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With the rising prevalence of bone-related injuries, it is crucial to improve treatments for fractures and defects. Tissue engineering offers a promising solution in the form of injectable hydrogel scaffolds that can sustain the release of growth factors like bone morphogenetic protein-2 (BMP-2) for bone repair. Recently, we discovered that tetra-PEG hydrogels (Tetra gels) undergo gel-gel phase separation (GGPS) at low polymer content, resulting in hydrophobicity and tissue affinity. In this work, we examined the potential of a newer class of gel, the oligo-tetra-PEG gel (Oligo gel), as a growth factor-releasing scaffold. We investigated the extent of GGPS occurring in the two gels and assessed their ability to sustain BMP-2 release and osteogenic potential in a mouse calvarial defect model. The Oligo gel underwent a greater degree of GGPS than the Tetra gel, exhibiting higher turbidity, hydrophobicity, and pore formation. The Oligo gel demonstrated sustained protein or growth factor release over a 21-day period from protein release kinetics and osteogenic cell differentiation studies. Finally, BMP-2-loaded Oligo gels achieved complete regeneration of critical-sized calvarial defects within 28 days, significantly outperforming Tetra gels. The easy formulation, injectability, and capacity for sustained release makes the Oligo gel a promising candidate therapeutic biomaterial.
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Visualizing polymer chain growth is always a hot topic for tailoring structure-function properties in polymer chemistry. However, current characterization methods are limited in their ability to differentiate the degree of polymerization in real-time without isolating the samples from the reaction vessel, let alone to detect insoluble polymers. Herein, a reliable relationship is established between polymer chain growth and fluorescence properties through polymerization induced emission. (TPE-C2)2 -Te is used to realize in situ oxidative polymerization, leading to the aggregation of fluorophores. The relationship between polymerization degree of growing polytelluoxane (PTeO) and fluorescence intensity is constructed, enabling real-time monitoring of the polymerization reaction. More importantly, this novel method can be further applied to the observation of the polymerization process for growing insoluble polymer via surface polymerization. Therefore, the development of visualization technology will open a new avenue for visualizing polymer chain growth in real-time, regardless of polymer solubility.
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Four-armed poly(ethylene glycol) (PEG)s are essential hydrophilic polymers extensively utilized to prepare PEG hydrogels, which are valuable tissue scaffolds. When hydrogels are used in vivo, they eventually dissociate due to cleavage of the backbone structure. When the cleavage occurs at the cross-linking point, the hydrogel elutes as an original polymer unit, i.e., four-armed PEG. Although four-armed PEGs have been utilized as subcutaneously implanted biomaterials, the diffusion, biodistribution, and clearance behavior of four-armed PEG from the skin are not fully understood. This paper investigates time-wise diffusion from the skin, biodistribution to distant organs, and clearance of fluorescence-labeled four-armed PEGs with molecular weight (Mw) ranging from 5-40 kg/mol subcutaneously injected into the back of mice. Changes over time indicated that the fate of subcutaneously injected PEGs is Mw-dependent. Four-armed PEGs with Mw ≤ 10 kg/mol gradually diffused to deep adipose tissue beneath the injection site and distributed dominantly to distant organs, such as the kidney. PEGs with Mw ≥ 20 kg/mol stagnated in the skin and deep adipose tissue and were mainly delivered to the heart, lung, and liver. The fundamental understanding of the Mw-dependent behavior of four-armed PEGs is beneficial for preparing biomaterials using PEGs, providing a reference in the field of tissue engineering.
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Polietilenglicoles , Polímeros , Ratones , Animales , Polietilenglicoles/química , Distribución Tisular , Peso Molecular , Hidrogeles/química , Materiales BiocompatiblesRESUMEN
A diselenide bond, as a dynamic covalent bond, is a versatile tool to construct smart interfaces, which can respond to visible light. In this work, we used microcontact printing (µCP) to construct diselenide patterns on quartz substrates. Fluorescent patterns were obtained on the modified surfaces via the visible-light-induced diselenide metathesis reaction, which allowed the patterning process to be fast, dynamically erasable, and compatible with different fluorescent molecules including rhodamine B and boron-dipyrromethene (BODIPY) used in this work. A variety of analytical methods offered comprehensive evidence for the success of the printing of diselenides here. We further printed diselenide and disulfide intersecting stripes on one single quartz substrate layer by layer and introduced rhodamine B and BODIPY to obtain a multicolored pattern simultaneously. By taking advantage of their responsiveness to different wavelengths, the composite pattern of disulfides and diselenides could be erased by two stepwise stages. The fluorescent images of the modified substrate showed a good agreement with the pattern of the poly(dimethylsiloxane) (PDMS) stamp, indicating the methodology with a potential application for information storage.
