Journal articles on the topic 'Protein scaffolds'
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1
Ortiz-Muñoz, Andrés, Héctor F. Medina-Abarca, and Walter Fontana. "Combinatorial protein–protein interactions on a polymerizing scaffold." Proceedings of the National Academy of Sciences 117, no. 6 (January 24, 2020): 2930–37. http://dx.doi.org/10.1073/pnas.1912745117.
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Scaffold proteins organize cellular processes by bringing signaling molecules into interaction, sometimes by forming large signalosomes. Several of these scaffolds are known to polymerize. Their assemblies should therefore not be understood as stoichiometric aggregates, but as combinatorial ensembles. We analyze the combinatorial interaction of ligands loaded on polymeric scaffolds, in both a continuum and discrete setting, and compare it with multivalent scaffolds with fixed number of binding sites. The quantity of interest is the abundance of ligand interaction possibilities—the catalytic potential Q—in a configurational mixture. Upon increasing scaffold abundance, scaffolding systems are known to first increase opportunities for ligand interaction and then to shut them down as ligands become isolated on distinct scaffolds. The polymerizing system stands out in that the dependency of Q on protomer concentration switches from being dominated by a first order to a second order term within a range determined by the polymerization affinity. This behavior boosts Q beyond that of any multivalent scaffold system. In addition, the subsequent drop-off is considerably mitigated in that Q decreases with half the power in protomer concentration than for any multivalent scaffold. We explain this behavior in terms of how the concentration profile of the polymer-length distribution adjusts to changes in protomer concentration and affinity. The discrete case turns out to be similar, but the behavior can be exaggerated at small protomer numbers because of a maximal polymer size, analogous to finite-size effects in bond percolation on a lattice.
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Bari, Elia, Franca Scocozza, Sara Perteghella, Marzio Sorlini, Ferdinando Auricchio, Maria Luisa Torre, and Michele Conti. "3D Bioprinted Scaffolds Containing Mesenchymal Stem/Stromal Lyosecretome: Next Generation Controlled Release Device for Bone Regenerative Medicine." Pharmaceutics 13, no. 4 (April 8, 2021): 515. http://dx.doi.org/10.3390/pharmaceutics13040515.
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Three-dimensional printing of poly(ε-caprolactone) (PCL) is a consolidated scaffold manufacturing technique for bone regenerative medicine. Simultaneously, the mesenchymal stem/stromal cell (MSC) secretome is osteoinductive, promoting scaffold colonization by cells, proliferation, and differentiation. The present paper combines 3D-printed PCL scaffolds with lyosecretome, a freeze-dried formulation of MSC secretome, containing proteins and extracellular vesicles (EVs). We designed a lyosecretome 3D-printed scaffold by two loading strategies: (i) MSC secretome adsorption on 3D-printed scaffold and (ii) coprinting of PCL with an alginate-based hydrogel containing MSC secretome (at two alginate concentrations, i.e., 6% or 10% w/v). A fast release of proteins and EVs (a burst of 75% after 30 min) was observed from scaffolds obtained by absorption loading, while coprinting of PCL and hydrogel, encapsulating lyosecretome, allowed a homogeneous loading of protein and EVs and a controlled slow release. For both loading modes, protein and EV release was governed by diffusion as revealed by the kinetic release study. The secretome’s diffusion is influenced by alginate, its concentration, or its cross-linking modes with protamine due to the higher steric hindrance of the polymer chains. Moreover, it is possible to further slow down protein and EV release by changing the scaffold shape from parallelepiped to cylindrical. In conclusion, it is possible to control the release kinetics of proteins and EVs by changing the composition of the alginate hydrogel, the scaffold’s shape, and hydrogel cross-linking. Such scaffold prototypes for bone regenerative medicine are now available for further testing of safety and efficacy.
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Finch, Anthony, and Jin Kim. "Thermophilic Proteins as Versatile Scaffolds for Protein Engineering." Microorganisms 6, no. 4 (September 25, 2018): 97. http://dx.doi.org/10.3390/microorganisms6040097.
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Literature from the past two decades has outlined the existence of a trade-off between protein stability and function. This trade-off creates a unique challenge for protein engineers who seek to introduce new functionality to proteins. These engineers must carefully balance the mutation-mediated creation and/or optimization of function with the destabilizing effect of those mutations. Subsequent research has shown that protein stability is positively correlated with “evolvability” or the ability to support mutations which bestow new functionality on the protein. Since the ultimate goal of protein engineering is to create and/or optimize a protein’s function, highly stable proteins are preferred as potential scaffolds for protein engineering. This review focuses on the application potential for thermophilic proteins as scaffolds for protein engineering. The relatively high inherent thermostability of these proteins grants them a great deal of mutational robustness, making them promising scaffolds for various protein engineering applications. Comparative studies on the evolvability of thermophilic and mesophilic proteins have strongly supported the argument that thermophilic proteins are more evolvable than mesophilic proteins. These findings indicate that thermophilic proteins may represent the scaffold of choice for protein engineering in the future.
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Simunovic, Mijo, Emma Evergren, Ivan Golushko, Coline Prévost, Henri-François Renard, Ludger Johannes, Harvey T. McMahon, Vladimir Lorman, Gregory A. Voth, and Patricia Bassereau. "How curvature-generating proteins build scaffolds on membrane nanotubes." Proceedings of the National Academy of Sciences 113, no. 40 (September 21, 2016): 11226–31. http://dx.doi.org/10.1073/pnas.1606943113.
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Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube’s length. Our work implies that the nature of local protein–membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30–40% of a tube’s surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes.
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Pham, Phuong Ngoc, Maroš Huličiak, Lada Biedermannová, Jiří Černý, Tatsiana Charnavets, Gustavo Fuertes, Štěpán Herynek, et al. "Protein Binder (ProBi) as a New Class of Structurally Robust Non-Antibody Protein Scaffold for Directed Evolution." Viruses 13, no. 2 (January 27, 2021): 190. http://dx.doi.org/10.3390/v13020190.
