Although Flaviviruses such as dengue (DENV) and zika (ZIKV) virus are important human pathogens, an effective vaccine or antiviral treatment against them is not available. Hence, the search for new strategies to control flavivirus infections is essential. Several studies have shown that the host lipid metabolism could be an antiviral target because cholesterol and other lipids are required during the replicative cycle of different Flaviviridae family members. FDA-approved drugs with hypolipidemic effects could be an alternative for treating flavivirus infections. However, a better understanding of the regulation between host lipid metabolism and signaling pathways triggered during these infections is required. The metabolic pathways related to lipid metabolism modified during DENV and ZIKV infection are analyzed in this review. Additionally, the role of lipid-lowering drugs as safe host-targeted antivirals is discussed.
The search of suitable combinations of stem cells, biomaterials and scaffolds manufacturing methods have become a major focus of research for bone engineering. The aim of this study was to test the potential of dental pulp stem cells to attach, proliferate, mineralize and differentiate on 3D printed polycaprolactone (PCL) scaffolds. A 100% pure Mw: 84,500 ± 1000 PCL was selected. 5 × 10 × 5 mm3 parallelepiped scaffolds were designed as a wood-pilled structure composed of 20 layers of 250 μm in height, in a non-alternate order ([0,0,0,90,90,90°]). 3D printing was made at 170 °C. Swine dental pulp stem cells (DPSCs) were extracted from lower lateral incisors of swine and cultivated until the cells reached 80% confluence. The third passage was used for seeding on the scaffolds. Phenotype of cells was determined by flow Cytometry. Live and dead, Alamar blue™, von Kossa and alizarin red staining assays were performed. Scaffolds with 290 + 30 μm strand diameter, 938 ± 80 μm pores in the axial direction and 689 ± 13 μm pores in the lateral direction were manufactured. Together, cell viability tests, von Kossa and Alizarin red staining indicate the ability of the printed scaffolds to support DPSCs attachment, proliferation and enable differentiation followed by mineralization. The selected material-processing technique-cell line (PCL-3D printing-DPSCs) triplet can be though to be used for further modelling and preclinical experiments in bone engineering studies.
For decades, jarosites have been precipitated by controlling Fe in hydrometallurgical circuits. In addition, their synthesis, characterization, precious metals incorporation, decomposition and leaching have led to important results in this field. Nowadays, new topics related to the synthesis of these compounds have directed studies for applications such as lithium-ion batteries (as cathodes or/and anodes). Additionally, in this work, the evaluation of these kinds of compounds as biomaterials to be used in bone tissue engineering is shown, which is a novel application of these jarosite type-compounds. The method used for the synthesis of these compounds has been improved, decreasing the temperature (from 95 to 70 °C) and synthesis time (from 24 to only 3 h), which allows the doping of the potassium jarosite with calcium, strontium and magnesium (JKCa, JKCa2 and JKAll). The powders obtained this way were characterized confirming the incorporation of these elements into the structure, and the biological assays allowing the cell proliferation at 10 days conclude that these compounds are viable as a biomaterial, due to their non-toxic property. On the other hand, these jarosites show osteoinduction when added to the swine dental pulp stem cells and can be used for orthodontic purpouses.
Cleft palate (CP) is one of the most common birth defects, presenting a multitude of negative impacts on the health of the patient. It also leads to increased mortality at all stages of life, economic costs and psychosocial effects. The embryological development of CP has been outlined thanks to the advances made in recent years due to biomolecular successions. The etiology is broad and combines certain environmental and genetic factors. Currently, all surgical interventions work off the principle of restoring the area of the fissure and aesthetics of the patient, making use of bone substitutes. These can involve biological products, such as a demineralized bone matrix, as well as natural–synthetic polymers, and can be supplemented with nutrients or growth factors. For this reason, the following review analyzes different biomaterials in which nutrients or biomolecules have been added to improve the bioactive properties of the tissue construct to regenerate new bone, taking into account the greatest limitations of this approach, which are its use for bone substitutes for large areas exclusively and the lack of vascularity. Bone tissue engineering is a promising field, since it favors the development of porous synthetic substitutes with the ability to promote rapid and extensive vascularization within their structures for the regeneration of the CP area.
