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The recent coronavirus disease (COVID-19) forced pre-university professionals to modify the educational system. This work aimed to determine the effects of pandemic situation on students' access to medical studies by comparing the performance of medical students. We evaluated the performance of students enrolled in a subject taught in the first semester of the medical curriculum in two pre-pandemic academic years (PRE), two post-pandemic years (POST), and an intermediate year (INT) using the results of a final multiple-choice exam. Consistency analysis among periods was performed using the Cronbach alpha coefficient (α), the difficulty index with random effects correction (DI), and the point-biserial correlation index (PB). The five exams were homogeneous and had similar α, DI, and PB difficultness. Performance significantly decreased in POST students compared with PRE students, with a correlation between performance and the academic years (PRE-POST). A significant decrease in the percentage of correct answers was detected in the academic years, with POST students showing lower results than PRE students, but not in the percentage of questions answered incorrectly. Significantly higher percentages of unanswered questions were found among POST students. These results confirm the negative impact of the POST pre-university educational system on the performance of students accessing medical school and suggest that POST students could have a higher degree of uncertainty. Specific education programs should be implemented during the first years of the medical curriculum to tailor this effect and increase students' self-confidence and knowledge, which may be associated with confidence., (© 2025 The Author(s). Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: Human artificial corneas (HAC) generated by tissue engineering recently demonstrated clinical usefulness in the management of complex corneal diseases. However, the biological mechanisms associated to their regenerative potential need to be elucidated., Methods: In the present work, we generated HAC using nanostructured fibrin-agarose biomaterials with cultured corneal epithelial and stromal cells, and we compared the structure and histochemical and immunohistochemical profiles of HAC with control native corneas (CTR-C) and limbus (CTR-L) to determine the level of biomimicry of the HAC with these two native organs., Results: HAC tissues consisted of a stratified epithelium and a cellular stromal substitute. The interface between stroma and epithelium was similar to that of CTR-C, without the finger-shaped palisades of Vogt found in CTR-L, and contained a poorly developed basement membrane as determined by PAS histochemistry. Analysis of the stromal layer revealed that HAC contained significantly lower amounts of extracellular matrix components (collagen, proteoglycans, decorin, keratocan, and lumican) than CTR-C and CTR-L, with all samples being devoid of elastic and reticular fibers. At the epithelial level, HAC were strongly positive for several cytokeratins, although KRT5 was lower in HAC as compared to CTR-C and CTR-L. The expression of crystallin lambda was lower in HAC than in control tissues, whereas crystallin alpha-a was similar in HAC and CTR-C. No differences were found among HAC and controls for the cell-cell junction proteins CX43 and TJP1. When specific markers were analyzed, we found that HAC expression profile of KRT3, KRT19, KRT15, and ΔNp63 was more similar to CTR-L than to CTR-C., Conclusions: These results suggest that HAC generated in the laboratory could be structurally and functionally more biomimetic to the structure found at the corneal limbus than to the central cornea, and open the door to the use of these artificial tissues in patients with limbal deficiency., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Skin damage due to severe burns can compromise patient life. Current tissue engineering methods allow the generation of human skin substitutes for clinical use. However, this process is time-consuming, as the keratinocytes required to generate artificial skin have a low proliferation rate in culture. In this study, we evaluated the pro-proliferative effects of three natural biomolecules isolated from olive oil: phenolic extract (PE), DL-3,4-dihydroxyphenyl glycol (DHFG), and oleuropein (OLP), on cultured human skin keratinocytes. The results showed that PE and OLP increased the proliferation of immortalized human skin keratinocytes, especially at concentrations of 10 and 5 µg/mL, respectively, without altering cell viability. In contrast, DHFG did not produce a significant improvement in keratinocyte proliferation. In normal human skin keratinocytes obtained from skin biopsies, we found that PE, but not OLP, could increase the number of keratinocyte colonies and the area occupied by these cells. Furthermore, this effect was associated with increased KI-67 and Proliferating cell nuclear antigen (PCNA) gene expression. Thus, we propose that PE positively affects keratinocyte proliferation and could be used in culture protocols to improve bioartificial skin generation by tissue engineering., Competing Interests: Declaration of Competing Interest Authors declare that they do not have any conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Development of an ideal biomaterial for clinical use is one of the main objectives of current research in tissue engineering. Marine-origin polysaccharides, in particular agaroses, have been widely explored as scaffolds for tissue engineering. We previously developed a biomaterial based on a combination of agarose with fibrin, that was successfully translated to clinical practice. However, in search of novel biomaterials with improved physical and biological properties, we have now generated new fibrin-agarose (FA) biomaterials using 5 different types of agaroses at 4 different concentrations. First, we evaluated the cytotoxic effects and the biomechanical properties of these biomaterials. Then, each bioartificial tissue was grafted in vivo and histological, histochemical and immunohistochemical analyses were performed after 30 days. Ex vivo evaluation showed high biocompatibility and differences in their biomechanical properties. In vivo, FA tissues were biocompatible at the systemic and local levels, and histological analyses showed that biointegration was associated to a pro-regenerative process with M2-type CD206-positive macrophages. These results confirm the biocompatibility of FA biomaterials and support their clinical use for the generation of human tissues by tissue engineering, with the possibility of selecting specific agarose types and concentrations for applications requiring precise biomechanical properties and in vivo reabsorption times.