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Engineered small non-antibody protein scaffolds are a promising alternative to antibodies and are especially attractive for use in protein therapeutics and diagnostics. The advantages include smaller size and a more robust, single-domain structural framework with a defined binding surface amenable to mutation. This calls for a more systematic approach in designing new scaffolds suitable for use in one or more methods of directed evolution. We hereby describe a process based on an analysis of protein structures from the Protein Data Bank and their experimental examination. The candidate protein scaffolds were subjected to a thorough screening including computational evaluation of the mutability, and experimental determination of their expression yield in E. coli, solubility, and thermostability. In the next step, we examined several variants of the candidate scaffolds including their wild types and alanine mutants. We proved the applicability of this systematic procedure by selecting a monomeric single-domain human protein with a fold different from previously known scaffolds. The newly developed scaffold, called ProBi (Protein Binder), contains two independently mutable surface patches. We demonstrated its functionality by training it as a binder against human interleukin-10, a medically important cytokine. The procedure yielded scaffold-related variants with nanomolar affinity.
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Wang, Hong Xin, Zheng Xiang Xue, Mei Hong Wei, Deng Long Chen, and Min Li. "A Novel Scaffold from Recombinant Spider Silk Protein in Tissue Engineering." Advanced Materials Research 152-153 (October 2010): 1734–44. http://dx.doi.org/10.4028/www.scientific.net/amr.152-153.1734.
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As a new biomaterial, recombinant spider silk protein has attracted much attention in tissue engineering. The pNSR-16/ BL21(DE3)pLysS strains fermented and produced the recombinant spider silk protein, which was then cast into scaffolds. NIH-3T3 cells were cultivated with extractions of the scaffolds in vitro. The cytotoxicity of scaffolds was analyzed with a MTT assay. The performances of cells adhesion, growth and expression on the scaffolds were observed with SEM, HE staining and immunohistochemistry. Compared with the control, the extract fluid of materials culturing the NIH-3T3 cells was not apparently different. NIH-3T3 cells could adhere and grow on the scaffolds and secret FGF-2. The pNSR-16 recombinant spider silk protein scaffolds has satisfactory cytocompatibility and the scaffolds are ideal scaffold material for tissue engineering.
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Lin, Peng, Hui Yang, Eiji Nakata, and Takashi Morii. "Mechanistic Aspects for the Modulation of Enzyme Reactions on the DNA Scaffold." Molecules 27, no. 19 (September 24, 2022): 6309. http://dx.doi.org/10.3390/molecules27196309.
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Cells have developed intelligent systems to implement the complex and efficient enzyme cascade reactions via the strategies of organelles, bacterial microcompartments and enzyme complexes. The scaffolds such as the membrane or protein in the cell are believed to assist the co-localization of enzymes and enhance the enzymatic reactions. Inspired by nature, enzymes have been located on a wide variety of carriers, among which DNA scaffolds attract great interest for their programmability and addressability. Integrating these properties with the versatile DNA–protein conjugation methods enables the spatial arrangement of enzymes on the DNA scaffold with precise control over the interenzyme distance and enzyme stoichiometry. In this review, we survey the reactions of a single type of enzyme on the DNA scaffold and discuss the proposed mechanisms for the catalytic enhancement of DNA-scaffolded enzymes. We also review the current progress of enzyme cascade reactions on the DNA scaffold and discuss the factors enhancing the enzyme cascade reaction efficiency. This review highlights the mechanistic aspects for the modulation of enzymatic reactions on the DNA scaffold.
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Thanyaphoo, Suphannee, and Jasadee Kaewsrichan. "A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2." Acta Pharmaceutica 66, no. 3 (September 1, 2016): 373–85. http://dx.doi.org/10.1515/acph-2016-0026.
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Abstract Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.
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Ford, Audrey C., Hans Machula, Robert S. Kellar, and Brent A. Nelson. "Characterizing the mechanical properties of tropoelastin protein scaffolds." MRS Proceedings 1569 (2013): 45–50. http://dx.doi.org/10.1557/opl.2013.1059.
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ABSTRACTThis paper reports on mechanical characterization of electrospun tissue scaffolds formed from varying blends of collagen and human tropoelastin. The electrospun tropoelastin-based scaffolds have an open, porous structure conducive to cell attachment and have been shown to exhibit strong biocompatibility, but the mechanical character is not well known. Mechanical properties were tested for scaffolds consisting of 100% tropoelastin and 1:1 tropoelastin-collagen blends. The results showed that the materials exhibited a three order of magnitude change in the initial elastic modulus when tested dry vs. hydrated, with moduli of 21 MPa and 0.011 MPa respectively. Noncrosslinked and crosslinked tropoelastin scaffolds exhibited the same initial stiffness from 0 to 50% strain, and the noncrosslinked scaffolds exhibited no stiffness at strains >∼50%. The elastic modulus of a 1:1 tropoelastin-collagen blend was 50% higher than that of a pure tropoelastin scaffold. Finally, the 1:1 tropoelastin-collagen blend was five times stiffer from 0 to 50% strain when strained at five times the ASTM standard rate. By systematically varying protein composition and crosslinking, the results demonstrate how protein scaffolds might be manipulated as customized biomaterials, ensuring mechanical robustness and potentially improving biocompatibility through minimization of compliance mismatch with the surrounding tissue environment. Moreover, the demonstration of strain-rate dependent mechanical behavior has implications for mechanical design of tropoelastin-based tissue scaffolds.
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Chen, Cheng-Yu, Ming-You Shie, Alvin Kai-Xing Lee, Yun-Ting Chou, Chun Chiang, and Chun-Pin Lin. "3D-Printed Ginsenoside Rb1-Loaded Mesoporous Calcium Silicate/Calcium Sulfate Scaffolds for Inflammation Inhibition and Bone Regeneration." Biomedicines 9, no. 8 (July 28, 2021): 907. http://dx.doi.org/10.3390/biomedicines9080907.
