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The design of improved materials for orthopedic implants and bone tissue engineering scaffolds relies on materials mimicking the properties of bone. Calcium phosphate (Ca-PO4)-mineralized collagen fibrils arranged in a characteristic hierarchical structure constitute the building blocks of mineralized vertebrate tissues and control their biomechanical and biochemical properties. Large, flexible, acidic noncollagenous proteins (ANCPs) have been shown to influence collagen mineralization but little is known about mineralization mechanisms with the aid of small proteins. Osteocalcin (OCN) is a small, highly structured biomolecule known as a multifunctional hormone in its undercarboxylated form. Here, we examined the potential mechanism of collagen intrafibrillar mineralization in vitro mediated by OCN as a model protein. Rapid and random extrafibrillar mineralization of flakey Ca-PO4 particles was observed by transmission electron microscopy mainly on the outer surfaces of collagen fibrils of a preformed collagen scaffold in the absence of the protein. In contrast, the protein stabilized hydrated, spherical nanoclusters of Ca-PO4 on the outer surface of the fibrils, thereby retarding extrafibrillar mineralization. The nanoclusters then infiltrated the fibrils resulting in intrafibrillar mineralization with HAP crystals aligned with the fibrils. This mechanism is similar to that observed for unstructured ANCPs. Results of fibrillogenesis and immunogold labeling studies showed that OCN was associated primarily with the fibrils, consistent with ex vivo studies on mineralizing turkey tendon. The present findings contribute to expanding our understanding of collagen intrafibrillar mineralization and provide insight into design synthetic macromolecular matrices for orthopedic implants and bone regeneration.Cell-cell and cell-substrate interactions in coculture systems are very important to the context of biomaterial scaffolds for tissue engineering applications. Understanding the cellular interactions and distribution of epithelial-mesenchymal microtissues on the controllable biomaterial surfaces is useful to study the organoid applications. The aim of the present study is to investigate the effects of chitosan/poly(ε-caprolactone) (PCL)-blended biomaterials on the distribution and spheroid formation of HaCaT and Hs68 cells in a coculture system. In this study, we demonstrated that the cocultured cells gradually changed their pattern from core/shell spheroid to monolayered morphology as the PCL content increased in the blended substrates. Selleckchem CDK inhibitor This indicates that the chitosan/PCL-blended substrates are able to regulate cell-substrate and cell-cell interactions to modify the distribution of HaCaT and Hs68 cells similar to various mesenchymal-epithelial organizations in biological tissues. Moreover, we also developed a two-dimension lattice model to elaborate the dependence of cell spheroid development on complex cell-cell interactions. This information may be helpful to develop appropriate biomaterials with appropriate properties to the applications of engineered epithelial-mesenchymal organoids.Myocardial ischemia-reperfusion produces a large amount of reactive oxygen species (ROS), which damage the myocardial tissue. Therefore, localized scavenging of ROS from the myocardial tissue would reduce its damage and avoid metabolic abnormalities caused by systemic ROS. In this study, a free radical scavenging and biodegradable supramolecular peptide (ECAFF, named as ECF-5) hydrogel was designed as a culture scaffold for cardiomyocytes. The peptide hydrogel significantly preserved the migration and proliferation of cardiomyocytes and reduced their damage from oxidative stress. In addition, the hydrogel degraded during cell growth, which implies that it may avoid thrombosis of the capillaries in practical use and provide the opportunity for the cells to attach to each other and form a functional tissue. The hydrogel can be used as a 3D culture scaffold for cardiomyocyte culture and allow cardiomyocytes to grow into tissue-like cell spheres. The excellent nature of the ECF-5 hydrogel enables it to have broad applications in the biomedical field in the future.Calcium phosphate mineralizing peptides are of special importance for dental and orthopedic applications, such as caries remineralization and improved osteointegration. Uncovering the mechanism of action for such peptides is an ongoing challenge with the aim of a better fundamental understanding of biomineralization processes and developing optimized peptides for clinical use. It has recently been reported that "adjacent oppositely charged residue" motifs are found abundantly in cation binding, inorganic surface binding, or biomineralization-related proteins and may play a key role in the biomineralization events. Despite their medical importance, the role of these motifs has not yet been investigated on calcium phosphate mineral systems. To investigate this, we have designed peptides with different structural properties and different numbers of adjacent oppositely charged residues. We have evaluated their effects on in vitro calcium phosphate mineralization kinetics and mineral properties. The kinetics of thues.Engineering a regulatory phenotype in dendritic cells (DCs) is a potential approach to circumvent an immune response against self-antigens in autoimmunity or alloantigens in allograft rejection. Cell microenvironments influence the differentiation of DC precursors into either proinflammatory/immunostimulatory or tolerogenic/regulatory DCs. Biomaterial-based vehicles can be used to re-engineer cell microenvironments and re-educate the DC phenotype. This study presents the development and validation of a biomaterial-based multicomponent immunomodulatory (MI) scaffold for the purpose of promoting a tolerogenic/regulatory DC phenotype. Glutaraldehyde-crosslinked gelatin microparticles, loaded with specific immunomodulators, were embedded into a porous agarose scaffold. Using the Weibull equation and the Bayesian approach, an empirical mathematical model was derived from the release profile data of "model" molecules. The scaffold design was generated from the model to achieve distinct temporal release profiles of the loaded immunomodulator(s) granulocyte monocyte colony-stimulating factor (GM-CSF), dexamethasone (DEX), and/or peptidoglycan (PGN).
Homepage: https://www.selleckchem.com/CDK.html
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