The regulated differentiation and polarisation of macrophages are essential for successful wound healing process. During wound repair, macrophages are involved in the early inflammatory process of healing, as well in later regenerative phases by producing cytokines and growth factors relevant for each stage. Their plasticity made macrophages able to change their phenotype from M1 inflammatory during the inflammatory phase of healing to M2 reparative during regenerative phases of healing. Diabetes affects the ability of macrophages to mature from the bone marrow and on their ability to polarise to different phenotypic subsets. Whereas the non-diabetic macrophages can mature normally to M2 macrophages during mid-stages of healing, diabetic wound continues o display immature proinflammatory macrophages resulting in mixed M1/M2 macrophages in the wound that remain until late stages of healing. We previously showed that sustained expression of Hoxa3 reduced the-the excessive number of leukocytes recruited to the wound, suggesting an anti-inflammatory effect of Hoxa3 upon all leukocytes population. Hoxa3 protein transduction also promoted the differentiation of HSC/P into pro-angiogenic Gr1+CD11b+ myeloid cells. Here we showed that Hoxa3 promoted the differentiation of macrophages and upregulated the transcriptional machinery controlling macrophage differentiation, in THP-1 monocytes and primary macrophages from non-diabetic and diabetic mice. Using qRT-PCR and protein analysis of bone marrow derived macrophages from diabetic mice, we showed that Hoxa3 upregulated the master regulator of macrophages differentiation, Pu.1 transcriptionally and post- transcriptionally and that Hoxa3 protein interacted with Pu.1 protein in vitro and in vivo within macrophages proposing a mechanism of their regulation. Hoxa3 also inhibited proinflammatory markers in classically activated macrophages and augmented pro-healing markers in alternatively activated macrophages. Investigating the IL-4/Stat6 pathway of M2 macrophage activation revealed that Hoxa3 upregulated Stat6 and increased Stat6 phosphorylation, a novel effect of Hoxa3 on the signaling pathway of alternative macrophage activation. In vivo analysis of Hoxa3's effect on wound derived macrophages in diabetic mice, confirmed that Hoxa3 promoted the generation of pro-healing macrophages and showed reduced Nos2+ (M1) cells and increased Arg1+ (M2) cells suggesting that Hoxa3 can rescue the phenotype of diabetic macrophages in the wound. Altogether, this work has delineated the specific role of Hoxa3 in rescuing maturation and phenotype of diabetic macrophages thereby providing a better understanding of the therapeutic role of this transcription factor for myeloid cells dysregulation in diabetes.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING / Includes bibliographical references. / by Elizabeth Hsiu-Yun Chen. / M.S.

Orientador: Valdir Gouveia Garcia / Resumo: O objetivo do estudo foi avaliar, histológicamente e biometricamente, a influência da associação de diferentes comprimentos de onda de lasers em baixa intensidade, sobre o processo de reparo em feridas cutâneas abertas provocadas no dorso de ratos. Foram utilizados 72 ratos, os quais foram divididos em 3 grupos com 24 animais cada, sendo: Grupo I - controle (sem tratamento); Grupo II (tratamento com laser 685 nm) e grupo III (tratamento com laser 685 seguido do laser 780 nm na mesma sessão). O laser foi utilizado de modo contínuo e em contato de forma pontual, ponteiras de 50 mW, durante 80 s, nas feridas do grupo II e 40 s (laser 685 nm ) mais 40 segundos (laser 780 nm) nas do grupo III, totalizando 4 J de energia e densidade energética de 200 J/cm2 em ambos os grupos. O diâmetro das feridas foram medidas em 0 h, 3, 7 e 14 d de pós-operatório e, os dados foram submetidos à análise estatística. Nos intervalos de 3, 7 e 14 d, 8 animais de cada grupo foram sacrificados e as peças foram submetidas a processamento histológico e coradas pela técnica da hematoxilina e eosina e tricrômico de Massom. Concluiu-se: 1) Grupo II e III evidenciaram resultados histológicos mais diferenciados que Grupo I; 2) Grupo III demonstrou reparação mais diferenciada que o Grupo I e o Grupo II; 3) do ponto de vista biométrico, o maior grau de contração foi observado nas feridas do Grupo III, seguido das do grupo II e I, no período de 14 dias. / Abstract: This investigation aimed to study, histologically, the influence of association of different wave-length of low intensity laser on the healing process in cutaneous wound provoked at the dorsum of rats. Seventy-two rats, 3 groups of 24 animals each, were used, namely: Group I - control (without treatment); Group II (treatment with laser of 685 nm) and Group III (treatment with laser of 685 nm associated with laser of 780 nm in the same session). In Group II, the laser was applied continuously with a point of contact of 50 mW during 80 s. In Group III, the laser of 685 nm was applied and, followed with laser of 780 nm for 40 s in each application. A total of 4 J of energy and 200 J/cm2 of energetic density were applied in both groups. The diameter of the wound was measured at baseline, 3, 7 and 14 post-operative days and the results were submitted to statistical analysis. At intervals of 3, 7 and 14 days, 8 animals of each group were sacrificed and the pieces were submitted to histological processing and were stained by hematoxiline and eosine and Massom's tricromic techniques. It was concluded that: 1) Group II and III showed histological results statistically different from Group I; 2) Group III demonstrated a statistically differentiated healing in comparison to Group I and II; 3) at the point of view of biometrics, the greatest degree of contraction was observed in Group III, followed by Group II and I, at the period of 14 days. / Mestre

