Strategic Project - UI 4056 - 2011-2012

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Publications

Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

Publication . Ribeiro, MP.; Morgado, Patrícia I.; Miguel, Sónia P.; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim Sobreira

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.

2013-03-24Journal article

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Effects of Body Fat and Dominant Somatotype on Explosive Strength and Aerobic Capacity Trainability in Prepubescent Children

Publication . Marta, Carlos C.; Marinho, Daniel; Barbosa, Tiago M.; Carneiro, André; Izquierdo, Mikel; Marques, Mário C.

The purpose of this study was to analyze the influence of body fat and somatotype on explosive strength and aerobic capacity trainability in the prepubertal growth spurt, marked by rapid changes in body size, shape, and composition, all of which are sexually dimorphic. One hundred twenty-five healthy children (58 boys, 67 girls), aged 10-11 years (10.8 ± 0.4 years), who were self-assessed in Tanner stages 1-2, were randomly assigned into 2 experimental groups to train twice a week for 8 weeks: strength training group (19 boys, 22 girls), endurance training group (21 boys, 24 girls), and a control group (18 boys, 21 girls). Evaluation of body fat was carried out using the method described by Slaughter. Somatotype was computed according to the Heath-Carter method. Increased endomorphy reduced the likelihood of vertical jump height improvement (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.01-0.85), increased mesomorphy (OR, 6.15; 95% CI, 1.52-24.88) and ectomorphy (OR, 6.52; 95% CI, 1.71-24.91) increased the likelihood of sprint performance, and increased ectomorphy (OR, 3.84; 95% CI, 1.20-12.27) increased the likelihood of aerobic fitness gains. Sex did not affect the training-induced changes in strength or aerobic fitness. These data suggest that somatotype has an effect on explosive strength and aerobic capacity trainability, which should not be disregarded. The effect of adiposity on explosive strength, musculoskeletal magnitude on running speed, and relative linearity on running speed and aerobic capacity seem to be crucial factors related to training-induced gains in prepubescent boys and girls.

2013Journal article

Open access

Thermoresponsive chitosan–agarose hydrogel for skin regeneration

Publication . Miguel, Sónia P.; Ribeiro, MP.; Brancal, Hugo Gonçalo Monteiro Silva Aguiar; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim Sobreira

Healing enhancement and pain control are critical issues on wound management. So far, different wound dressings have been developed. Among them, hydrogels are the most applied. Herein, a thermoresponsive hydrogel was produced using chitosan (deacetylation degree 95%) and agarose. Hydrogel bactericidal activity, biocompatibility, morphology, porosity and wettability were characterized by confocal microscopy, MTS assay and SEM. The performance of the hydrogel in the wound healing process was evaluated through in vivo assays, during 21 days. The attained results revealed that hydrogel has a pore size (90–400 μm) compatible with cellular internalization and proliferation. A bactericidal activity was observed for hydrogels containing more than 188 μg/mL of chitosan. The improved healing and the lack of a reactive or a granulomatous inflammatory reaction in skin lesions treated with hydrogel demonstrate its suitability to be used in a near future as a wound dressing.

2014-05-02Journal article

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In Vivo High-Content Evaluation of Three-Dimensional Scaffolds Biocompatibility

Publication . Oliveira, Mariana; Ribeiro, MP.; Miguel, Sónia; Neto, Ana; Coutinho, Paula Isabel Teixeira Gonçalves; Correia, Ilídio Joaquim Sobreira; Mano, João F.

While developing tissue engineering strategies, inflammatory response caused by biomaterials is an unavoidable aspect to be taken into consideration, as it may be an early limiting step of tissue regeneration approaches. We demonstrate the application of flat and flexible films exhibiting patterned high-contrast wettability regions as implantable platforms for the high-content in vivo study of inflammatory response caused by biomaterials. Screening biomaterials by using high-throughput platforms is a powerful method to detect hit spots with promising properties and to exclude uninteresting conditions for targeted applications. High-content analysis of biomaterials has been mostly restricted to in vitro tests where crucial information is lost, as in vivo environment is highly complex. Conventional biomaterials implantation requires the use of high numbers of animals, leading to ethical questions and costly experimentation. Inflammatory response of biomaterials has also been highly neglected in high-throughput studies. We designed an array of 36 combinations of biomaterials based on an initial library of four polysaccharides. Biomaterials were dispensed onto biomimetic superhydrophobic platforms with wettable regions and processed as freeze-dried three-dimensional scaffolds with a high control of the array configuration. These chips were afterward implanted subcutaneously in Wistar rats. Lymphocyte recruitment and activated macrophages were studied on-chip, by performing immunocytochemistry in the miniaturized biomaterials after 24 h and 7 days of implantation. Histological cuts of the surrounding tissue of the implants were also analyzed. Localized and independent inflammatory responses were detected. The integration of these data with control data proved that these chips are robust platforms for the rapid screening of early-stage in vivo biomaterials' response.

2014-02-25Journal article

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Evaluation of Nanoparticle Uptake in Co-culture Cancer Models

Publication . Costa, Elisabete C.; Gaspar, Vítor Manuel Abreu; Marques, João Filipe Gonçalves; Coutinho, Paula; Correia, Ilídio Joaquim Sobreira

Co-culture models are currently bridging the gap between classical cultures and in vivo animal models. Exploring this novel approach unlocks the possibility to mimic the tumor microenvironment in vitro, through the establishment of cancer-stroma synergistic interactions. Notably, these organotypic models offer a perfect platform for the development and pre-clinical evaluation of candidate nanocarriers loaded with anti-tumoral drugs in a high throughput screening mode, with lower costs and absence of ethical issues. However, this evaluation was until now limited to co-culture systems established with precise cell ratios, not addressing the natural cell heterogeneity commonly found in different tumors. Therefore, herein the multifunctional nanocarriers efficiency was characterized in various fibroblast-MCF-7 co-culture systems containing different cell ratios, in order to unravel key design parameters that influence nanocarrier performance and the therapeutic outcome. The successful establishment of the co-culture models was confirmed by the tissue-like distribution of the different cells in culture. Nanoparticles incubation in the various co-culture systems reveals that these nanocarriers possess targeting specificity for cancer cells, indicating their suitability for being used in this illness therapy. Additionally, by using different co-culture ratios, different nanoparticle uptake profiles were obtained. These findings are of crucial importance for the future design and optimization of new drug delivery systems, since their real targeting capacity must be addressed in heterogenous cell populations, such as those found in tumors.

2013-07-26Journal article

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