A bone tissue engineering approach based on the combination of biomimetic scaffolds and flow perfusion culture.

Bone tissue engineering has progressively emerged as a response to the current limited replacement therapies for damaged or lost bone tissue. Ideally, the implanted construct should aid in complete bone regeneration in a reasonably short time, without causing significant inconvenience to the patient. General tissue engineering approaches are based on three different bioactive factors: scaffolding, a cellular component, and a molecular component. These factors are closely conjoined to create successful constructs and fit into a bone tissue engineering paradigm that includes the extraction of a cellular biopsy from a healthy site of the patient. Cells are then expanded in vitro and seeded onto the scaffold. The cell-scaffold construct is cultured under mechanical and/or chemical stimuli for a certain amount of time so as to allow the in vitro secretion of a bone-like extracellular matrix (ECM). This construct, which now possesses an osteoinductive nature due to the secreted ECM, is implanted in the defective site for bone regeneration. The main objective of the present research project was to create an integral tissue engineering approach that combines both mechanical and chemical stimulation by. To fulfill this goal, four major steps were successfully carried out. First, a dynamic scaffold seeding technique based on oscillatory flow perfusion that improved initial cellular distribution throughout the scaffold surface, and cell-matrix interactions was developed. Secondly, a biomimetic poly(L-lactic acid scaffold) with improved cell adhesion using RGD peptides that could additionally allow the evaluation of the effect of different modification levels on cell adhesion, proliferation and differentiation was created. Thirdly, the oscillatory flow perfusion seeding of these RGD-modified scaffolds was characterized. And lastly, the effect of the level of RGD scaffold modification on the osteoblastic differentiation of mesenchymal stem cells when cultured under conditions of flow perfusion was evaluated. What makes this approach unique is the combination of mechanical and chemical stimulation of mesenchymal stem cells to direct them towards an osteoblastic path. This combinatorial approach resulted more successful than those based on chemical or mechanical stimulation alone

Estudio de pre-factibilidad técnica y económica de la implementación de una biorrefinería para la conversión de residuos de cáscara de naranja

Orange peel is an abundant organic waste in Ecuador that can be used and transformed into products of high added value. Therefore, this work analyzes the technical-economic pre-feasibility of a biorefinery from orange peel to obtain essential oil, pectin and / or bioethanol. First, several scenarios were compared around the combination of products to be obtained, and it was established that the most convenient one would be obtaining essential oil and pectin, with an annual production of 8.7 and 44.4 tons, respectively. Next, a process was designed for this biorefinery that consists of 3 sections: the pretreatment of raw material, extraction of the oil, and the extraction of pectin. Material and energy balances of the process were carried out, and later, the equipment was selected and sized according to specific methodologies. The process considered the recovery and recirculation of ethanol used in the pectin extraction section to reduce production costs. Finally, an economic analysis was carried out based on the theoretical cost estimates and a catalog cost analysis. It was found that the project is profitable, and that the payback time for the investment would be between 5 and 6 years. Therefore, the implementation of the biorefinery would generate a positive economic, environmental and social impact in the country.La cáscara de naranja es un residuo orgánico abundante en el Ecuador que puede ser aprovechado y transformado en productos de alto valor agregado. Por ello, el presente artículo analiza la pre-factibilidad técnico-económica de una biorrefinería a partir de cáscara de naranja para la obtención de aceite esencial, pectina y/o bioetanol. Primero, se compararon varios escenarios alrededor de la combinación de productos a ser obtenidos, y se estableció que el más conveniente sería la obtención de aceite esencial y pectina, con una producción anual de 8,7 y 44,4 toneladas, respectivamente. A continuación, se diseñó un proceso para esta biorrefinería que consiste en 3 secciones: el pretratamiento de la materia prima, la extracción del aceite, y la extracción de la pectina. Se realizaron los balances de materia y energía del proceso, y posteriormente, se seleccionaron y dimensionaron los equipos de acuerdo a metodologías específicas. El proceso consideró la recuperación y recirculación de etanol empleado en la sección de extracción de pectina para reducir los costos de producción. Finalmente, se realizó un análisis económico a partir de las estimaciones de costos teóricos y un análisis de costos de catálogo. Se encontró que el proyecto es rentable y que el tiempo de recuperación de la inversión estaría entre 5 y 6 años. Por lo tanto, la implementación de la biorrefinería generaría un impacto positivo a nivel económico, ambiental y social en el país

Matrices of Native and Oxidized Pectin and Ferrous Bisglycinate and Their In Vitro Behavior through Gastrointestinal Conditions

Colloidal matrices of native and oxidized pectin were developed to improve iron bioavailability through the digestive tract. Ferrous bisglycinate (Gly-Fe), obtained by precipitation of glycine chelation to Fe2+, was mixed with native and peroxide-oxidized citrus pectin, and subsequently lyophilized. Controls included matrices with iron and glycine without chelation. The resulting samples were characterized through FTIR, SEM, and TGA/DSC before and after in vitro digestion, which was performed in simulated salivary, gastric, and intestinal fluids. During these digestions, swelling capacity and iron release were assessed. All matrix formulations were porous, and while pectin oxidation did not alter architecture, it changed their properties, increasing thermal stability, likely due to greater number of interaction possibilities through carbonyl groups generated during oxidation. This also resulted in lower swelling capacity, with greater stability observed when using the chelated complex. Higher swelling was found in gastric and intestinal fluids. Pectin oxidation also increased retention of the chelated form, contrary to what was observed with unchelated iron. Thus, there is an important effect of pectin oxidation combined with iron in the form of ferrous biglyscinate on matrix stability and iron release through the digestive tract. These matrices could potentially improve iron bioavailability, diminishing organoleptic changes in fortified iron foods

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

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

Auto-Cross-Linking Hydrogels of Hydrogen Peroxide-Oxidized Pectin and Gelatin for Applications in Controlled Drug Delivery

Pectin-based hydrogels for biomedical applications have attracted recent attention due to their low cost, large availability of the materials, and high levels of biocompatibility. Specifically, periodate-oxidized pectin has been combined with chitosan and gelatin to form different structures. However, hydrogen peroxide-mediated oxidation of pectin has not been studied for this application; furthermore, there is little information on the effect of the degree of oxidation on hydrogel characteristics nor has the feasibility of these systems as controlled drug delivery matrices been explored. Thus, the present work proposes to study the properties of gelatin-peroxide-oxidized pectin hydrogels as drug delivery systems in wound dressing applications. Combinations of pectin at different degrees of oxidation (high, low, and native pectin) and gelatin were analyzed and tested by swelling properties, reswelling from xerogel and aerogel forms, SEM, FTIR, and drug release. It was determined that hydrogels that contained oxidized pectin had improved swelling ratios and stability, at 32°C, compared to those with native pectin and only gelatin. The porosity of the oxidized pectin hydrogels allowed to have sustained and high release rates, which would make them an attractive alternative for wound dressings