Hybrid organic-inorganic Scaffolding Biomaterials for Regenerative Therapies

The introduction of hybrid materials in regenerative medicine has solved some problems related to the mechanical and bioactive properties of biomaterials. Calcium phosphates and their derivatives have provided the basis for inorganic components, thanks to their good bioactivity, especially in bone regeneration. When mixed with biodegradable polymers, the result is a synergic association that mimics the composition of many tissues of the human body and, additionally, exhibits suitable mechanical properties. Together with the development of nanotechnology and new synthesis methods, hybrids offer a promising option for the development of a third or fourth generation of smart biomaterials and scaffolds to guide the regeneration of natural tissues, with an optimum efficiency/cost ratio. Their potential bioactivity, as well as other valuable features of hybrids, open promising new pathways for their use in bone regeneration and other tissue repair therapies. This review provides a comprehensive overview of the different hybrid organic-inorganic scaffolding biomaterials developed so far for regenerative therapies, especially in bone. It also looks at the potential for research into hybrid materials for other, softer tissues, which is still at an initial stage, but with very promising results

Pre-service teachers’ search strategies when sourcing educational information on the Internet

Teachers need to be able to inform and justify their teaching practice based on available research knowledge. When searching for research knowledge, the Internet plays a crucial role as it allows teachers to search for and access evidence long after their own education at university. On the Internet, however, educational information can have varying levels of scientific groundedness (e.g., science articles or blogs from colleagues), and research indicates that (pre-service) teachers struggle to find, select, and evaluate online educational information. It is precisely for this reason that it is important to educate (pre-service) teachers on how to competently source online information. This study describes pre-service teachers’ search strategies when sourcing online educational information about the topic “students’ use of mobile phones in class.” It sheds light on their use of (1) basic or advanced search strategies and (2) the role of Internet-specific epistemological beliefs (ISEBs). N = 77 pre-service teachers conducted a realistic search on the Internet and selected those web items (WI) that they perceived relevant for justifying whether mobile phones should be used in class. Their sourcing behavior was screen-recorded and analyzed. Most selected WI were found via search engines of Google LLC (91.4%). Advanced search strategies were defined as (1) using two or more search engines (performed by 62.3% of participants), (2) adapting search terms and/or formulating new search terms (90.9%), (3) selecting at least one WI that was not listed among the first four ranks on the first search engine results page (54.7%), and (4) checking for the trustworthiness of the author/source (14.3%) or the quality of the content (13%). Binary logistic regressions were used to analyze the relationship between ISEBs and (1) search strategies and (2) science-relatedness of WI as dependent variables. The predictor ISEB did not contribute to the models, meaning that differences in participants’ ISEBs did not significantly relate to their search strategies nor to the science-relatedness of WI, all β ≤ |0.36|, Wald ≤ 0.64, p ≥ 0.43. The role of pre-service teachers’ search strategies is discussed with respect to teachers’ evidence-informed reasoning and its implications for teacher education.Peer Reviewe

Alteração do processamento auditivo em indivíduos expostos ao ruído ocupacional : revisão sistemática de literatura