Diante da indisponibilidade de um instrumento específico de avaliação da qualidade de vida (QV) de pessoas com qualquer tipo de ferida, em nosso meio, o objetivo deste estudo foi construir e validar a versão feridas do Índice de Qualidade de Vida de Ferrans e Powers (IQVFP-VF). Inicialmente, o estudo recebeu autorização das autoras do instrumento original, aprovação pelo Comitê de Ética da EEUSP e autorizações dos campos para a coleta de dados. Classificado como do tipo metodológico, o estudo foi desenvolvido segundo os procedimentos teóricos, empíricos e analíticos, propostos por Pasquali, Os procedimentos teóricos incluíram a definição e análise dos itens por meio de revisão de literatura, avaliações de juizes (especialistas e pacientes) e pré-teste; os empíricos foram realizados por meio da aplicação do instrumento, resultante da etapa anterior, para análise de suas propriedades psicométricas, em amostras de teste (n=362), re-teste (n = 63) e validade convergente (n=179); e os analíticos, por meio das estratégias estatísticas destinadas às análises das propriedades psicométricas do instrumento final dos procedimentos teóricos. A confiabilidade foi obtida por meio da avaliação da consistência interna - CI (alfa de Cronbach 0,70) e da estabilidade do instrumento - duas semanas pós-teste (coeficiente de correlação intraclasse 0,70). Avaliaram-se a validade de conteúdo, pela concordância entre juizes ( 80%); a de critério concorrente, pela correlação entre os escores do item sua satisfação e dos domínios e instrumento total (coeficiente de correlação de Pearson ou Spearman 0,30); a validade de construto convergente, correlacionando-se os domínios e instrumento total do IQVFP-VF e WHOQOL-bref (esperando-se correlações moderadas a fortes 0,30 entre os domínios similares e < 0,30 entre os diferentes) e a validade de construto discriminante, comparando-se os escores dos domínios e instrumento total quanto a idade, número e duração da ferida e intensidade de dor, no momento e na última semana (Testes de Mann-Whitney, Kruskal-Wallis, t-Student e ANOVA). A análise fatorial confirmatória (AFC) foi testada pelo grau de correlação entre os itens e os domínios originais (saúde/funcionamento-SF; sócio-econômico-SE; psicológico e espiritual-PE e família-Fa) e medidas de ajuste de modelo (LISREL). A amostra foi composta de pacientes ambulatoriais com feridas, pertencentes a dezesseis instituições, que se enquadraram em critérios pré-estabelecidos. Os resultados mostram coeficientes alfa de Cronbach 0,90; 0,88; 0,65; 0,81; 0,55 para o instrumento total e domínios SF, SE, PE, Fa respectivamente, na avaliação da CI; para a estabilidade, encontraram-se correlações 0,83 (p < 0,000); para a validade concorrente, correlações de 0,28 a 0,69; para a validade convergente, correlações de 0,17 a 0, 60 e para a validade discriminante, correlações significativas entre: QV geral e número de feridas (p=0,047); PE e duração da ferida (p=0,017); SF (p= 0,043), SE (p= 0,008), PE (p= 0,000) e qualidade de vida geral (p=0,003) para as faixas etárias mais avançadas; e SE e a pior dor da semana anterior à entrevista (p = 0,015). À AFC sugeriu que o modelo é razoavelmente ajustado para o quatro domínios. Concluindo-se o estudo, pode-se considerar que o IQVFP-VF - como um instrumento específico e relacionado à saúde - é válido e tem confiabilidade atestada nos aspectos mais importantes para a população com feridas: a QV geral, a saúde e os aspectos psicológicos e espirituais / The scarcity of a specific tool to evaluate the quality of life (QOL) of persons with any kind of wounds, in our culture, lead to the development of this study. It aimed to develop and validate a wound version of the Ferrans & Powers QOL Index (QLI -WV). The study was authorized by the QLI authors and was approved by the Ethics Committee of Nursing College of the University of São Paulo and authorized by the institutions where data were collected. This methodological research was based on the procedures established by Paquali. The theoretical pole included the selection and analysis of the items to be included in the instrument (literature review, evaluations by specialists and patients committees and pre test). The empirical ones were developed through the application of the resulted instrument (from last step) to test sample (n=362), teste-retest sample (n=63) and convergent validity sample (n=179). And the analytical pole included the statistical strategies to analyse the instrument´s psychometric properties. The reliability