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A engenharia de tecidos utiliza células e biomateriais para desenvolver substitutos de tecidos bioartificiais com diferentes finalidades. Embora vários modelos de pele tenham sido desenvolvidos para estudos farmacêuticos e cosméticos, assim como para cicatrização de feridas cutâneas, existem poucos estudos sobre culturas 3D de queratinócitos em scaffolds impressos em 3D. Assim, o objetivo deste trabalho foi desenvolver um scaffold de hidrogel impresso em 3D capaz de promover o crescimento de queratinócitos humanos. Scaffolds 3D em forma de rede foram impressos, usando um método de extrusão, com um hidrogel de 20% de gelatina / 5% de alginato onde células HaCaT foram cultivadas durante 7 dias. Os scaffolds mantiveram a sua estrutura durante uma semana e a sua rigidez só diminuiu após 7 dias, demonstrando boas características mecânicas e estruturais, além de boa biodegradabilidade (27% de perda de peso). Queratinócitos viáveis (ensaio MTT) agregaram em forma de esferóides, que é um modelo 3D capaz de mimetizar as propriedades e fenótipos das células in vivo. Foram formados esferóides em 47% dos poros dos scaffolds e aumentaram de tamanho ao longo do tempo, mostrando uma proliferação celular promissora. A marcação de F-actina mostrou células com formas irregulares e interligadas e a sua organização ao longo do tempo. Este método oferece uma solução fácil e barata para a formação de esferóides de queratinócitos, que pode ser útil para engenharia de tecidos como um sistema de entrega de células, para pesquisa farmacológica ou básica ou aplicações médicas de cicatrização de feridas. / Tissue engineering uses cells and biomaterials to develop bioartificial tissue substitutes for different purposes. Although several skin models have been developed for pharmaceutical and cosmetic research, but also for skin wound healing, there are few studies on 3D cultures of keratinocytes in 3D printed scaffolds. So, the aim of this work was to develop a 3D-printed hydrogel scaffold able to promote human keratinocytes growth. Mesh 3D scaffolds were printed using an extrusion-based method with a 20% gelatin/ 5% alginate hydrogel where HaCaT cells were cultured for 7 days. Scaffolds kept their structure over one week and their stiffness only decreased after 7 days, showing good mechanical and structural characteristics, along with good biodegradability (27% weight lost). Viable keratinocytes (MTT assay) aggregated into spheroids, which is a 3D model capable of mimicking in vivo cells properties and phenotypes. Spheroids were formed on 47% of scaffolds pores and got larger over time, showing promising cell proliferation. F-actin staining showed cells irregular and interconnected shapes and organization over time. This method offers an easy and inexpensive solution for keratinocyte spheroid formation, which may be useful for tissue engineering as a cell delivery system, for pharmacological or basic research, or wound healing medical applications.

O tratamento de fraturas ósseas requer muitas vezes a utilização de implantes de fixação, que por vezes precisam de ser removidos cirurgicamente. Tais implantes e procedimentos aumentam a propensão dos doentes para desenvolver infeções associadas aos dispositivos médicos, sendo a osteomielite decorrente do trauma uma complicação desafiante para os ortopedistas. Nos últimos anos, os materiais biodegradáveis têm conquistado grande importância no desenvolvimento de dispositivos médicos temporários, evitando cirurgias de remoção. O objetivo desta revisão sistemática foi analisar a literatura sobre a utilização de implantes ósseos biodegradáveis na consolidação de fraturas e seu impacto na redução de infeções associadas a implantes. A revisão sistemática seguiu as diretrizes do PRISMA e baseou-se na pesquisa e análise de estudos publicados sobre o uso in vivo de implantes de fixação óssea biodegradável e sua atividade antibacteriana. De um total de 667 referências, 23 estudos foram incluídos com base nos critérios de inclusão e exclusão. Implantes ortopédicos biodegradáveis de Mg-Cu, Mg-Zn e Zn-Ag revelaram atividade antibacteriana, especialmente na redução da taxa de infeção por estirpes de MRSA, em modelos de osteomielite in vivo. A capacidade de certos dispositivos em prevenir e combater as infeções associadas a implantes, bem como a potencialidade para se degradarem gradualmente dentro do corpo reduzem a necessidade de uma segunda cirurgia de remoção do implante, com ganhos esperados no que diz respeito ao conforto dos doentes. Mais estudos in vivo serão necessários para avaliar a eficácia desses materiais biodegradáveis com propriedades antibacterianas. / Bone fractures often require fixation devices that frequently need to be surgically removed. These implants and procedures turn the patient more prone to develop medical device-associated infections, and osteomyelitis associated with trauma is a challenging complication for orthopedists. In recent years, biodegradable materials have gained great importance as temporary medical implant devices, avoiding removal surgery. The purpose of this systematic review was to revise the literature regarding the use of biodegradable bone implants in fracture healing and its impact on the reduction of implant-associated infections. The systematic review followed the PRISMA guidelines and was conducted by searching published studies regarding the in vivo use of biodegradable bone fixation implants and their antibacterial activity. From a total of 667 references, 23 studies were included based on inclusion and exclusion criteria. Biodegradable orthopedic implants of Mg-Cu, Mg-Zn, and Zn-Ag have shown antibacterial activity especially in reducing infection burden by MRSA strains in vivo osteomyelitis models. Their ability to prevent and tackle implant-associated infections and to gradually degrade inside the body reduces the need for a second surgery for implant removal, with expectable gains regarding patients' comfort. Further in vivo studies are mandatory to evaluate the efficiency of these antibacterial biodegradable materials.