A perda auditiva induzida por ruído (PAIR) é a perda progressiva e lenta, devida à exposição contínua a níveis elevados de pressão sonora(85dBNA). A perda auditiva pode ter como consequência prejuízos de diferentes naturezas, como perda parcial e/ou total da audição, disfunções auditivas e alterações vestibulares. Objetivo: descrever e analisar as pesquisas científicas que correlacionem alterações de processamento auditivo e exposição a ruído ocupacional. Métodos: a pesquisa foi feita tendo como base os seguintes descritores e palavras-chave: Noise Induced Hearing Loss” and “Central Auditory Processing”; “Noise Induced Hearing Loss” and “Central Auditory”; “Noise Induced Hearing Loss” and “Auditory Dysfunctions”; “Noise” and “Central Auditory Processing” ; “Noise” and “Central Auditory“ ; “Noise” and “Auditory Dysfunctions”. Foram incluídos, no presente estudo, artigos em português, inglês e espanhol, publicados no período de 1994 a 2014. A busca foi feita nas bases de dados PubMed, Lilacs, Scielo e Ibecs. Como princípio essencial da pesquisa,formulou-se a pergunta: existe alteração do processamento auditivo em indivíduos com perda induzida por ruído? Resultados: após o levantamento bibliográfico, somente três artigos preencheram todos os critérios relevantes para este estudo. Conclusão: concluiu-se que, provavelmente, existe relação entre perda induzida por ruído ocupacional e alterações do processamento auditivo, mas devido a controvérsias observadas nos resultados de alguns estudos, torna-se necessária a realização de novas pesquisas.Noise-induced hearing loss (NIHL) is the slow progressive loss, due to continuous exposure to high levels of sound pressure (85dBNA). Hearing loss can have as a consequence damages of different natures, and may lead to partial and/or total loss of hearing, auditory and vestibular dysfunctions changes. Objective: describe and analyze scientific researches that relate changes of auditory processing and exposure to occupational noise. Methods: The research was made on the basis of the following descriptors and keywords: “Noise Induced Hearing Loss" and "Central Auditory Processing"; "Noise Induced Hearing Loss" and "Central Auditory"; "Noise Induced Hearing Loss" and "Auditory Dysfunctions"; "Noise" and "Central Auditory Processing"; "Noise" and "Central Auditory"; "Noise" and "Auditory Dysfunctions". Were included in the study articles in Portuguese, English and Spanish, published in the period of 1994 to 2014. The search was made in the databases PubMed, Lilacs, Scielo and Ibecs. The essential principle of the research question of this study was: there is change in the auditory processing in individuals with noise-induced loss? Results: After the bibliographic survey in only 3 articles meet all relevant criteria for this study. Conclusion: It was concluded that probably there is relationship between occupational noise-induced loss and changes of auditory processing, but due to controversies seen in results from some studies, it is necessary that new research be made

The generation of a lactate-rich environment stimulates cell cycle progression and modulates gene expression on neonatal and hiPSC-derived cardiomyocytes

In situ tissue engineering strategies are a promising approach to activate the endogenous regenerative potential of the cardiac tissue helping the heart to heal itself after an injury. However, the current use of complex reprogramming vectors for the activation of reparative pathways challenges the easy translation of these therapies into the clinic. Here, we evaluated the response of mouse neonatal and human induced pluripotent stem cell-derived cardiomyocytes to the presence of exogenous lactate, thus mimicking the metabolic environment of the fetal heart. An increase in cardiomyocyte cell cycle activity was observed in the presence of lactate, as determined through Ki67 and Aurora-B kinase. Gene expression and RNA-sequencing data revealed that cardiomyocytes incubated with lactate showed upregulation of BMP10, LIN28 or TCIM in tandem with downregulation of GRIK1 or DGKK among others. Lactate also demonstrated a capability to modulate the production of inflammatory cytokines on cardiac fibroblasts, reducing the production of Fas, Fraktalkine or IL-12p40, while stimulating IL-13 and SDF1a. In addition, the generation of a lactate-rich environment improved ex vivo neonatal heart culture, by affecting the contractile activity and sarcomeric structures and inhibiting epicardial cell spreading. Our results also suggested a common link between the effect of lactate and the activation of hypoxia signaling pathways. These findings support a novel use of lactate in cardiac tissue engineering, modulating the metabolic environment of the heart and thus paving the way to the development of lactate-releasing platforms for in situ cardiac regeneration.Postprint (published version

Microfluidic 3D Platform to Evaluate Endothelial Progenitor Cell Recruitment by Bioactive Materials