Articular cartilage is a specialized tissue that provides a smooth surface for joint movement and load transmission. Unfortunately, it has limited regenerative capacity. Tissue engineering, combining different cell types, scaffolds, growth factors, and physical stimulation has become an alternative for repairing and regenerating articular cartilage. Dental Follicle Mesenchymal Stem Cells (DFMSCs) are attractive candidates for cartilage tissue engineering because of their ability to differentiate into chondrocytes, on the other hand, the polymers blend like Polycaprolactone (PCL) and Poly Lactic-co-Glycolic Acid (PLGA) have shown promise given their mechanical properties and biocompatibility. In this work, the physicochemical properties of polymer blends were evaluated by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) and were positive for both techniques. The DFMSCs demonstrated stemness by flow cytometry. The scaffold showed to be a non-toxic effect when we evaluated it with Alamar blue, and the samples were analyzed using SEM and phalloidin staining to evaluate cell adhesion to the scaffold. The synthesis of glycosaminoglycans was positive on the construct in vitro. Finally, the PCL/PLGA scaffold showed a better repair capacity than two commercial compounds, when tested in a chondral defect rat model. These results suggest that the PCL/PLGA (80:20) scaffold may be suitable for applications in the tissue engineering of articular hyaline cartilage.
Bone Regeneration represents a clinical need, related to bone defects such as congenital anomalies, trauma with bone loss, and/or some pathologies such as cysts or tumors This is why a polymeric biomaterial that mimics the osteogenic composition and structure represents a high potential to face this problem. The method of obtaining these materials was first to prepare a stabilized hydrogel by means of physical bonds and then to make use of the lyophilization technique to obtain the 3D porous scaffolds with temperature conditions of −58 °C and pressure of 1 Pa for 16 h. The physicochemical and bioactive properties of the scaffolds were studied. FTIR and TGA results confirm the presence of the initial components in the 3d matrix of the scaffold. The scaffolds exhibited a morphology with pore size and interconnectivity that promote good cell viability. Together, the cell viability and proliferation test, Alamar BlueTM and the differentiation test: alizarin staining, showed the ability of physically stabilized scaffolds to proliferate and differentiate swine dental pulp stem cell (DPSCs) followed by mineralization. Therefore, the Cs-PCL-PVA-HA scaffold stabilized by physical bonds has characteristics that suggest great utility for future complementary in vitro tests and in vivo studies on bone defects. Likewise, this biomaterial was enhanced with the addition of HA, providing a scaffold with osteoconductive properties necessary for good regeneration of bone tissue.
Today, regenerative osteogenesis represents a clinical need, due to the incidence of bone defects that involve groups of pathologies ranging from congenital anomalies to traumatic injuries, as well as problems presented surgically. This is why the design of a polymeric biomaterial (scaffold) of chitosan, carboxymethylcellulose, zinc oxide, and calcium carbonate with similar characteristics in terms of composition and bone structure offers high potential to help address this health problem. The technique for obtaining the scaffolds of this research was to develop a physical hydrogel to have the biofunctionality of the active groups of the polymer chains used, then make use of the lyophilization process to obtain three-dimensional (3D) porous scaffolds. The physicochemical and biological properties of the scaffolds were evaluated. The scaffolds presented morphology with pore size and interconnectivity that favor the need for cell proliferation and viability. The biocompatibility tests confirm that the designed scaffolds do not present cytotoxicity and the analyzes with alizarin red staining show calcium deposits in the materials with CaCO3 and ZnO. Osteoinduction assays to osteogenic lineage using runt-related transcription factor type 2 (RUNX2) and collagen type 1 (COL-1) antibodies allowed expression in differentiated cells. Therefore, the calcium carbonate-containing scaffolds stabilized by physical bonds have characteristics of being non-cytotoxic, bioactive, and osteoinductive, which motivate their use in future tests to evaluate their demeanor with rat models for bone engineering studies.
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