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Bone defects are commonly found in the elderly and athletic population due to systemic diseases such as osteoporosis and trauma. Bone scaffolds have since been developed to enhance bone regeneration by acting as a biological extracellular scaffold for cells. The main advantage of a bone scaffold lies in its ability to provide various degrees of structural support and growth factors for cellular activities. Therefore, we designed a 3D porous scaffold that can not only provide sufficient mechanical properties but also carry drugs and promote cell viability. Ginsenoside Rb1 (GR) is an extract from panax ginseng, which has been used for bone regeneration and repair since ancient Chinese history. In this study, we fabricated scaffolds using various concentrations of GR with mesoporous calcium silicate/calcium sulfate (MSCS) and investigated the scaffold’s physical and chemical characteristic properties. PrestoBlue, F-actin staining, and ELISA were used to demonstrate the effect of the GR-contained MSCS scaffold on cell proliferation, morphology, and expression of the specific osteogenic-related protein of human dental pulp stem cells (hDPSCs). According to our data, hDPSCs cultivated in GR-contained MSCS scaffold had preferable abilities of proliferation and higher expression of the osteogenic-related protein and could effectively inhibit inflammation. Finally, in vivo performance was assessed using histological results that revealed the GR-contained MSCS scaffolds were able to further achieve more effective hard tissue regeneration than has been the case in the past. Taken together, this study demonstrated that a GR-containing MSCS 3D scaffold could be used as a potential alternative for future bone tissue engineering studies and has good potential for clinical use.
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Finoli, Anthony, Eva Schmelzer, Patrick Over, Ian Nettleship, and Joerg C. Gerlach. "Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells." BioMed Research International 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/6040146.
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Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.
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Tanase, Constantin Edi, Omar Qutachi, Lisa J. White, Kevin M. Shakesheff, Andrew W. McCaskie, Serena M. Best, and Ruth E. Cameron. "Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds." Regenerative Biomaterials 6, no. 5 (April 22, 2019): 279–87. http://dx.doi.org/10.1093/rb/rbz015.
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Abstract Tissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen.
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Voisin-Chiret, Anne Sophie, and Sylvain Rault. "Using halo (het) arylboronic species to achieve synthesis of foldamers as protein–protein interaction disruptors." Pure and Applied Chemistry 84, no. 11 (June 5, 2012): 2467–78. http://dx.doi.org/10.1351/pac-con-11-10-30.
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Protein–protein interactions (PPIs) play a central role in all biological processes and have been the focus of intense investigations from structural molecular biology to cell biology for the majority of the last two decades and, more recently, are emerging as important targets for pharmaceuticals. A common motif found at the interface of PPIs is the α-helix, and apart from the peptidic structures, numerous nonpeptidic small molecules have been developed to mimic α-helices. The first-generation terphenyl scaffold is able to successfully mimic key helix residues and disrupt relevant interactions, including Bcl-xL-Bak interactions that are implicated in apoptosis mechanism. These scaffolds were designed and evaluated in silico. Analysis revealed that substituents on aromatic scaffolds can efficiently mimic side-chain surfaces. Unfortunately, the literature describes a long and difficult procedure to access these aromatic-based scaffolds. The search for new simpler methodology is the aim of the research of our medicinal chemistry team. On the basis of structural requirements, we developed a program concerning the synthesis of new oligo(het)aryl scaffolds produced by iterative couplings of boronic species (garlanding) in which substituents on rings project functionality in spatial orientations that mimic residues of an α-helix.
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Ngo, Tien Anh, Huyen Dinh, Thang Minh Nguyen, Fong Fong Liew, Eiji Nakata, and Takashi Morii. "Protein adaptors assemble functional proteins on DNA scaffolds." Chemical Communications 55, no. 83 (2019): 12428–46. http://dx.doi.org/10.1039/c9cc04661e.
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The methods applied for assembling proteins of interest on DNA scaffolds were categorized and the recent advance of DNA-binding adaptor mediated assembly of proteins on the DNA scaffolds is discussed.
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Luo, En, Jun Cui, Y. Gao, Yun Feng Lin, S. S. Zhu, and J. Hu. "Effect of Pamidronate on Protein Adsorption and Osteoblast Adhesion to Hydroxyapatite Bioceramics Scaffold." Key Engineering Materials 330-332 (February 2007): 885–88. http://dx.doi.org/10.4028/www.scientific.net/kem.330-332.885.
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This study is to investigate the effect of PAM on protein adsorption and osteoblastic cells adhesion to HA bioceramics. PAM was immobilized on the surface of HA bioceramics for bone scaffold by chelating. The outermost layer of the specimens was analyzed by XPS and FT-IR. The protein adsorption test was performed using the 10% bovine calf serum absorbed on the specimens in vitro. The osteoblastic cells were inoculated and cultured on the scaffolds. SEM, MTT test and ALP activity test evaluated the cell attachment, proliferation and activity on the scaffolds. Characteristic peaks in XPS and FT-IR spectra indicated PAM being immobilized on the surface of the bioceramics. PAGE and 2-D DIGE results indicated that HA absorbed more acidic proteins, while PAM-HA absorbed more basic and neutral proteins.The cell culture test indicated that the cells actively proliferated on the scaffolds. There was no significant difference between the ALP activity of the cells cultured for 1d, 3d, 5d and 7d on PAM-HA and that of the controls. PAM had no obvious effect on the cytocompatibility of HA, and PAM-HA bioceramics could be used as bone scaffold with potential ability to improve osteogenesis.
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Li, Ji-Xin, Shu-Xiang Zhao, and Yu-Qing Zhang. "Silk Protein Composite Bioinks and Their 3D Scaffolds and In Vitro Characterization." International Journal of Molecular Sciences 23, no. 2 (January 14, 2022): 910. http://dx.doi.org/10.3390/ijms23020910.