Most of the conventional in vitro models to test biomaterial-driven vascularization are too simplistic to recapitulate the complex interactions taking place in the actual cell microenvironment, which results in a poor prediction of the in vivo performance of the material. However, during the last decade, cell culture models based on microfluidic technology have allowed attaining unprecedented levels of tissue biomimicry. In this work, we propose a microfluidic-based 3D model to evaluate the effect of bioactive biomaterials capable of releasing signaling cues (such as ions or proteins) in the recruitment of endogenous endothelial progenitor cells, a key step in the vascularization process. The usability of the platform is demonstrated using experimentally-validated finite element models and migration and proliferation studies with rat endothelial progenitor cells (rEPCs) and bone marrow-derived rat mesenchymal stromal cells (BM-rMSCs). As a proof of concept of biomaterial evaluation, the response of rEPCs to an electrospun composite made of polylactic acid with calcium phosphates nanoparticles (PLA+CaP) was compared in a co-culture microenvironment with BM-rMSC to a regular PLA control. Our results show a significantly higher rEPCs migration and the upregulation of several pro-inflammatory and proangiogenic proteins in the case of the PLA+CaP. The effects of osteopontin (OPN) on the rEPCs migratory response were also studied using this platform, suggesting its important role in mediating their recruitment to a calcium-rich microenvironment. This new tool could be applied to screen the capacity of a variety of bioactive scaffolds to induce vascularization and accelerate the preclinical testing of biomaterials.Peer ReviewedPostprint (published version

The generation of a lactate-rich environment stimulates cell cycle progression and modulates gene expression on neonatal and hiPSC-derived cardiomyocytes

In situ tissue engineering strategies are a promising approach to activate the endogenous regenerative potential of the cardiac tissue helping the heart to heal itself after an injury. However, the current use of complex reprogramming vectors for the activation of reparative pathways challenges the easy translation of these therapies into the clinic. Here, we evaluated the response of mouse neonatal and human induced pluripotent stem cell-derived cardiomyocytes to the presence of exogenous lactate, thus mimicking the metabolic environment of the fetal heart. An increase in cardiomyocyte cell cycle activity was observed in the presence of lactate, as determined through Ki67 and Aurora-B kinase. Gene expression and RNA-sequencing data revealed that cardiomyocytes incubated with lactate showed upregulation of BMP10, LIN28 or TCIM in tandem with downregulation of GRIK1 or DGKK among others. Lactate also demonstrated a capability to modulate the production of inflammatory cytokines on cardiac fibroblasts, reducing the production of Fas, Fraktalkine or IL-12p40, while stimulating IL-13 and SDF1a. In addition, the generation of a lactate-rich environment improved ex vivo neonatal heart culture, by affecting the contractile activity and sarcomeric structures and inhibiting epicardial cell spreading. Our results also suggested a common link between the effect of lactate and the activation of hypoxia signaling pathways. These findings support a novel use of lactate in cardiac tissue engineering, modulating the metabolic environment of the heart and thus paving the way to the development of lactate-releasing platforms for in situ cardiac regeneration.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved

Wound healing-promoting effects stimulated by extracellular calcium and calcium-releasing nanoparticles on dermal fibroblasts

Extracellular calcium has been proved to influence the healing process of injuries and could be used as a novel therapy for skin wound healing. However, a better understanding of its effect, together with a system to obtain a controlled release is needed. In this study, we examined whether the ionic dissolution of the calcium–phosphate-based ormoglass nanoparticles coded SG5 may produce a similar stimulating effect as extracellular calcium (from CaCl2) on rat dermal fibroblast in vitro. Cells were cultured in the presence of medium containing different calcium concentrations, normally ranging from 0.1 to 3.5 mM Ca2+. A concentration of 3.5 mM of CaCl2 increased metabolic activity, in vitro wound closure, matrix metalloproteinases (MMP) activity, collagen synthesis and cytokine expression, and reduced cell contraction capacity. Interestingly, the levels of migration and contraction capacity measured followed a dose-dependent behavior. In addition, media conditioned with SG5 stimulated the same activities as media conditioned with CaCl2, but undesired effects in chronic wound healing such as inflammatory factor expression and MMP activity were reduced compared to the equivalent CaCl2 concentration. In summary, calcium-releasing particles such as SG5 are potential biological-free biostimulators to be applied in dressings for chronic wound healing.Peer ReviewedPostprint (author's final draft

Going South: Tracing Race and Region in the Post-Emancipation Black Atlantic

The demise of American slavery in 1865 put black Americans in motion to an unprecedented degree. Freed slaves and their descendants migrated from the plantations in the rural South to destinations around the globe. Travelling in a variety of new roles – as missionaries, journalists, agronomists, scientists, athletes, performers, entrepreneurs and political activists – African Americans gained international visibility, inspiring other oppressed populations in the colonial world to struggle for their liberation

