Estudo de adesão e proliferação celular sobre superfícies de filmes poliméricos modificados por processo de plasma frio com descarga de barreira dielétrica

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química.Este trabalho descreve a síntese de filmes poliméricos, sua modificação e a avaliação quanto à adesão de espécies celulares. Filmes de poliestireno (PS) e poli (metacrilato de metila) (PMMA) e mistura com 1:1 de composição preparados por casting foram avaliados quanto ao crescimento e proliferação de fibroblastos L-929. Estudos envolvendo modificação da superfície destes polímeros foram desenvolvidos, com resultados promissores decorrentes da utilização de plasma frio através de descarga de barreira dielétrica (DBD) para induzir a modificação da superfície, após planejamento fatorial das condições experimentais. Alterações nas propriedades da superfície com relação às amostras não tratadas foram acompanhadas por medidas de ângulo de contato, energia de superfície, histerese, microscopia eletrônica de varredura (SEM) e SEM com espectrometria de energia dispersiva, microscopia de força atômica (AFM) e espectrometria fotoeletrônica de raios-X. Após o tratamento, excelente aderência e proliferação de células foram observadas em todos os filmes com maior proliferação celular no filme PS/PMMA 1:1. Filmes finos de zeína obtidos por spin coating foram também tratados por plasma frio com DBD. Após o tratamento, uma pequena variação de molhabilidade foi detectada, além de aumento de rugosidade. A adsorção de albumina de soro bovino na superfície dos filmes foi também avaliada. Todos os filmes apresentaram excelente adesão das células L-929 após os dois tratamentos. Resultados preliminares para filmes finos nanoestruturados formados a partir de dois copolímeros em bloco de poliestireno e poli(ácido acrílico) são também descritos. Ambos os filmes, após análise por AFM, apresentaram superfícies mais rugosas e uma significativa melhora na adesão e proliferação das células L-929, o que os torna potenciais biomateriais para aplicação biomédica.This work describes the synthesis of polymeric films, their surface modification and an evaluation of their ability to promote adhesion of cell species. Films formed with the casting technique from poly(styrene) (PS), poly (methyl methacrylate) (PMMA) and a 1:1 mixture of both were evaluated towards the growth and proliferation of L-929 fibroblasts. Studies involving the surface modification of the polymeric films were carried out, with promising results obtained from the use of cold plasma generated by a dielectric barrier discharge (DBD), following a factorial design for optimization of the operating parameters. Changes in the surface properties of the plasma-treated films were evaluated by means of contact angle, surface energy and hysteresis measurements, scanning electron microscopy (SEM) and energy-dispersive SEM, atomic force microscopy (AFM) and X-ray photoelectronic spectrometry. Substantial proliferation of cells was observed on the surface of all plasma-treated films, with a superior performance of the PS/PMMA 1:1 film. Thin films produced from zein using the spin coating technique were also submitted to DBD-cold plasma treatment. A minor variation in the wetability of the plasma-treated films was observed, in addition to increased rugosity. The effect of adsorption of bovine serum albumin on the polymeric film surface was also evaluated. Both surface-based treatments resulted in enhanced adhesion of L-929 cells on the polymeric films. Preliminary results for nanostructured thin films formed from two block copolymers of poly(styrene) and poly(acrylic acid) are also presented. AFM analysis of the surface of both plasma-treated films evidenced increased rugosity, which was accompanied by a substantial improvement in the adhesion and proliferation of L-929 cells, turning these polymeric films into promising biomaterials

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030