was obtained through: internal consistency - IC (Cronbach´s alpha 0,70) and stability, two weeks after the first instrument apllication (Intraclass correlation coeficient 0,70). The content validity was analysed through the concordance level between judges ( 80%); the concurrent validity, through the correlation among the scores of the item your satisfaction and domains and overall QOL (Pearson or Spearman correlation coeficient 0,30); the convergent validity, through the correlation between the domains and overall QOL of QLI -WV and WHOQOL-bref (strong to moderate correlation between similar domains and weak between the different ones) and the discriminant validity through the comparison among the domains and total QOL and age, wound number and durability, and present and the worst last week pain (Mann Whitney, Kruskal-Wallis, t-Student and ANOVA tests). The confirmatory factor analysis (CFA) was tested by the correlation between the QLI-WV items and original domains (health & functioning - HF; socioeconomic - SE, psychological/spiritual - PS and family - Fa) and the adjustment measures model (LISREL). The sample was composed by outpatients who were assisted at 16 Health Services, and who met the pre established criteria. The results showed Cronbach´s alpha coeficients of 0.90; 0.88; 0.65; 0.81; 0.55 respectively for total QOL and domains (HF, SE, PS and Fa) for IC; r 0.83 (p < 0.000) for stability; r = 0.28 to 0.69 for concurrent validity; r = 0.17 to 0. 60 for convergent validity and significative correlation between: overall QOL and number of wounds (p=0.047); PS and wound durability (p=0.017); HF (p= 0.043), SE (p= 0.008), PS (p= 0.000) and overall QOL (p=0.003) for old patients; and SE and worst last week pain (p = 0.015). CFA suggested a reasonable fit for a four original subscale. The author concludes that QLI-WV - as a specific and health related QOL instrument - can be considered reliable and valid as it confirmed their psychometric properties, related to the most important wound care aspects as the total QOL, health and psychological and spiritual issues

Wound treatment is a significant field in healthcare, but one with huge potential and need for advancement. Infection monitoring, in its current state, is a largely primitive affair, relying on visual and olfactory inspection to detect bacteria. As a result, early detection is impossible, and doctors and patients are forced to remove dressings to investigate the wound in a laborious, painful, and unsanitary process. When an infection is detected, the treatment is typically systemic administration of antibiotics. Systemic administration reduces the concentration of antibiotics that can be brought to bear on the infection because it interacts with the entire body and is dissipated by the time it reaches the wound and increases the risk of side effects or antibiotic resistance. Within this thesis, a smart, thread-based wound dressing is presented that addresses these issues by providing a pH-based early detection system accompanied by a topical, on-demand drug delivery system. The device has been tested in vitro and in vivo, on bacterial culture and on an animal model, and demonstrated effectiveness at detecting and eliminating bacteria, and at promoting wound healing. This smart wound dressing has the potential to improve treatment and outcomes for a wide variety of injuries, varying from burns to chronic wounds. / Graduate / 2020-10-10

This research project investigated the impact of an action research intervention implemented to reducing surgical wound infection in one of the acute care hospitals in India. The study aimed to develop and implement a clinical practice improvement program in reducing surgical wound infection by improving the hand washing and wound dressing practices of nurses. The study also aimed to identify the important contributing factors to a model that predicts surgical wound infection. Pre-post evaluation measures were taken to compare the results of surgical wound infection rate before and after the implementation of the intervention. Surgical wounds of two thousand patients (one thousand before the intervention and another one thousand after) were assessed to determine the wound infection rate and severity of wound infection. The hand washing and wound dressing practices of forty nurses were observed. These same nurses were involved in the intervention using a participatory action research process. The results of the study suggest that there was a marked, significant reduction in the rate and severity of wound infection following the implementation of the intervention. By increasing the hand washing facilities in the ward, educating nurses on the importance of better hygiene, pre-operative shaving and post-operative wound care, the hand washing and wound dressing practices of nurses improved considerably. These improvements resulted in a reduction in the number and severity of patients' surgical wound infections. The study also examined the contribution of different factors to surgical wound infection in a Indian hospital. Significant predictive factors were the patients' age, longer pre-operative hospital stay, extended