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This paper describes the use of silk protein, including fibroin and sericin, from an alkaline solution of Ca(OH)2 for the clean degumming of silk, which is neutralized by sulfuric acid to create calcium salt precipitation. The whole sericin (WS) can not only be recycled, but completely degummed silk fibroin (SF) is also obtained in this process. The inner layers of sericin (ILS) were also prepared from the degummed silk in boiling water by 120 °C water treatment. When the three silk proteins (SPs) were individually grafted with glycidyl methacrylate (GMA), three grafted silk proteins (G-SF, G-WS, G-ILS) were obtained. After adding I2959 (a photoinitiator), the SP bioinks were prepared with phosphate buffer (PBS) and subsequently bioprinted into various SP scaffolds with a 3D network structure. The compressive strength of the SF/ILS (20%) scaffold added to G-ILS was 45% higher than that of the SF scaffold alone. The thermal decomposition temperatures of the SF/WS (10%) and SF/ILS (20%) scaffolds, mainly composed of a β-sheet structures, were 3 °C and 2 °C higher than that of the SF scaffold alone, respectively. The swelling properties and resistance to protease hydrolysis of the SP scaffolds containing sericin were improved. The bovine insulin release rates reached 61% and 56% after 5 days. The L929 cells adhered, stretched, and proliferated well on the SP composite scaffold. Thus, the SP bioinks obtained could be used to print different types of SP composite scaffolds adapted to a variety of applications, including cells, drugs, tissues, etc. The techniques described here provide potential new applications for the recycling and utilization of sericin, which is a waste product of silk processing.
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Bai, Yushi, Zanlin Yu, Larry Ackerman, Yan Zhang, Johan Bonde, Wu Li, Yifan Cheng, and Stefan Habelitz. "Protein nanoribbons template enamel mineralization." Proceedings of the National Academy of Sciences 117, no. 32 (July 31, 2020): 19201–8. http://dx.doi.org/10.1073/pnas.2007838117.
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As the hardest tissue formed by vertebrates, enamel represents nature’s engineering masterpiece with complex organizations of fibrous apatite crystals at the nanometer scale. Supramolecular assemblies of enamel matrix proteins (EMPs) play a key role as the structural scaffolds for regulating mineral morphology during enamel development. However, to achieve maximum tissue hardness, most organic content in enamel is digested and removed at the maturation stage, and thus knowledge of a structural protein template that could guide enamel mineralization is limited at this date. Herein, by examining a gene-modified mouse that lacked enzymatic degradation of EMPs, we demonstrate the presence of protein nanoribbons as the structural scaffolds in developing enamel matrix. Using in vitro mineralization assays we showed that both recombinant and enamel-tissue–based amelogenin nanoribbons are capable of guiding fibrous apatite nanocrystal formation. In accordance with our understanding of the natural process of enamel formation, templated crystal growth was achieved by interaction of amelogenin scaffolds with acidic macromolecules that facilitate the formation of an amorphous calcium phosphate precursor which gradually transforms into oriented apatite fibers along the protein nanoribbons. Furthermore, this study elucidated that matrix metalloproteinase-20 is a critical regulator of the enamel mineralization as only a recombinant analog of a MMP20-cleavage product of amelogenin was capable of guiding apatite mineralization. This study highlights that supramolecular assembly of the scaffold protein, its enzymatic processing, and its ability to interact with acidic carrier proteins are critical steps for proper enamel development.
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Napavichayanun, Supamas, Prompong Pienpinijtham, Narendra Reddy, and Pornanong Aramwit. "Superior Technique for the Production of Agarose Dressing Containing Sericin and Its Wound Healing Property." Polymers 13, no. 19 (September 30, 2021): 3370. http://dx.doi.org/10.3390/polym13193370.
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Finding a simple and eco-friendly production technique that matches to the natural agent and results in a truly valuable natural scaffold production is still limited amongst the intensively competitive natural scaffold development. Therefore, the purpose of this study was to develop natural scaffolds that were environmentally friendly, low cost, and easily produced, using natural agents and a physical crosslinking technique. These scaffolds were prepared from agarose and sericin using the freeze-drying method (D) or freeze-thawing together with the freeze-drying method (TD). Moreover, plasticizers were added into the scaffold to improve their properties. Their physical, mechanical, and biological properties were investigated. The results showed that scaffolds that were prepared using the TD method had stronger bonding between sericin and other compounds, leading to a low swelling ratio and low protein release of the scaffolds. This property may be applied in the development of further material as a controlled drug release scaffold. Adding plasticizers, especially glycerin, into the scaffolds significantly increased elongation properties, leading to an increase in elasticity of the scaffold. Moreover, all scaffolds could activate cell migration, which had an advantage on wound healing acceleration. Accordingly, this study was successful in developing natural scaffolds using natural agents and simple and green crosslinking methods.
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Smaldone, Giovanni, Alessia Ruggiero, Nicole Balasco, and Luigi Vitagliano. "Development of a Protein Scaffold for Arginine Sensing Generated through the Dissection of the Arginine-Binding Protein from Thermotoga maritima." International Journal of Molecular Sciences 21, no. 20 (October 12, 2020): 7503. http://dx.doi.org/10.3390/ijms21207503.
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Arginine is one of the most important nutrients of living organisms as it plays a major role in important biological pathways. However, the accumulation of arginine as consequence of metabolic defects causes hyperargininemia, an autosomal recessive disorder. Therefore, the efficient detection of the arginine is a field of relevant biomedical/biotechnological interest. Here, we developed protein variants suitable for arginine sensing by mutating and dissecting the multimeric and multidomain structure of Thermotoga maritima arginine-binding protein (TmArgBP). Indeed, previous studies have shown that TmArgBP domain-swapped structure can be manipulated to generate simplified monomeric and single domain scaffolds. On both these stable scaffolds, to measure tryptophan fluorescence variations associated with the arginine binding, a Phe residue of the ligand binding pocket was mutated to Trp. Upon arginine binding, both mutants displayed a clear variation of the Trp fluorescence. Notably, the single domain scaffold variant exhibited a good affinity (~3 µM) for the ligand. Moreover, the arginine binding to this variant could be easily reverted under very mild conditions. Atomic-level data on the recognition process between the scaffold and the arginine were obtained through the determination of the crystal structure of the adduct. Collectively, present data indicate that TmArgBP scaffolds represent promising candidates for developing arginine biosensors.
