, different sources of support were relevant to health across societies. Support from friends and having a partner were related to good health in Canada, whereas in Latin America, support from family, children and partner were associated with less depression and better QoL.

In-depth comparative analysis of the chicken eggshell membrane proteome.

The avian eggshell membrane (ESM) is stabilized by extensive cross-linkages, making the identification of its protein constituents technically challenging. Herein, we applied various extraction/solubilization conditions followed by proteomic analysis to characterize the protein constituents of ESM derived from the unfertilized chicken eggs. The egg white and eggshell proteomes (including previous published work) were determined and compared to ESM to identify proteins that are relatively or highly specific to ESM. Merging the results from different extraction/solubilization conditions with various proteomes allowed the identification of 472, 225, and 488 proteins in the ESM, egg white, and eggshell proteomes, respectively. Of these, 163 and 124 proteins were relatively or highly specific to ESM, respectively. GO term analysis of the common proteins and ESM unique proteins generated 8 and 9 significantly enriched functional groups, respectively. Different families of proteins that were identified as ESM-specific included collagens, CREMPs, histones, AvBDs, lysyl oxidase-like 2 (LOXL2), and ovocalyxin-36 (OCX36). These proteins serve as a foundation for the mechanically stable ESM that rests upon the egg white compartment and is a physical barrier against pathogen invasion. Overall, our results highlight the structural nature of the ESM constituents that are relevant to various biomedical applications, such as wound healing.nnnBIOLOGICAL SIGNIFICANCEnThe eggshell membranes (ESM) are a highly resilient double-layered fibrous meshwork that is secreted while the forming egg transits a specialized oviduct segment, the white isthmus. The ESM protects against pathogen invasion and provides a platform for nucleation of the calcitic eggshell (ES). ESM is greatly stabilized by the extensive desmosine, isodesmosine and disulfide cross-linkages which make the identification of its protein constituents by standard proteomic approaches technically challenging. Comparative proteomic analyses of ESM, egg white, and ES proteins showed proteins groups that are relatively or highly specific to ESM. These groups of proteins serve as a foundation for the mechanically stable ESM that rests upon the egg white compartment and is a physical barrier against pathogen invasion. These features are essential for eggshell quality and for the prevention of pathogen invasion which reinforce food safety of the table egg.

Gender Roles and Physical Function in Older Adults: Cross-Sectional Analysis of the International Mobility in Aging Study (IMIAS).

Objectives To examine the relationships between physical function and gender-stereotyped traits and whether these relationships are modified by sex or social context. Methods A total of 1995 community-dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Tirana (Albania), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). We performed a cross-sectional analysis. Study outcomes were mobility disability, defined as having difficulty in walking 400 meters without assistance or climbing a flight of stairs without resting, and low physical performance, defined as a score < 8 on the Short Physical Performance Battery. The 12-item Bem Sex Role Inventory (BSRI) was used to classify participants into four gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using site-specific medians of femininity and masculinity as cut-off points. Poisson regression models were used to estimate prevalence rate ratios (PRR) of mobility disability and poor physical performance according to gender roles. Results In models adjusted for sex, marital status, education, income, and research site, when comparing to the androgynous role, we found higher prevalence of mobility disability and poor physical performance among participants endorsing the feminine role (PRR = 1.20, 95% confidence interval (CI) 1.03–1.39 and PRR = 1.37, CI 1.01–1.88, respectively) or the undifferentiated role (PRR = 1.23, 95% CI 1.07–1.42 and PRR = 1.58, CI 1.18–2.12, respectively). Participants classified as masculine did not differ from androgynous participants in prevalence rates of mobility disability or low physical performance. None of the multiplicative interactions by sex and research site were significant. Conclusion Feminine and undifferentiated gender roles are independent risk factors for mobility disability and low physical performance in older adults. Longitudinal research is needed to assess the mediation pathways through which gender-stereotyped traits influence functional limitations and to investigate the longitudinal nature of these relationships.

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study

PurposenActive aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada.nnnMethodsnThe WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario.nnnResultsnNeither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO.nnnImplicationsnOur results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults.

An adjoint-based approach to computing time-domain sensitivity of multiport systems described by reduced-order models

This paper describes a new algorithm for obtaining time-domain sensitivity information of large linear networks via projection-based model-order reduction (MOR) techniques. The proposed algorithm enables adjoint-based time-domain sensitivity analysis techniques to be applied to a large network containing multiple linear multiport subnetworks. In addition, the proposed algorithm can also be used to obtain frequency-domain sensitivity information. The efficiency and accuracy of the proposed work is demonstrated through optimizing the time-domain waveforms of a high-speed interconnect circuit with nonlinear terminations.

Depression, Sex and Gender Roles in Older Adult Populations: The International Mobility in Aging Study (IMIAS).