Aim: Design nanostructured lipid carriers (NLC) to facilitate drug delivery to tuberculosis-infected areas, exploiting macrophage mannose receptors and assess their uptake in a 3D human lung model. Materials & methods: NLCs and mannosylated-NLCs were synthetized and characterized. Their uptake and biocompatibility were tested in a 3D human lung model. Results: The formulations have appropriate size (170-202 nm) and morphology for lung deposition. Cell membrane integrity was maintained and no significant pro-inflammatory cytokine (IL-1β, IL-8 and TNF-α) secretion or morphological changes were observed 24 h post nanoparticles exposure. NLCs and mannosylated NLCs were distributed in the apical side of the lung tissue, both in macrophages and in epithelial cells. Conclusion: NLCs are biocompatible carriers and can be used for pulmonary drug delivery. / Aim: Design nanostructured lipid carriers (NLC) to facilitate drug delivery to tuberculosis-infected areas, exploiting macrophage mannose receptors and assess their uptake in a 3D human lung model. Materials & methods: NLCs and mannosylated-NLCs were synthetized and characterized. Their uptake and biocompatibility were tested in a 3D human lung model. Results: The formulations have appropriate size (170-202 nm) and morphology for lung deposition. Cell membrane integrity was maintained and no significant pro-inflammatory cytokine (IL-1β, IL-8 and TNF-α) secretion or morphological changes were observed 24 h post nanoparticles exposure. NLCs and mannosylated NLCs were distributed in the apical side of the lung tissue, both in macrophages and in epithelial cells. Conclusion: NLCs are biocompatible carriers and can be used for pulmonary drug delivery.

This dissertation is framed in the scope of the European Project SelSus, which aims to develop a new life cycle based and distributed upon probabilistic diagnostic and predictive maintenance environment for repairing and renovation activities. To promote all the previously addressed issues, the innovative concept of Sensor Cloud is presented. This concept is intimately related with the development of both Wireless Sensor Networks (WSN) and Service-Oriented Architectures (SOA), along with capabilities for processing, reduction and generation of sensor data. As a point of interest and ease of implement of this Sensor Cloud, the Smart Node concept is explored as intermediate between sensors, considered lower capacity devices, and components that may require certain services from the Cloud. The application scenario is the automotive industry. The main purpose of this dissertation is the study how this Smart Node's concept can be extended in order to include humans in the sensing process, both for accessing their conditions (Body Wearable Sensors) and to use the human as an active sensor (Sensor Probe), promoting the integration of a diverse type of sensors (like ECG, EMG, ACC, Vision, etc) and software algorithms that will be embedded within this platform to facilitate collaboration and decision making on a distributed peer-to-peer basis. This new node will use BITALINO (http://bitalino.com/) as main implementation platform.

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Sulforafan är en isotiacyanat som beskrivs ha effektiva cancerpreventativa egenskaper. Kemikalien görs tillgänglig för människan genom konsumtion av korsblommiga grönsaker så som broccoli och grönkål. Cancer är vanligt, och i Sverige räknar man med att var tredje människa kommer att drabbas under sin livstid. I följande litteraturstudie var syftet att sammanställa information om på vilket sätt sulforafan påverkar koloncancerceller, samt söka evidens för att konsumtion av sulforafanrika grönsaker bidrar till minskad risk att drabbas av koloncancer. Sulforafan har cancerpreventativa egenskaper i cellkultur så som inhibering av histondeacetylas-aktivitet, inducering av cellcykelarrest och apoptos och minskad proliferation hos cancercellerna. Det minskar även uttryck av gener som är inblandade i angiogenes.Det finns inte nog med evidens om broccolikonsumtion, på grund av sitt höga innehåll av sulforafan, skulle vara cancerpreventativt hos människan. / Sulforaphane is an isothiocyanate that is described as having chemopreventative effects. The phytochemical is made available to humans by dietary consumption of cruciferous vegetables such as broccoli and kale. Cancer is a common disease, and in Sweden it is estimated that one in three will be diagnosed with cancer during their lifetime. This review study aims to summarize the effect of sulforaphane on human colon cancer cells, and seek evidence that consumption of cruciferous vegetables reduces the risk of developing colon cancer. Sulforaphane is considered chemopreventative in vitro through inhibition of histone deacetylas activity, induction of cell cycle arrest and apoptosis and through reduction of cell proliferation. It has also been shown to reduces expression of genes involved in angiogenesis.There is not enough evidence to confirm that dietary broccoli consumption, through its high content of sulforaphane, would be chemopreventative.