Macrophages are key cells during inflammation and repair. Their activity is highly varied and requires precise regulation. The characterisation of cues coordinating macrophage functions has focussed on chemical and biological soluble mediators. Little is known about their responses to physical stimuli, in particular electric fields (EF) that are generated naturally in wounded tissue and infected tissue. Importantly, EFs are known to accelerate wound healing and limit infection but the mechanisms of this remain poorly understood. To address this gap in understanding, this study tested how key properties of human monocyte-derived macrophages are regulated by applied EFs equivalent to physiological EF strengths generated naturally. Using live-cell video microscopy, we show macrophage migration is directed anodally by EFs as low as 5 mV/mm and is EF-strength dependent, with effects peaking around 300 mV/mm. In contrast, monocytes, as macrophage-precursors, migrate in the opposite, cathodal direction. Strikingly, we show for the first time that EFs significantly enhance macrophage phagocytic uptake of a variety of targets, including carboxylate beads, apoptotic neutrophils and the nominal opportunist pathogen Candida albicans, all of which engage different classes of surface receptors. These EF-induced functional changes are accompanied by clustering of phagocytic receptors, enhanced PI3K and ERK activation, mobilization of intracellular calcium and actin polarization. EFs also selectively modulate cytokine production and augment effects of conventional polarising stimuli on cytokine secretion. Taken together, electrical signals have been identified as major contributors to the co-ordination and regulation of important human macrophage functions, including those essential for microbial clearance and healing. Our results open up a new area of research into effects of naturally occurring and clinically-applied EFs in conditions where macrophage activity is crucial.

No description available.

Thesis advisor: Thomas Stegman / Thesis advisor: Liam Bergin / Thesis (STL) — Boston College, 2014. / Submitted to: Boston College. School of Theology and Ministry. / Discipline: Sacred Theology.

A utilização do ultra som com a finalidade de acelerar o reparo tecidual é muito freqüente na prática clínica, embora as bases científicas para sua utilização não estejam bem estabelecidas. Este estudo analisou os efeitos do ultra som na cicatrização de tendões flexores de coelhos após tenorrafia. Foram utilizados 30 coelhos da raça Nova Zelândia, com peso médio de 2,7 Kg, divididos em dois grupos de 15 animais submetidos a tenotomia e tenorrafia com sutura tipo Kessler do tendão flexor profundo do terceiro dedo da pata dianteira direita. Após 24 horas foi iniciado em um dos grupos tratamento com ultra som, sendo o outro grupo utilizado para controle. A freqüência utilizada foi a de 3 MHz e a intensidade de 0,8 W/centímetro quadrado (SATA), por contato direto durante 7 dias consecutivos. Cada grupo foi dividido em subgrupos com 5 animais cada, e estes sacrificados em períodos distintos (8, 15 e 30 graus PO), e o tendão operado, dissecado e submetido à análise histológica pela microscopia de luz, analisando a reação inflamatória, grau de necrose, proliferação de fibroblastos, deposição de colágeno e formação de granuloma. Os resultados mostraram que o ultra som interferiu com o processo de reparo tecidual após a tenorrafia dos tendões flexores de coelhos / The use of ultrasound aiming to accelerate tissue healing is very frequent in clinical pratice, although the scientific basis to its use are not well established. This study analized the effects of ultrasound on the healing of rabbit’s flexor tendons after repair. It was used 30 New Zealand rabbits, with an average weight of 2.7 Kg, divided in two groups of 15 animal. They were submetted to tenotomy and repair with Kessler’s suture on deep flexor tendon of the middle right front claw. After 24 hour one of the groups started the ultrasound treatment, and the other was de control group. The ultrasound frequency used was 3 MHz and the intensity was 0.8 W/square cemtimeter (SATA), by direct contact during 7 consecutive days. Each group was divided in subgroups with 5 animals each, and these were killed in distincts periods (PO 8, 15 and 30), and the operated tendon was dissected and submitted to histologic analises by light microscopy, anlaysing the inflammatory reaction, necrosis degree, fibroblasts proliferation, colagen synthesis and granulom formation. The result showed that ultrasound interfere on the tissue healing process after repair on the rabbit’s flexor tendons

Epoxy coatings are currently the most popular corrosion protection mechanism for steel reinforcement in structural concrete. However, these coatings are easily damaged on worksites, negating their intended purpose. This study investigates self-healing coatings for steel reinforcement to introduce an autonomous healing mechanism for damaged coatings. Coatings were applied to steel coupons, intentionally damaged, and introduced to a corrosive environment via aerated salt-water tanks. Performance of the experimental coatings was evaluated qualitatively and quantitatively. Adhesion strength and effects of coating thickness were also studied. Results from coated steel coupons subjected to damage and submerged in salt-water aeration tanks exhibited improved corrosion resistance performance with self-healing coatings. However, self-healing coatings have comparable poor adhesion to the substrate as do conventional coatings. This paper shows preliminary results demonstrating the potential benefits of self-healing coatings for steel reinforcement and identifies numerous avenues for future research.