pre-operative shaving time before surgery, wound class, and co-morbidity of the patient. The identification of risk factors that contributed to increased surgical wound infection for example pre-operative skin preparation, pre-operative hospital stay of the patient would help in taking appropriate measures at the ward level and organisation as a whole. Nosocomial infections extends to an unnecessary lengthy hospital stay, additional treatment increased mortality and morbidity, and increased cost to the patients and the nation as a whole. This project proved that educational mentoring, data surveillance processes and involving the nurses in an action research process were effective in enabling participants to improve their clinical practice and thereby reduce the incidence of patients' surgical wound infections. Establishing infection control teams, ongoing surveillance and feedback to staff of nosocomial infection rates is an urgent need in all Indian hospitals. Organisational management, as a priority, need to provide funding and staff dedicated to undertaking this essential work. Health care professionals can no longer plead ignorance of a situation for which all have a moral and professional responsibility.

Purpose: The aim of this thesis was to investigate a suitable formulation for the topical delivery of growth factors to chronic wounds, and then to determine the concentrations reached within an animal wound model. A secondary aim was to determine if the chosen growth factor was present at levels able to stimulate the production of other cytokines, specifically IL-1β and MCP-1. Methods: An in vitro testing apparatus was designed and made and the release of model actives [bromophenol blue (BPB) and horseradish peroxidase (HRP)] from gels and films of hydroxylpropylmethylcellulose (HPMC) (E4M CR, K4M CR and E10M CR) was determined. In this study, Fibroblast Growth Factor -2 (FGF-2) (0.3 [mu]g) was incorporated into three formulations (solution, gel and dried gel film on Melolin[TM] backing) and together with a control formulation were administered to punch biopsy wounds in rats. The in vivo release was followed over three time periods (two, five and eight hours) and the amount of FGF-2 at various wound depths was quantified by ELISA. Two biological markers IL-1β and MCP-1 were quantified using ELISA. The FGF-2 was additionally tagged with a fluorescent dye so that visualisation of the penetration could be obtained via confocal microsopy. Results: For the HPMC gels, the more viscous gel (E10M) provided a greater diffusional barrier and slowed the release of BPB (12 � 3.5 [mu]g/min compared with 16 � 1.7 [mu]g/min and 18 � 1.4 [mu]g/min for K4M and E4M respectively). However, when HPMC was formulated as a dried film a burst release was seen and release of BPB was slowest from the more rapidly hydrating K4M. With the larger model active HRP, there was a slower diffusion through the gel barrier formed upon film hydration, such that time of 100% release was up to 300 minutes compared to approximately 60 minutes for BPB. When the film was dried onto a supportive backing, the initial burst release was minimised as the film did not break apart on contact with the wound, and hence film integrity was maintained and release prolonged. The in vivo studies showed that, two hours after application, the highest concentration of FGF-2 was seen in the surface granulation tissue of rats that received the solution formulation (2280 � 790 pg/g). The concentration decreased with increasing tissue depth but was significantly greater than the saline control in the surface granulation and subcutaneous fat layers (p<0.05). Tissue concentrations following application of the gel and film formulations were only marginally greater than control in the surface granulation layer. After eight hours, rats that received the solution retained elevated surface tissue concentrations (surface granulation and subcutaneous fat) of FGF-2. Repeated measures ANOVA using a general linear model showed statistically significant differences in the mean FGF-2 level with respect to formulation and length of time of application of the formulation (p<0.05). In terms of other cytokines, there was a release of both IL-1β and MCP-1 in all groups, immediately post-wounding, probably in response to cellular damage. After eight hours, the film formulation appeared to elevate IL-1β levels which may be useful to drive wound healing. Confocal microscopy images showed diffuse distribution of FGF-2 eight hours after application of the solution formulation after eight hours and that with the gel formulation FGF-2 initially aggregated at the wound surface. Conclusion: In vitro experiments investigating the effect of hydration rate and viscosity of HPLC polymers allowed a formulation to be chosen for further in vivo study. Elevated FGF-2 could be measured in superficial wound tissues up to eight hours after application of a solution. However, application of a comparable amount of FGF-2 in HPMC gels or films did not produce appreciable elevations in FGF-2 in wound tissues, although confocal microscopy indicated the penetration of FGF-2 into the wound for up to eight hours.