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Sah, Mahesh Kumar, Indranil Banerjee, and Krishna Pramanik. "Eggshell Membrane Protein Modified Silk Fibroin-Poly Vinyl Alcohol Scaffold for Bone Tissue Engineering: In Vitro and In Vivo Study." Journal of Biomimetics, Biomaterials and Biomedical Engineering 32 (May 2017): 69–81. http://dx.doi.org/10.4028/www.scientific.net/jbbbe.32.69.
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There is a need for high performance scaffold in tissue engineering. Keeping this perspective in mind, the present study delineates the preparation and physico-chemical characterization of soluble eggshell protein (SEP) modified silk fibroin (SF)-polyvinyl alcohol (PVA) scaffold and its application in bone tissue engineering. The SF/PVA scaffold were prepared by salt leaching and modified with eggshell protein. Micro-architechture and porosity analysis revealed that all the scaffolds were having desired pore size (230-360 µm), interconnected porous network and 90% porosity. The scaffolds were found with suitable swelling behavior and biodegradability to support cell proliferation till replaces native osseous tissue. In vitro cyto-compatibility and differentiation study showed that SEP(SF-PVA) supports viability , proliferation and differentiation of cord blood derived human mesenchymal stem cell. Further, in vivo study in mice model showed that the scaffolds are non-immunogenic and support tissue growth. In conclusion, SEP modified SF-PVA scaffold could be a better option for tissue engineering.
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Caldwell, Shane J., Ian C. Haydon, Nikoletta Piperidou, Po-Ssu Huang, Matthew J. Bick, H. Sebastian Sjöström, Donald Hilvert, David Baker, and Cathleen Zeymer. "Tight and specific lanthanide binding in a de novo TIM barrel with a large internal cavity designed by symmetric domain fusion." Proceedings of the National Academy of Sciences 117, no. 48 (November 17, 2020): 30362–69. http://dx.doi.org/10.1073/pnas.2008535117.
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De novo protein design has succeeded in generating a large variety of globular proteins, but the construction of protein scaffolds with cavities that could accommodate large signaling molecules, cofactors, and substrates remains an outstanding challenge. The long, often flexible loops that form such cavities in many natural proteins are difficult to precisely program and thus challenging for computational protein design. Here we describe an alternative approach to this problem. We fused two stable proteins with C2 symmetry—a de novo designed dimeric ferredoxin fold and a de novo designed TIM barrel—such that their symmetry axes are aligned to create scaffolds with large cavities that can serve as binding pockets or enzymatic reaction chambers. The crystal structures of two such designs confirm the presence of a 420 cubic Ångström chamber defined by the top of the designed TIM barrel and the bottom of the ferredoxin dimer. We functionalized the scaffold by installing a metal-binding site consisting of four glutamate residues close to the symmetry axis. The protein binds lanthanide ions with very high affinity as demonstrated by tryptophan-enhanced terbium luminescence. This approach can be extended to other metals and cofactors, making this scaffold a modular platform for the design of binding proteins and biocatalysts.
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Hershberger, Stefan, Song-Gil Lee, and Jean Chmielewski. "Scaffolds for Blocking Protein-Protein Interactions." Current Topics in Medicinal Chemistry 7, no. 10 (May 1, 2007): 928–42. http://dx.doi.org/10.2174/156802607780906726.
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Jenkins, Timothy, Thomas Fryer, Rasmus Dehli, Jonas Jürgensen, Albert Fuglsang-Madsen, Sofie Føns, and Andreas Laustsen. "Toxin Neutralization Using Alternative Binding Proteins." Toxins 11, no. 1 (January 17, 2019): 53. http://dx.doi.org/10.3390/toxins11010053.
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Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and mortality among snakebite victims, current antivenoms suffer from several drawbacks, such as immunogenicity and high cost of production. Consequently, avenues for improving envenoming therapy, such as the discovery of toxin-sequestering monoclonal antibodies against medically important target toxins through phage display selection, are being explored. However, alternative binding protein scaffolds that exhibit certain advantages compared to the well-known immunoglobulin G scaffold, including high stability under harsh conditions and low cost of production, may pose as possible low-cost alternatives to antibody-based therapeutics. There is now a plethora of alternative binding protein scaffolds, ranging from antibody derivatives (e.g., nanobodies), through rationally designed derivatives of other human proteins (e.g., DARPins), to derivatives of non-human proteins (e.g., affibodies), all exhibiting different biochemical and pharmacokinetic profiles. Undeniably, the high level of engineerability and potentially low cost of production, associated with many alternative protein scaffolds, present an exciting possibility for the future of snakebite therapeutics and merit thorough investigation. In this review, a comprehensive overview of the different types of binding protein scaffolds is provided together with a discussion on their relevance as potential modalities for use as next-generation antivenoms.
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Ronca, Alfredo, Vincenzo Guarino, Maria Grazia Raucci, Francesca Salamanna, Lucia Martini, Stefania Zeppetelli, Milena Fini, et al. "Large defect-tailored composite scaffolds for in vivo bone regeneration." Journal of Biomaterials Applications 29, no. 5 (June 20, 2014): 715–27. http://dx.doi.org/10.1177/0885328214539823.