Orientador: Lucilene Delazari dos Santos / Coorientador: Luciana Patricia Fernandes Abbade / Resumo: Introdução: Úlceras venosas crônicas atingem até 4% da população mundial >65 anos, causando impacto socioeconômico, principalmente relacionado à diminuição da mobilidade e autoestima. O exsudato destas lesões, pode ser útil na identificação dos fatores envolvidos na reparação tecidual. Objetivos: Identificar proteínas expressas no exsudato de úlceras venosas, agrupando-as de acordo com suas principais funções, e correlancionando-as com variaveis clínicas e epidemiológicas. Métodos: Estudo clínico do tipo transversal, descritivo e analítico envolvendo trinta e sete úlceras de 28 pacientes. Todos os pacientes foram submetidos à questionário clínico-epidemiológico auto descritivo, análise de área e a coleta de exsudato das úlceras. Fluidos das lesões foram submetidos à digestão tríptica em solução e sequenciados por espectrometria de massas para identificação do perfil proteômico. A análise multivariada entre dados clínicos e expressão proteica do exsudato foi explorada por escalonamento multidimensional, a partir da distância euclidiana entre as variáveis. Resultados: A maioria dos pacientes era do sexo feminino (62%), com idade média de 70(±10.1) anos, relatando adesão à compressão e ao repouso, histórico de varizes primárias e hipertensão arterial sistêmica, apresentando tecido desvitalizado no leito da ferida e tempo de evolução >10 anos. Foram identificadas 74 proteínas no exsudato, agrupadas de acordo com sua principal função na cicatrização. O perfil proteômico evidenciou... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: not available / Mestre

Orientador: Rosemary Adriana Chiérici Marcantonio / Resumo: O objetivo desse estudo foi avaliar o efeito de uma membrana de látex natural sobre a cicatrização de feridas no palato duro provenientes da remoção de enxerto gengival livre. Vinte e quatro pacientes participaram desse estudo e foram divididos aleatoriamente em 2 grupos de acordo com o tratamento utilizado para proteger o leito doador: Grupo controle (GC): A ferida foi recoberta com placa acrílica associada ao cimento cirúrgico (n=14); Grupo Látex (GL): A ferida foi recoberta com placa acrílica associada a membrana de látex natural (n=10). Foram realizadas tomadas fotográficas padronizadas das regiões das feridas nos períodos de baseline, 3, 7, 15 e 30 dias após o procedimento cirúrgico. Um examinador cego e calibrado realizou avaliação clínica, levando se em consideração os parâmetros: 1) fechamento de ferida; 2) área de superfície epitelizada por meio da utilização da água oxigenada aplicada na região; 3) Avaliação do auto relato de sensação dolorosa por meio da aplicação da escala de dor VAS. Os resultados obtidos mostraram que em ambos os grupos, houve diminuição gradativa da área da ferida cirúrgica, sendo que a partir dos 15 dias essa era inexistente para todos os pacientes avaliados e em relação à dor houve uma redução significativa da sensibilidade dolorosa relatada pelos pacientes do grupo látex em relação ao grupo controle. O uso da membrana de látex não promoveu efeito adicional a cicatrização, apresentando os mesmos resultados clínicos que a utilização de cimento... