"Human skin represents an important endpoint to access the efficacy and toxicity of cosmetics and pharmaceuticals. In the last few years, there has been an increasing demand for the development and production of in vitro skin models for basic and applied research which led to important advancements in the field of skin tissue engineering. However, current in vitro skin models still do not recapitulate the complex architecture and physiology of the in vivo human skin. The main limitations of the models produced with conventional methods are the use of exogenous animal-derived hydrogels, high contractability, lack of physiologically relevant mechanical forces and perfusion. This results in low mechanical stability and in a significantly weaker skin barrier compared to the native skin. Consequently, there remains a dependence on animal models during preclinical drug trials which results in expensive drug development, high failure rates and ethical issues. (...)"

A navegação de nano/microdispositivos apresenta um grande potencial para aplicações biomédicas, oferecendo meios de diagnóstico e procedimentos terapêuticos no interior do corpo humano. Dada a sua capacidade de penetrar quase todos os materiais, os campos magnéticos são naturalmente adequados para controlar nano/microdispositivos magnéticos em espaços inacessíveis. Uma abordagem recente é o uso de um aparelho personalizado, capaz de controlar campos magnéticos. Esta é uma área de pesquisa prometedora, mas mais simulações e experiências são necessárias para avaliar a viabilidade destes sistemas em aplicações clínicas. O objectivo deste projecto foi a simulação e desenho de um sistema de atuação eletromagnética para estudar a locomoção bidimensional de microdispositivos. O primeiro passo foi identificar, através da análise de elementos finitos, usando o software COMSOL, diferentes configurações de bobines que permitiriam o controlo de dispositivos magnéticos em diferentes escalas. Baseado nos resultados das simulações, um protótipo de um sistema de atuação magnética para controlar dispositivos com mais de 100 m foi desenhado e construído de raiz, tendo em conta restrições de custos. O sistema consistiu num par de bobines de Helmholtz e rotacionais e um par de bobines de Maxwell dispostas no mesmo eixo. Além disso, componentes adicionais tiveram de ser desenhados ou selecionados para preencher os requisitos do sistema. Para a avaliação do sistema fabricado, testes preliminares foram realizados. A locomoção do microrobot foi testada em diferentes direções no plano x-y. As simulações e experiências confirmaram que é possível controlar a força magnética e o momento da força que atuam num microdispositivo através do campos produzidos pelas bobines de Maxwell e Helmholtz, respectivamente. Assim, este tipo de atuação magnética parece ser uma forma adequada de transferência de energia para futuros microdispositivos biomédicos.

The skin acts as a barrier to environmental insults and provides many vital functions. One of these is to shield DNA from harmful UV radiation, which is achieved by skin pigmentation arising as melanin is produced and dispersed within the epidermal layer. This is a crucial defence against DNA damage, photo-ageing and skin cancer. The mechanisms and regulation of melanogenesis and melanin transfer involve extensive crosstalk between melanocytes and keratinocytes in the epidermis, as well as fibroblasts in the dermal layer. Although the predominant mechanism of melanin transfer continues to be debated and several plausible models have been proposed, we and others previously provided evidence for a coupled exo/phagocytosis model. Herein, we performed histology and immunohistochemistry analyses and demonstrated that a newly developed full-thickness 3D reconstructed human pigmented skin model and an epidermis-only model exhibit dispersed pigment throughout keratinocytes in the epidermis. Transmission electron microscopy revealed melanocores between melanocytes and keratinocytes, suggesting that melanin is transferred through coupled exocytosis/phagocytosis of the melanosome core, or melanocore, similar to our previous observations in human skin biopsies. We therefore present evidence that our in vitro models of pigmented human skin show epidermal pigmentation comparable to human skin. These findings have a high value for studies of skin pigmentation mechanisms and pigmentary disorders, whilst reducing the reliance on animal models and human skin biopsies.

Poly(hydroxyalkanoates) (PHAs) with differing material properties, namely, the homo-polymer poly(3-hydroxybutyrate), P(3HB), the copolymer poly(3-hydroxybutyrate-co-3-hy-droxyvalerate), P(3HB-co-3HV), with a 3HV content of 25 wt.% and a medium chain length PHA, and mcl-PHA, mainly composed of 3-hydroxydecanoate, were studied as scaffolding material for cell culture. P(3HB) and P(3HB-co-3HV) were individually spun into fibers, as well as blends of the mcl-PHA with each of the scl-PHAs. An overall biopolymer concentration of 4 wt.% was used to prepare the electrospinning solutions, using chloroform as the solvent. A stable electrospinning process and good quality fibers were obtained for a solution flow rate of 0.5 mL h−1, a needle tip collector distance of 20 cm and a voltage of 12 kV for P(3HB) and P(3HB-co-3HV) solutions, while for the mcl-PHA the distance was increased to 25 cm and the voltage to 15 kV. The scaffolds’ hy-drophilicity was significantly increased under exposure to oxygen plasma as a surface treatment. Complete wetting was obtained for the oxygen plasma treated scaffolds and the water uptake degree increased in all treated scaffolds. The biopolymers crystallinity was not affected by the electro-spinning process, while their treatment with oxygen plasma decreased their crystalline fraction. Human dermal fibroblasts were able to adhere and proliferate within the electrospun PHA-based scaffolds. The P(3HB-co-3HV): mcl-PHA oxygen plasma treated scaffold highlighted the most promising results with a cell adhesion rate of 40 ± 8%, compared to 14 ± 4% for the commercial oxygen plasma treated polystyrene scaffold Alvetex™. Scaffolds based on P(3HB-co-3HV): mcl-PHA blends produced by electrospinning and submitted to oxygen plasma exposure are therefore promising biomaterials for the development of scaffolds for tissue engineering.