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BACKGROUND AND PURPOSE: Melatonin is a neurohormone involved in bone homeostasis. Melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin-mediated bone formation-resorption balance remains undefined. EXPERIMENTAL APPROACH: Osteoporosis models were established and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors were knocked down, the NF-κB signalling pathway and receptor activator of NF-κB ligand (RANKL) expression were investigated. Communication between bone marrow mesenchymal stem cells and osteoclasts was detected with direct-contact or indirect-contact system. KEY RESULTS: Bone loss and microstructure disorder in mice were reversed after melatonin treatment, as a result of anabolic and anti-resorptive effects. In vitro, a physiological (low) concentration of melatonin promoted the bone marrow mesenchymal stem cells, osteogenic lineage commitment and extracellular mineralization but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT2 , the positive effects of melatonin on osteogenesis were attenuated. The canonical NF-κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be down-regulated by melatonin during osteogenesis. Melatonin suppressed BMMSC-mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs and this effect only occurred when BMMSCs and osteoclast precursors were co-cultured in an indirect-contact manner. CONCLUSION AND IMPLICATIONS: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of bone marrow mesenchymal stem cells by suppressing the MT2 -dependent NF-κB signalling pathway, and down-regulates osteoclastogenesis via RANKL paracrine secretion.
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Resorción Ósea , Melatonina , Células Madre Mesenquimatosas , Animales , Células de la Médula Ósea , Diferenciación Celular , Melatonina/farmacología , Ratones , FN-kappa B , Osteoclastos , Osteogénesis , Ligando RANKRESUMEN
Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. Studies have shown that OPN plays a role in bone metabolism and homeostasis. OPN not only is an important factor in neuron-mediated and endocrine-regulated bone mass, but also is involved in biological activities such as proliferation, migration, and adhesion of several bone-related cells, including bone marrow mesenchymal stem cells, hematopoietic stem cells, osteoclasts, and osteoblasts. OPN has been demonstrated to be closely related to the occurrence and development of many bone-related diseases, such as osteoporosis, rheumatoid arthritis, and osteosarcoma. As expected, the functions of OPN in the bone have become a research hotspot. In this article, we try to decipher the mechanism of OPN-regulated bone metabolism and bone diseases.
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Enfermedades Óseas/metabolismo , Huesos/metabolismo , Osteopontina/metabolismo , Animales , Desarrollo Óseo , Huesos/patología , Calcinosis/patología , Humanos , Tamaño de los ÓrganosRESUMEN
Recently, peroxymonosulfate (PMS)-based advanced oxidation processes have exhibited broad application prospects in the environment field. Accordingly, a simple, rapid, and ultrasensitive method is highly desired for the specific recognition and accurate quantification of PMS in various aqueous solutions. In this work, SO4â¢--induced aromatic hydroxylation was explored, and based on that, for the first time, a novel fluorescence method was developed for the PMS determination using Co2+ as a PMS activator and benzoic acid (BA) as a chemical probe. Through a suite of spectral, chromatographic, and mass spectrometric analyses, SO4â¢- was proven to be the dominant radical species, and salicylic acid was identified as the fluorescent molecule. As a result, a whole radical chain reaction mechanism for the generation of salicylic acid in the BA/PMS/Co2+ system was proposed. This fluorescence method possessed a rapid reaction equilibrium (<1 min), an ultrahigh sensitivity (detection limit = 10 nM; quantification limit = 33 nM), an excellent specificity, and a wide detection range (0-100 µM). Moreover, it performed well in the presence of possible interfering substances, including two other peroxides (i.e., peroxydisulfate and hydrogen peroxide), some common ions, and organics. The detection results for real water samples further validated the practical utility of the developed fluorescence method. This work provides a new method for the specific recognition and sensitive determination of PMS in complex aqueous solutions.