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The discovery of new strategies to repair large segmental bone defects is currently an open challenge for worldwide clinicians. In the treatment of critical-sized bone defects, an alternative strategy to traditional bone grafting is always more frequently the use of tailor-made scaffolds modelled on the final size and shape of the implant site. Here, poly-ε-caprolactone-based composite scaffolds including poly-l-lactic acid continuous fibres and hyaluronan derivates (i.e. HYAFF11®) have been investigated for the peculiar 3D architecture characterized by interconnected macroporous networks and tunable mechanical properties. Composite scaffolds were immersed in simulated body fluid solution in order to support in vivo tissue in-growth. Scaffolds loaded with autologous cells (bone marrow stromal cells) plus platelet-rich plasma and osteoconductive protein such bone morphogenetic protein-7 were also tested to evaluate eventual enhancement in bone regeneration. The morphological and mechanical properties of poly-l-lactic acid-reinforced composite scaffolds have been studied to identify the optimal scaffold design to match the implant-site requirements of sheep metatarsal defects. Dynamic mechanical tests allowed to underline the viscoelastic response of the scaffold – resulting in elastic moduli from 2.5 to 1.3 MPa, suitable to temporarily support the structural function of damaged bone tissue. In vivo preliminary investigations in a sheep model of metatarsus shaft defect also showed the attitude of the scaffold to promote osteogenesis, preferentially in association with bone marrow stromal cell and platelet-rich plasma, even if the highest amount of mature bone was reached in the case of scaffold loaded with human bone morphogenetic protein-7 released via hydrolytic degradation of HYAFF11® phases in the implant site.
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Alipour, Mahdieh, Zahra Aghazadeh, Mehdi Hassanpour, Marjan Ghorbani, Roya Salehi, and Marziyeh Aghazadeh. "MTA-Enriched Polymeric Scaffolds Enhanced the Expression of Angiogenic Markers in Human Dental Pulp Stem Cells." Stem Cells International 2022 (February 21, 2022): 1–9. http://dx.doi.org/10.1155/2022/7583489.
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Revascularization of the pulp tissue is one of the fundamental processes and challenges in regenerative endodontic procedures (REPs). In this regard, the current study is aimed at synthesizing the mineral trioxide aggregate- (MTA-) based scaffolds as a biomaterial for REPs. Poly (ε-caprolactone) (PCL)/chitosan (CS)/MTA scaffolds were constructed and evaluated by FTIR, SEM, XRD, and TGA analyses. Proliferation and adhesion of human dental pulp stem cells (hDPSCs) were assessed on these scaffolds by scanning electron microscopy (SEM) and MTT assays, respectively. The expression of angiogenic markers was investigated in gene and protein levels by real-time PCR and western blotting tests. Our results indicated that the obtained appropriate physicochemical characteristics of scaffolds could be suitable for REPs. The adhesion and proliferation level of hDPSCs were significantly increased after seeding on PCL/CS/MTA scaffolds. The expression levels of VEGFR-2, Tie2, and Angiopoietin-1 genes were statistically increased on the PCL/CS/MTA scaffold. In support of these findings, western blotting results showed the upregulation of these markers at protein levels in PCL/CS/MTA scaffold ( P < 0.05 ). The current study results suggested that PCL/CS/MTA scaffolds provide appropriate structures for the adhesion and proliferation of hDPSCs besides induction of the angiogenesis process in these cells.
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Stura, Enrico A., Michael J. Taussig, Brian J. Sutton, Stéphane Duquerroy, Stéphane Bressanelli, Anthony C. Minson, and Felix A. Rey. "Scaffolds for protein crystallisation." Acta Crystallographica Section D Biological Crystallography 58, no. 10 (September 26, 2002): 1715–21. http://dx.doi.org/10.1107/s0907444902012829.
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LEE, K., R. ITHARAJU, and D. PULEO. "Protein-imprinted polysiloxane scaffolds." Acta Biomaterialia 3, no. 4 (July 2007): 515–22. http://dx.doi.org/10.1016/j.actbio.2007.01.003.
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Lim, S. S., H. M. Zu, and H. S. Loh. "Chitosan-TiO2 nanotubes scaffolds for proliferation and early differentiation of MG63 by functionalization with fetal bovine serum." IOP Conference Series: Materials Science and Engineering 1195, no. 1 (October 1, 2021): 012041. http://dx.doi.org/10.1088/1757-899x/1195/1/012041.
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Abstract Scaffolds have been used as alternative biomaterials to overcome physiological bone disorders. Production of scaffolds has been challenging to fulfil the following criteria: biodegradability, mechanical sustainability, and biocompatibility. For cellular interaction, protein adsorbed on scaffold surface is important for osteoblastic activities. This study aimed to functionalize chitosan-TiO2 nanotubes scaffolds with fetal bovine serum and investigate in vitro efficacy of such scaffolds with fetal bovine serum. Chitosan-TiO2 nanotubes scaffolds were prepared via direct blending and lyophilization. They were then functionalized with fetal bovine serum via adsorption for 4, 8, 12 and 24 h. The in vitro efficacy of the functionalized scaffolds was evaluated using MG63 cells. The adsorption of fetal bovine serum onto the scaffolds was complex where saturation of adsorption was hardly attained. The in vitro efficacy of scaffolds with adsorbed fetal bovine serum was higher than that of those without fetal bovine serum by promoting better osteoblastic functions. Notably, the scaffolds functionalized for 4 h enhanced cell adhesion and proliferation on 7 day suggesting good regulation of osteoblastic binding and proliferation. ALP protein was expressed on 26 day in all functionalized scaffolds. Chitosan-TiO2 nanotubes scaffolds with adsorbed fetal bovine serum can be a potential regenerative material for bone regeneration.
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Danesi, Alexander L., Dimitra Athanasiadou, Ahmad Mansouri, Alina Phen, Mehrnoosh Neshatian, James Holcroft, Johan Bonde, Bernhard Ganss, and Karina M. M. Carneiro. "Uniaxial Hydroxyapatite Growth on a Self-Assembled Protein Scaffold." International Journal of Molecular Sciences 22, no. 22 (November 15, 2021): 12343. http://dx.doi.org/10.3390/ijms222212343.