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this project was to evaluate the effect of a natural latex membrane in wound healing on donor sites of free gingival grafts. Twenty-four patients were used in this study and were randomly divided in 2 groups according with the treatment used to protect the donor site: Control group (CG) – Donor site was covered with an acrylic plate associated with surgical cement (n=14); Látex group (LG) – Donor site was covered with acrylic plate associated with a natural latex membrane and surgical cement (n=10). At baseline, 3, 7, 15 and 30 days after surgery, standardized photos of the wound were taken. A blind and calibrated examiner made the clinical evaluation by considering the parameters: 1) total wound area; 2) epithelized surface area through the use of hydrogen peroxide applied in the region; 3) Evaluation of self-report of pain sensation through the application of the VAS pain scale. The achieve results showed that both groups had a gradual decrease in the area of the surgical wound, and from 15 days this was non-existent for all patients evaluated and on the pain avaliation we found that the patients in latex group had significant reduction in reported pain when compared to the control group. The use of natural latex membrane didn’t promote any additional effect for wound healing, showing the same clinical results as the use of surgical cement with the addition of a lower pain report by the patients. / Mestre

by Chong Wai Sing, Wilson. / Thesis submitted in: August 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 116-126). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.i / ABBREVIATION --- p.ii / ABSTRACT (Chinese & English) --- p.iii / TABLE OF CONTENT --- p.vii / INDEX FOR FIGURES --- p.x / INDEX FOR TABLES --- p.xiii / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- "Bone-tendon junction - types, structures and functions" --- p.2 / Chapter 1.1.1 --- Indirect insertion --- p.3 / Chapter 1.1.2 --- Direct insertion --- p.3 / Chapter 1.1.3 --- Functional adaptations of insertions --- p.4 / Chapter 1.2 --- Incidence and type of injuries near insertion site --- p.5 / Chapter 1.3 --- Treatment protocol for injuries near insertion site --- p.5 / Chapter 1.3.1 --- Non-operative versus operative approach --- p.5 / Chapter 1.3.2 --- Previous studies on validations of outcomes of difference repair methods --- p.6 / Chapter 1.4 --- Modes of healing underlying different repair approach --- p.7 / Chapter 1.4.1 --- Fracture healing --- p.7 / Chapter 1.4.2 --- Tendon healing --- p.8 / Chapter 1.4.3 --- Bone-tendon healing --- p.9 / Chapter 1.5 --- Objectives --- p.9 / Chapter 2. --- Materials and Methods --- p.12 / Chapter 2.1 --- Animal model --- p.13 / Chapter 2.2 --- Experimental design --- p.13 / Chapter 2.3 --- Surgery --- p.13 / Chapter 2.3.1 --- Bone-to-bone repair --- p.14 / Chapter 2.3.2 --- Bone-to-tendon repair --- p.14 / Chapter 2.3.3 --- Tendon-to-tendon repair --- p.15 / Chapter 2.4 --- Post-operative follow-up --- p.15 / Chapter 2.4.1 --- Radiographic examination --- p.15 / Chapter 2.4.2 --- Polychrome sequential labeling --- p.16 / Chapter 2.4.2.1 --- Reagents --- p.16 / Chapter 2.4.2.2 --- Route of administration --- p.16 / Chapter 2.5 --- Sampling --- p.17 / Chapter 2.6 --- Histology --- p.17 / Chapter 2.6.1 --- Decalcification --- p.17 / Chapter 2.6.1.1 --- Tissue decalcification --- p.17 / Chapter 2.6.1.2 --- Tissue processing --- p.17 / Chapter 2.6.1.3 --- Immunohistochemistry of collagen type II and III --- p.18 / Chapter 2.6.1.3.1 --- Reagents and solution preparation --- p.18 / Chapter 2.6.1.3.2 --- Experimental procedures --- p.20 / Chapter 2.6.2 --- Undecalcification --- p.22 / Chapter 2.6.2.1 --- Specimen preparations --- p.22 / Chapter 2.6.2.2 --- Toluidine blue staining --- p.22 / Chapter 2.7 --- Mechanical test --- p.23 / Chapter 2.7.1 --- Sample preparation --- p.23 / Chapter 2.7.2 --- Embedding procedures --- p.23 / Chapter 2.7.3 --- Measurement of cross-sectional area of healing interface --- p.23 / Chapter 2.7.3.1 --- CSA for BB --- p.23 / Chapter 2.7.3.2 --- CSA for BT and TT --- p.24 / Chapter 2.7.4 --- Tensile