Oxidación superficial de aleaciones de NiTi para la mejora de la biocompatibilidad

Se han estudiado diferentes tratamientos superficiales con el fin de obtener una capa de TiO2 con una mínima concentración de Ni en la superficie de aleaciones de NiTi 50/50 con memoria de forma: pulido espejo, autoclave, electropulido, oxidación en un baño de agua hirviendo y oxidación térmica en atmósfera controlada de aire. Se analizaron las superficies de las muestras mediante XPS. El tratamiento de oxidación térmica es el que da el ratio Ti/Ni más alto, la menor cantidad de Ni en superficie y también el mayor espesor de óxido. Se comprobó mediante un experimento de liberación de iones que el óxido formado por este proceso de oxidación hace disminuir la liberación de iones Ni al medio fisiológico respecto a la superficie no tratada. Se hicieron estudios de cultivos celulares de osteoblastos de línea MG63 sobre superficies no tratadas y tratadas térmicamente de NiTi. Los resultados de proliferación muestran que, para los días 3, 6 y 9 no existen diferencias estadísticamente significativas entre los materiales. Sin embargo, después de 48h de estimulación para la diferenciación, las células cultivadas sobre las superficies tratadas térmicamente demuestran una mayor actividad de la fosfatasa alcalina y mayores niveles de osteocalcina.Various surface treatments have been studied in order to find the most appropriate in forming a TiO2 with a low Ni content on the surface of equiatomic NiTi alloys. Sample surfaces have been analyzed by XPS. Thermal oxidation treatment in an air-controlled atmosphere leads to the highest Ti/Ni ratio, to the lowest Ni surface concentration and to the thickest oxide layer. It has been shown by the results of ion release experiment that the oxide formed by this oxidation process allows to decrease Ni release into exterior medium comparing with non-treated surfaces. Cell cultures of MG63 osteoblast-like cells have been carried out. The proliferation study shows that from day 3 to day 9 there is no statistically significant differences between negative control, non-treated and thermally oxidized surfaces. After 48h of stimulation for differentiation, MG63 cells on thermally oxidized surfaces show higher phosphatase alkaline activity and osteocalcin level

Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells

Limbal epithelial stem cells (LESCs) are responsible for the renewal of corneal epithelium. Cultivated limbal epithelial transplantation is the current treatment of choice for restoring the loss or dysfunction of LESCs. To perform this procedure, a substratum is necessary for in vitro culturing of limbal epithelial cells and their subsequent transplantation onto the ocular surface. In this work, we evaluated poly-L/DL-lactic acid 70:30 (PLA) films functionalized with type IV collagen (col IV) as potential in vitro carrier substrata for LESCs. We first demonstrated that PLA-col IV films were biocompatible and suitable for the proliferation of human corneal epithelial cells. Subsequently, limbal epithelial cell suspensions, isolated from human limbal rings, were cultivated using culture medium that did not contain animal components. The cells adhered significantly faster to PLA-col IV films than to tissue culture plastic (TCP). The mRNA expression levels for the LESC specific markers, K15, P63α and ABCG2 were similar or greater (significantly in the case of K15) in limbal epithelial cells cultured on PLA-col IV films than limbal epithelial cells cultured on TCP. The percentage of cells expressing the corneal (K3, K12) and the LESC (P63α, ABCG2) specific markers was similar for both substrata. These results suggest that the PLA-col IV films promoted LESC attachment and helped to maintain their undifferentiated stem cell phenotype. Consequently, these substrata offer an alternative for the transplantation of limbal cells onto the ocular surface.This work was supported by the Carlos III National Institute of Health, Spain (CIBER-BBN and Spanish Network on Cell Therapy, (TerCel RD12/0019/0036), MINECO/FEDER, EU), and the Castilla y León Regional Government, Spain (Regional Center for Regenerative Medicine and Cell Therapy, SAN673/VA/28/08 and SAN126/VA11/09)