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Biomineralization is a crucial process whereby organisms produce mineralized tissues such as teeth for mastication, bones for support, and shells for protection. Mineralized tissues are composed of hierarchically organized hydroxyapatite crystals, with a limited capacity to regenerate when demineralized or damaged past a critical size. Thus, the development of protein-based materials that act as artificial scaffolds to guide hydroxyapatite growth is an attractive goal both for the design of ordered nanomaterials and for tissue regeneration. In particular, amelogenin, which is the main protein that scaffolds the hierarchical organization of hydroxyapatite crystals in enamel, amelogenin recombinamers, and amelogenin-derived peptide scaffolds have all been investigated for in vitro mineral growth. Here, we describe uniaxial hydroxyapatite growth on a nanoengineered amelogenin scaffold in combination with amelotin, a mineral promoting protein present during enamel formation. This bio-inspired approach for hydroxyapatite growth may inform the molecular mechanism of hydroxyapatite formation in vitro as well as possible mechanisms at play during mineralized tissue formation.
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Wang, Xiaomei, Wanjun Chen, Zhe Chen, Yixiu Li, Kai Wu, and Yulin Song. "Preparation of 3D Printing PLGA Scaffold with BMP-9 and P-15 Peptide Hydrogel and Its Application in the Treatment of Bone Defects in Rabbits." Contrast Media & Molecular Imaging 2022 (July 31, 2022): 1–8. http://dx.doi.org/10.1155/2022/1081957.
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Objective. To prepare a three-dimensional (3D) printing polylactic acid glycolic acid (PLGA) scaffold with bone morphogenetic protein-9 (BMP-9) and P-15 peptide hydrogel and evaluate its application in treating bone defects in rabbits. Methods. 3D printing PLGA scaffolds were formed and scanned by electron microscopy. Their X-ray diffraction (XRD), in vitro degradation, and compressive strength were characterized. BMP-9 and P-15 hydrogels were prepared. Flow cytometry was used to detect apoptosis, and an electron microscope was used to evaluate cell adhesion to scaffolds. Alkaline phosphatase (ALP), type 1 collagen (Col-I), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and osterix (SP7) were detected by western blotting. MicroCT was used to detect new bone formation, and bone tissue-related protein expressions were determined in the rabbit model with bone defects. Results. The 3D printing scaffolds were cylindrical, and the inner diameter of the scaffolds was about 1 mm. The bread peak with wide distribution showed that the 3D printing only involved a physical change, which did not change the properties of the materials. The degradation rate of scaffolds was 9.38%, which met the requirements of properties of biological scaffolds. The water absorption of the support was about 9.09%, and the compressive strength was 15.83 N/mm2. In the coculture of bone marrow mesenchymal stem cells (BMSCs) with scaffolds, the 2% polypeptide hydrogel showed the most obvious activity in promoting the differentiation of BMSCs. Flow cytometry showed that the 0% and 2% groups did not cause obvious apoptosis compared with the control group. Scaffolds with 2% and 4% polypeptide promoted the expression of ALP, COL-1, OCN, RUNX2, and Sp7 in BMSCs. In vivo experiments showed that the expression of ALP, COL-1, OCN, RUNX2, and Sp7 protein in the 2% polypeptide scaffold group increased significantly compared with the model group. MicroCT detection demonstrated that the 2% polypeptide scaffold had good bone repair ability. Conclusion. The PLGA scaffolds combined with BMP-9 and P-15 peptide hydrogels had good biological and mechanical properties and could repair bone defects in rabbits.
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Lainšček, Duško, Tina Fink, Vida Forstnerič, Iva Hafner-Bratkovič, Sara Orehek, Žiga Strmšek, Mateja Manček-Keber, et al. "A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response." Vaccines 9, no. 5 (April 27, 2021): 431. http://dx.doi.org/10.3390/vaccines9050431.
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The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design.
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Zhang, Yan Hong, Liang Jun Zhu, and Ju Ming Yao. "Studies on Recombinant Human Bone Morphogenetic Protein 2 Loaded Nano-Hydroxyapatite/Silk Fibroin Scaffolds." Advanced Materials Research 175-176 (January 2011): 253–57. http://dx.doi.org/10.4028/www.scientific.net/amr.175-176.253.
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Bone Morphogenetic Protein 2 (BMP-2) is a member of the transforming growth factor superfamily. It plays an important role in stimulating osteoblast differentiation and bone formation, and has been widely utilized in clinical bone repairing by implantation. In this study, the nano-hydroxyapatite (nHA)/silk fibroin (SF) porous scaffolds were fabricated for the sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2), and then used to address the hypothesis that rhBMP-2 delivered from the scaffolds could enhance the bone formation in vitro. We optimized an effective method using a prokaryotic expression system to produce rhBMP-2. The rhBMP-2 was expressed, purified and renatured in vitro. And then the rhBMP-2 was loaded onto the nHA/SF scaffolds. The bioactivities of rhBMP-2-loaded nHA/SF scaffolds were assessed in vitro. The results showed that the rhBMP-2 promoted the osteoblasts adhesion and proliferation on the nHA/SF scaffolds. Also, the rhBMP-2 released from the nHA/SF scaffold stimulated a significant increase in alkaline phosphatase (ALP) activity of osteoblasts in vitro. These results demonstrated that the rhBMP-2-loaded nHA/SF scaffolds could promote the bone regeneration and showed potential applications in the bone tissue engineering.
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Neri, Luca M., Beat M. Riederer, Richard A. Marugg, S. Capitani, and Alberto M. Martelli. "Nuclear Scaffold Proteins Are Differently Sensitive to Stabilizing Treatment by Heat or Cu++." Journal of Histochemistry & Cytochemistry 45, no. 2 (February 1997): 295–305. http://dx.doi.org/10.1177/002215549704500214.