test --- p.24 / Chapter 2.7.4.1 --- Testing procedures --- p.24 / Chapter 2.7.4.2 --- Interpretation of testing results --- p.25 / Chapter 2.7.5 --- Statistical analysis --- p.26 / Chapter 3. --- Results --- p.42 / Chapter 3.1 --- Surgical outcome --- p.43 / Chapter 3.1.1 --- Radiographic examination --- p.43 / Chapter 3.1.1.1 --- Bone-to-bone healing --- p.43 / Chapter 3.1.1.2 --- Bone-to-tendon healing --- p.44 / Chapter 3.1.2 --- Fluorochrome injection --- p.44 / Chapter 3.2 --- Histology --- p.45 / Chapter 3.2.1 --- Bone-to-bone healing --- p.45 / Chapter 3.2.1.1 --- Gross anatomy --- p.45 / Chapter 3.2.1.2 --- Microscopic examination --- p.45 / Chapter 3.2.1.3 --- Polarised light microscopy --- p.46 / Chapter 3.2.1.4 --- Fluorochrome microscopy --- p.46 / Chapter 3.2.2 --- Bone-to-tendon healing --- p.47 / Chapter 3.2.2.1 --- Gross anatomy --- p.47 / Chapter 3.2.2.2 --- Microscopic examination --- p.47 / Chapter 3.2.2.3 --- Polarised light microscopy --- p.48 / Chapter 3.2.2.4 --- Fluorochrome microscopy --- p.49 / Chapter 3.2.3 --- Tendon-to-tendon healing --- p.49 / Chapter 3.2.3.1 --- Gross anatomy --- p.49 / Chapter 3.2.3.2 --- Microscopic examination --- p.49 / Chapter 3.2.3.3 --- Polarised light microscopy --- p.50 / Chapter 3.3 --- Mechanical testing --- p.50 / Chapter 3.3.1 --- Bone-to-bone healing --- p.50 / Chapter 3.3.1.1 --- Change of cross sectional area --- p.50 / Chapter 3.3.1.2 --- Load at failure --- p.50 / Chapter 3.3.1.3 --- Strength --- p.51 / Chapter 3.3.1.4 --- Energy --- p.51 / Chapter 3.3.2 --- Bone-to-tendon healing --- p.51 / Chapter 3.3.2.1 --- Change of cross sectional area --- p.51 / Chapter 3.3.2.2 --- Load at failure --- p.52 / Chapter 3.3.2.3 --- Strength --- p.52 / Chapter 3.3.2.4 --- Energy --- p.52 / Chapter 3.3.3 --- Tendon-to-tendon healing --- p.52 / Chapter 3.3.3.1 --- Change of cross sectional area --- p.53 / Chapter 3.3.3.2 --- Load at failure --- p.53 / Chapter 3.3.3.3 --- Strength --- p.53 / Chapter 3.3.3.4 --- Energy --- p.53 / Chapter 3.3.4 --- "Comparison of healing quality among BB, BT, and TT repair" --- p.54 / Chapter 3.3.4.1 --- Change of cross sectional area --- p.54 / Chapter 3.3.4.2 --- Load at failure --- p.54 / Chapter 3.3.4.3 --- Strength --- p.54 / Chapter 3.3.4.4 --- Failure mode --- p.55 / Chapter 4. --- Discussion --- p.102 / Chapter 4.1 --- Use of goat calcaneus-Achilles junction as a bone-tendon reseach model --- p.103 / Chapter 4.2 --- "Bone-to-bone, bone-to-tendon, and tendon-to-tendon fixation" --- p.104 / Chapter 4.3 --- Histological characterization of different healing tissues --- p.105 / Chapter 4.3.1 --- Bone-to-bone healing (Fracture healing) --- p.105 / Chapter 4.3.2 --- Bone-to-tendon healing --- p.106 / Chapter 4.3.3 --- Tendon-to-tendon healing --- p.106 / Chapter 4.3.4 --- Regeneration versus repair --- p.107 / Chapter 4.4 --- Spatial and temporal expression of different type of collagen in different form of healing --- p.108 / Chapter 4.5 --- Mechanical properties of healing interface under different form of fixation --- p.108 / Chapter 4.5.1 --- Failure mode --- p.110 / Chapter 4.6 --- Limitations --- p.111 / Chapter 4.6.1 --- Goat animal model --- p.111 / Chapter 4.6.2 --- Immunohistochemistry --- p.111 / Chapter 4.7 --- Future study --- p.112 / Chapter 5. --- Conclusion --- p.113 / Chapter 6. --- References --- p.116