Objectives To assess the associations between gender roles and depression in older men and women and whether gender roles are independent risk factors for depression. Methods International cross-sectional study of adults between 65 and 74 years old (n = 1,967). Depression was defined by a score of 16 or over in the Center for Epidemiologic Studies Depression Scale (CES-D). A validated 12-item Bem Sex Role Inventory (BSRI) was used to classify participants in gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using research site medians of femininity and masculinity as cut-off points. Poisson regressions were fitted to estimate the prevalence ratios (PR) of depression for each gender role compared to the masculine role, adjusting for sex, sufficiency of income, education, marital status, self-rated health, and chronic conditions. Results Among men, 31.2% were androgynous, 26% were masculine, 14.4% were feminine, and 28.4% were undifferentiated; among women, the corresponding percentages were 32.7%, 14.9%, 27%, and 25.4%. Both in men and in women, depressive symptoms (CES-D≥16) were more prevalent in those endorsing the undifferentiated type, compared to masculine, feminine or androgynous groups. However, after adjusting for potential confounders, compared to the masculine group only those endorsing the androgynous role were 28% less likely to suffer from depression: PR of 0.72 (95% CI: 0.55–0.93). In fully adjusted models, prevalence rates of depression were not different from masculine participants in the two other gender groups of feminine and undifferentiated. Conclusions Androgynous roles were associated with lower rates of depression in older adults, independently of being a man or a woman.

Bem Sex Role Inventory Validation in the International Mobility in Aging Study

Cette étude, en utilisant différentes méthodes d’analyse des facteurs, a examiné la structure de mesure de l’Inventaire des rôles sexués de Bem (IRSB). La plupart des études antérieures sur la validité ont appliqué analyse factorielle exploratoire (AFE) d’examiner l’IRSB. Il s’agissait d’évaluer les propriétés psychométriques et la validité de la construction de la forme courte IRSB comprenant 12 articles dans un échantillon administré à 1,995 personnes âgées de la vague 1 de l’Initiative internationale de la mobilité en viellissement (IIMV). Nous avons utilisé l’alpha de Cronbach pour évaluer la fiabilité et la cohérence interne et une analyse factorielle confirmatoire (AFC) afin d’évaluer les propriétés psychometriques. AFE a révélé un modèle comprenant trois facteurs, qu’on a confirmé par l’AFC, puis ceci est comparé avec le modèle structurel initial de deux facteurs. Les résultats ont révélé qu’une solution à deux facteurs (instrumentalité-expression) a montré satisfaisante validité conceptuelle et un ajustement supérieur aux données, par rapport à la solution à trois facteurs. La solution à deux facteurs confirme différences attendues entre les sexes chez les personnes âgées. L’IRSB composé de 12 articles fournit un instrument bref, psychométrique et fiable dans les échantillons internationaux des personnes âgées. This study investigated the measurement structure of the Bem Sex Role Inventory (BSRI) with different factor analysis methods. Most previous studies on validity applied exploratory factor analysis (EFA) to examine the BSRI. We aimed to assess the psychometric properties and construct validity of the 12-item short-form BSRI in a sample administered to 1,995 older adults from wave 1 of the International Mobility in Aging Study (IMIAS). We used Cronbach’s alpha to assess internal consistency reliability and confirmatory factor analysis (CFA) to assess psychometric properties. EFA revealed a three-factor model, further confirmed by CFA and compared with the original two-factor structure model. Results revealed that a two-factor solution (instrumentality-expressiveness) has satisfactory construct validity and superior fit to data compared to the three-factor solution. The two-factor solution confirms expected gender differences in older adults. The 12-item BSRI provides a brief, psychometrically sound, and reliable instrument in international samples of older adults.

Fibrin for Encapsulation of Human Mesenchymal Stem Cells for Chondrogenic Differentiation

Age-related wear and tear of cartilage (osteoarthritis) and traumatic cartilage damage are a leading cause of disability in developed nations. Articular (hyaline) cartilage covers the ends of the bones of synovial joints and is a complex, multilayered structure varying in composition with location in a joint, and in relation to load and shear forces at that specific site. When damaged, articular cartilage tissue does not have the ability to repair itself, but rather is usually replaced by fibrocartilage which does not have suitable compressive properties, leading to breakdown, pain and can ultimately require replacement by prosthetic joint. Thus, cartilage repair remains a clinical challenge and few current treatments yield satisfactory clinical results over the long term. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function, and provides a scientific basis for integrating the proper cell populations, suitable cellular signals and appropriate scaffolds for optimum tissue development and organ replacement strategies. Fibrin has been used as both a delivery vehicle and as a scaffolding matrix for tissue engineering. The emergence of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine is due to their capability to repopulate and differentiate into several tissue lineages, including both cartilage and bone. Human MSCs have been used in combination with a wide range of fibrin scaffolds including both autologous and allogeneic human fibrin glue either as a platelet-rich or normal formulation, in addition to commercially available bovine fibrin hydrogel precursors. This approach permits high density of cells to be implanted, wherein chemical manipulation of the fibrin scaffold modulates its stability, strength and complement of growth factors, while maintaining the promise of an autologous repair solution. This review focuses on recent advances in the application of the fibrinogen/fibrin system for tissue engineering of articular cartilage.