In the present work, we evaluated the potential of maslinic acid (MA) to improve currently available keratinocyte culture methods for use in skin tissue engineering. Results showed that MA can increase cell proliferation and WST-1 activity of human keratinocytes after 24, 48, and 72 h, especially at the concentration of 5 μg/ml, without affecting cell viability. This effect was associated to a significant increase of KI-67 protein expression and upregulation of several genes associated to cell proliferation (PCNA) and differentiation (cytokeratins, intercellular junctions and basement membrane related genes). When human keratinocytes were isolated from skin biopsies, we found that MA at the concentration of 5 μg/ml significantly increased the efficiency of the explant and the cell dissociation methods. These results revealed the positive effects of MA to optimize human keratinocyte culture protocols for use in skin tissue engineering., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ortiz-Arrabal, Chato-Astrain, Crespo, Garzón, Mesa-García, Alaminos and Gómez-Llorente.)

Because cartilage has limited regenerative capability, a fully efficient advanced therapy medicinal product is needed to treat severe cartilage damage. We evaluated a novel biomaterial obtained by decellularizing sturgeon chondral endoskeleton tissue for use in cartilage tissue engineering. In silico analysis suggested high homology between human and sturgeon collagen proteins, and ultra-performance liquid chromatography confirmed that both types of cartilage consisted mainly of the same amino acids. Decellularized sturgeon cartilage was recellularized with human chondrocytes and four types of human mesenchymal stem cells (MSC) and their suitability for generating a cartilage substitute was assessed ex vivo and in vivo. The results supported the biocompatibility of the novel scaffold, as well as its ability to sustain cell adhesion, proliferation and differentiation. In vivo assays showed that the MSC cells in grafted cartilage disks were biosynthetically active and able to remodel the extracellular matrix of cartilage substitutes, with the production of type II collagen and other relevant components, especially when adipose tissue MSC were used. In addition, these cartilage substitutes triggered a pro-regenerative reaction mediated by CD206-positive M2 macrophages. These preliminary results warrant further research to characterize in greater detail the potential clinical translation of these novel cartilage substitutes.

Five agarose types (D1LE, D2LE, LM, MS8 and D5) were evaluated in tissue engineering and compared for the first time using an array of analysis methods. Acellular and cellular constructs were generated from 0.3-3%, and their biomechanical properties, in vivo biocompatibility (as determined by LIVE/DEAD, WST-1 and DNA release, with n = 6 per sample) and in vivo biocompatibility (by hematological and biochemical analyses and histology, with n = 4 animals per agarose type) were analyzed. Results revealed that the biomechanical properties of each hydrogel were related to the agarose concentration ( p < 0.001). Regarding the agarose type, the highest ( p < 0.001) Young modulus, stress at fracture and break load were D1LE, D2LE and D5, whereas the strain at fracture was higher in D5 and MS8 at 3% ( p < 0.05). All agaroses showed high biocompatibility on human skin cells, especially in indirect contact, with a correlation with agarose concentration ( p = 0.0074 for LIVE/DEAD and p = 0.0014 for WST-1) and type, although cell function tended to decrease in direct contact with highly concentrated agaroses. All agaroses were safe in vivo, with no systemic effects as determined by hematological and biochemical analysis and histology of major organs. Locally, implants were partially encapsulated and a pro-regenerative response with abundant M2-type macrophages was found. In summary, we may state that all these agarose types can be safely used in tissue engineering and that the biomechanical properties and biocompatibility were strongly associated to the agarose concentration in the hydrogel and partially associated to the agarose type. These results open the door to the generation of specific agarose-based hydrogels for definite clinical applications such as the human skin, cornea or oral mucosa.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue., (© 2021 S. Karger AG, Basel.)