The Ectodysplasin/Ectodysplasin receptor (Eda/Edar) signalling pathway is critical during development for the formation of skin appendages. However, its roles during adulthood are only recently being elucidated. Adult appendages, such as hair follicles (HFs), are known to become activated to respond to cutaneous injury. However, the HF houses distinct cell populations that display differing capacities to participate and persist in re-epithelialisation. We show, contrary to previous findings, that the best-characterised stem cell (SC) niche within the HF (the bulge) does not respond to injury during the earliest stages of wound healing. We propose that bulge SCs are prevented from participating in early repair as a protection mechanism against tumourigenesis. Despite the bulge niche not participating in early repair, we found the upper HF outer root sheath (ORS) to respond rapidly to injury. Our investigation into the role of Eda/Edar signalling during wound healing revealed that activation of the pathway was able to specifically induce proliferation within this portion of the HF. We further demonstrate a number of roles for the Eda/Edar pathway during adult wound healing, including, surprisingly, influencing several wound responses within the dermis. Specifically, an absence of Eda/Edar signalling in Tabby mice results in delayed wound healing, whereas acute activation of the pathway in wild-type (WT) mice can stimulate re-epithelialisation and enhance wound repair. These effects also translate to a model of human wound healing, where activation of Eda/Edar signalling accelerates re-epithelialisation and increases peri-wound proliferation. RNA-seq analysis reveals diverse gene regulation in the presence/absence of Eda/Edar signalling. Overall, these findings suggest that manipulation of the Eda/Edar pathway may represent an attractive potential therapeutic for enhancement of wound repair, potentially through maximising the natural growth capacity of peri-wound HFs.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Com base na necessidade de obter novas formulaÃÃes mais eficientes e diante das propriedades apresentadas pelas molÃculas oriundas de algas marinhas, acredita-se que estas possam ser eficazes no processo de cicatrizaÃÃo. A lectina da alga marinha vermelha Pterocladiella capillacea (PcL) e os polissacarÃdeos da alga vermelha Solieria filiformis (SfP) inicialmente foram analisados em ensaio de toxicidade. PcL foi aplicada no ensaio do edema de pata seguido da dosagem de mieloperoxidase (MPO). Avaliou-se o efeito da lectina da alga Pterocladiella capillacea (PcL) e os polissacarÃdeos das algas Solieria filiformis (SfP) na cicatrizaÃÃo de feridas induzidas em ratos. Ambas as molÃculas foram submetidas a ensaios microbiolÃgicos e analisadas quanto ao efeito no processo de cicatrizaÃÃo em feridas limpas induzidas no dorso de ratos. SfP foi utilizado como um possÃvel veÃculo para a administraÃÃo de PcL e comparado ao Carbopol 940 (C). Os gÃis (0,9%) foram submetidos a anÃlise reolÃgica e entÃo aplicados nas lesÃes durante um perÃodo de tratamento de 10 (dez) dias, utilizando kollagenase como controle. O processo de cicatrizaÃÃo foi avaliado quanto ao tamanho das feridas, dosagem de MPO e anÃlise histolÃgica. PcL e SfP nÃo demonstraram toxicidade quanto aos parÃmetros de peso corpÃreo, ÃrgÃos e dosagens bioquÃmicas. Entretanto a anÃlise histolÃgica mostrou pequenas alteraÃÃes no fÃgado e rim. PcL (1, 3 e 9 mg/kg, i.v.) reduziu o edema induzido por carragenana e quando administrada com seu inibidor mucina nÃo foi possÃvel verificar a reduÃÃo do edema o qual foi confirmado pela dosagem de MPO. As duas molÃculas foram aplicadas em ensaios microbiolÃgicos e nÃo inibiram o crescimento de nenhum micro-organismo testado, os quais tambÃm nÃo foram capazes de utilizar SfP como fonte de carbono. A anÃlise reolÃgica mostrou que os SfP utilizados na formulaÃÃo dos gÃis (PcL+SfP e SfP) apresentaram a caracterÃstica de um pseudoplÃstico. A anÃlise macroscÃpica das feridas mostrou uma reduÃÃo da