"July, 2001" / Addendum inserted in back. / Includes bibliographical references (leaves 250-284) / xxiii, 284 leaves : ill. (some col.), plates (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, 2001

<p>Rapid wound healing is important to regain the skins protective function after injury. Studies have shown that enamel matrix proteins (EMP) have many desirable effects which may accelerate wound healing [Bosshardt <em>et al.</em> 2008].</p><p> </p><p>Polymers (Polymer A, B and C) were formed into a mat form, with or without incorporated enamel matrix derivative (EMD) (Collaboration partner). The materials may be suitable for wound care and drug delivery systems.</p><p> </p><p>Protein release tests were performed on samples incubated in physiological-like solution using pyrogallol red staining, ultraviolet (UV) spectrophotometer and high-performance liquid chromatography (HPLC). Protein was detected in Polymer A material samples, compared to a reference material sample, using pyrogallol red staining. An in vitro experiment showed that normal human dermal fibroblasts (NHDF) cultivated with Polymer A material (with EMD) had significantly higher viability than NHDF cultivated with reference material (Polymer A without EMD) and comparable viability to fibroblasts grown with either 0.1 mg EMD in solution or with 10% fetal calf serum. Images taken of Polymer A material, with incorporated Fluorescein isothiocyanate- (FITC) labeled EMD, indicate a homogenous distribution of EMD peptides and/or EMD aggregates throughout the material. A dressing which contains an active substance may have clinical promise for wound care applications.</p>

<p>Syftet med denna litteraturstudie var att via litteraturen beskriva nutritionens betydelse för sårläkning. Studien genomfördes som en deskriptiv litteraturstudie där metoden bestod av att söka vetenskapliga artiklar i databaserna Medline, Cinahl och Academic Search Elite. Sjutton artiklar valdes ut. Resultatet visade att patienter med bensår eller trycksår i många fall inte når upp till de näringsrekommendationer som finns. Det visade sig vara vanligt att dessa patienter ligger vid gränsen för att vara undernärda. Det upptäcktes att det är sällan som kostintaget täcker energibehovet. Framför allt var zinknivåerna genomgående väldigt låga och det visar även att det är brist på en hel del andra ämnen. Ämnen som visat sig speciellt fördelaktiga för sårläkning är protein, vitamin C, zink samt arginin. För patienter med brännskador däremot har det visat sig att saltet ornithine α-ketoglutarate minskar proteinkatabolismen samt förbättrar proteinsyntesen, vilket är en förutsättning för sårläkning. Slutsatsen med föreliggande studie var att nutritionen är viktig och kan ha en avgörande betydelse för sårläkning.</p> / <p>The purpose with this literature study was that through literature describe the nutrition’s significance for healing wounds. The study was made as a descriptive literature study where the method was conducted by searching scientific articles in the databases Medline, Cinahl and Academic Search Elite. Seventeen articles were chosen. The result showed that patients with leg ulcers or pressure sores in many cases don’t attain the recommendations for nutrition that are available. It showed that it is normal that these patients are on the border of being undernourished. It was discovered that the nutrient intake rarely covers the energy needs. Above all the zinc levels were throughout very low and that shows that there is also lack of some other substances. The substances that have been shown especially good for healing wounds are protein, vitamin C, zinc and arginine. However, for patients with burn injuries the salt ornithine α-ketoglutarate has been shown to reduce protein catabolism and also improve protein synthesis, which are essential to healing wounds. The conclusion from this study was that nutrition may be an important but also a determining factor to healing wounds.</p>