Ãrea da lesÃo nos animais tratados com PcL+SfP e PcL+C (53,5 e 60%, respectivamente) no sexto dia de administraÃÃo. Na anÃlise histolÃgica, nÃo foi observado infiltrado inflamatÃrio acentuado nos tecidos obtidos atà o 4 dia da administraÃÃo dos gÃis (PcL+SfP e PcL+C) e Kollagenase (controle positivo). No 6 dia, os animais nÃo tratados e os tratados apenas com SfP mostraram infiltrado inflamatÃrio. A dosagem de MPO demonstrou reduÃÃo no processo inflamatÃrio nas amostras contendo PcL, cujo resultado corrobora com a anÃlise histolÃgica. Em conclusÃo, PcL auxiliou no reparo de feridas, sugerindo seu uso futuro como uma possÃvel ferramenta para o tratamento de lesÃes. O papel biolÃgico e farmacolÃgico das lectinas e polissacarÃdeos de algas marinhas faz parte de uma Ãrea de estudos ainda pouco explorada, onde muito conhecimento deverà ser investido visto que estas biomolÃculas podem ser promissoras para a indÃstria farmacÃutica. / Based on the need for new formulations that are more efficient and on the properties provided by molecules derived from seaweed, it is believed that these can be effective in healing process. The lectin from the red seaweed Pterocladiella capillacea (PcL) and the polysaccharides of red algae Solieria filiformis (SfP) were initially analyzed in toxicity testing. PcL was applied to the paw edema test followed by measurement of myeloperoxidase (MPO). We evaluated the effect of the seaweed Pterocladiella capillacea lectin (PcL) and algal polysaccharides Solieria filiformis (SfP) in healing wounds in rats induced. Both molecules were submitted to microbiological tests and assayed for the effect on wound healing in wounds clean induced on the back of rats. SfP was used as a possible vehicle for the administration of PcL and compared to Carbopol 940 (C). The gels (0.9%) were analyzed rheological and then applied to the lesions during a treatment period of 10 days, using kollagenase  as control. The healing process was evaluated on the size of the wounds, levels of MPO and histological analysis. The molecule SfP and PcL is not toxic for the parameters of body weight, organ and biochemical measurements. However, the histological analysis showed minor changes in liver and kidney. PcL (1, 3 and 9 mg / kg, i.v) reduced the edema induced by carrageenan and its inhibitor when administered with mucin was not possible to check the reduction of edema which was confirmed by measurement of MPO. The two molecules were used in microbiological assays and not inhibit growth of any microorganism tested and unable to use SfP as carbon source. The rheological analysis showed that the SfP used in the formulation of the gels (PcL+SfP and SfP) had the characteristic of a pseudoplastic. Macroscopic analysis of wounds showed a reduction in lesion area in the animals treated with PCL, PCL+SfP, PCL+C (53.5 and 60% respectively) on the sixth day of administration. In histological analysis, there was no severe inflammatory infiltrate in the tissues obtained until 4th day of administration of the gels (PcL and PcL+SfP, PcL+C) and Kollagenase (positive control). On day 6, the untreated animals and those treated only with SfP showed inflammatory infiltrate. The measurement of MPO showed a reduction in the inflammatory process in the samples containing PcL, whose results corroborate the histological analysis. In conclusion, PcL aid in wound repair, suggesting its use as a possible future tool for the treatment of lesions. The biological and pharmacological role of lectins and polysaccharides of seaweed is part of a study area little explored, where a lot of knowledge should be invested since these biomolecules can be promising for the pharmaceutical industry.