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The distribution of three nuclear scaffold proteins (of which one is a component of a particular class of nuclear bodies) has been studied in intact K562 human erythroleukemia cells, isolated nuclei, and nuclear scaffolds. Nuclear scaffolds were obtained by extraction with the ionic detergent lithium diidosalicylate (LIS), using nuclei prepared in the absence of divalent cations (metal-depleted nuclei) and stabilized either by a brief heat exposure (20 min at 37C or 42C) or by Cu++ ions at 0C. Proteins were visualized by in situ immunocytochemistry and confocal microscopy. Only a 160-kD nuclear scaffold protein was unaffected by all the stabilization procedures performed on isolated nuclei. However, LIS extraction and scaffold preparation procedures markedly modified the distribution of the polypeptide seen in intact cells, unless stabilization had been performed by Cu++. In isolated nuclei, only Cu++ treatment preserved the original distribution of the two other antigens (Mr 125 and 126 kD), whereas in heat-stabilized nuclei we detected dramatic changes. In nuclear scaffolds reacted with antibodies to 125- and 126-kD proteins, the fluorescent pattern was always disarranged regardless of the stabilization procedure. These results, obtained with nuclei prepared in the absence of Mg++ ions, indicate that heat treatment per se can induce changes in the distribution of nuclear proteins, at variance with previous suggestions. Nevertheless, each of the proteins we have studied behaves in a different way, possibly because of its specific association with the nuclear scaffold.
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Rojas-Yañez, Miguel-Angel, Claudia-Alejandra Rodríguez-González, Santos-Adriana Martel-Estrada, Laura-Elizabeth Valencia-Gómez, Claudia-Lucia Vargas-Requena, Juan-Francisco Hernández-Paz, María-Concepción Chavarría-Gaytán, and Imelda Olivas-Armendáriz. "Composite scaffolds of chitosan/polycaprolactone functionalized with protein of <i>Mytilus californiensis</i> for bone tissue regeneration." AIMS Materials Science 9, no. 3 (2022): 344–58. http://dx.doi.org/10.3934/matersci.2022021.
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<abstract> <p>Nowadays, the treatment for bone damage remains a significant challenge. As a result, the development of bioactive three-dimensional scaffolds for bone regeneration has become a key area of study within tissue engineering. This research is focused on the evaluation of the properties of Chitosan (Ch)/Polycaprolactone (PCL) scaffolds with the <italic>Mytilus californiensis</italic> protein by Thermally Induced Phase Separation (TIPS). This study used the extrapalleal fluid protein from <italic>Mytilus californiensis</italic> because it increases biological processes that support bone regeneration. Two methodologies were used for the scaffolds functionalization: (I) an immersion process in a solution with the protein and (II) the protein direct addition during the scaffold synthesis. The scaffolds were analyzed by Fourier Transformed Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and Mechanical Compression test to determine the composition, morphology, and mechanical properties of each material. <italic>In vitro</italic> analysis of biodegradation, bioactivity, and biocompatibility were also performed. The scaffolds with the protein added directly presented superior properties in the tests of bioactivity and cellular proliferation, making these composites attractive for the area of bone regeneration.</p> </abstract>
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Sheehy, Eamon J., Mark Lemoine, Declan Clarke, Arlyng Gonzalez Vazquez, and Fergal J. O’Brien. "The Incorporation of Marine Coral Microparticles into Collagen-Based Scaffolds Promotes Osteogenesis of Human Mesenchymal Stromal Cells via Calcium Ion Signalling." Marine Drugs 18, no. 2 (January 23, 2020): 74. http://dx.doi.org/10.3390/md18020074.
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Composite biomaterial scaffolds consisting of natural polymers and bioceramics may offer an alternative to autologous grafts for applications such as bone repair. Herein, we sought to investigate the possibility of incorporating marine coral microparticles into a collagen-based scaffold, a process which we hypothesised would enhance the mechanical properties of the scaffold as well its capacity to promote osteogenesis of human mesenchymal stromal cells. Cryomilling and sieving were utilised to achieve coral microparticles of mean diameters 14 µm and 64 µm which were separately incorporated into collagen-based slurries and freeze-dried to form porous scaffolds. X-ray diffraction and Fourier transform infrared spectroscopy determined the coral microparticles to be comprised of calcium carbonate whereas collagen/coral composite scaffolds were shown to have a crystalline calcium ethanoate structure. Crosslinked collagen/coral scaffolds demonstrated enhanced compressive properties when compared to collagen only scaffolds and also promoted more robust osteogenic differentiation of mesenchymal stromal cells, as indicated by increased expression of bone morphogenetic protein 2 at the gene level, and enhanced alkaline phosphatase activity and calcium accumulation at the protein level. Only subtle differences were observed when comparing the effect of coral microparticles of different sizes, with improved osteogenesis occurring as a result of calcium ion signalling delivered from collagen/coral composite scaffolds. These scaffolds, fabricated from entirely natural sources, therefore show promise as novel biomaterials for tissue engineering applications such as bone regeneration.
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Shuai, Ya Jun, Pan Hui, Wen He, Si Jia Min, Liang Jun Zhu, and Ming Ying Yang. "Extraction of Silk Protein from Middle Silk Gland of B.mori for Preparation of 3-D Scaffold." Advanced Materials Research 550-553 (July 2012): 1729–36. http://dx.doi.org/10.4028/www.scientific.net/amr.550-553.1729.
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In this paper, 3-D scaffolds were prepared using native protein solution extracted from middle silk gland of B.mori silkworm (SS). The distribution of pore in 3-D scaffold was homogeneous, and the pore size decreased with increase in the concentration of SS. By changing the concentration from 1.7%, 3.5% to 7%, the porosity rate of scaffolds was 95%, 94% and 91%, respectively. The water absorbency apparently decreases and the water retention rate increases with increase in the concentration of SS. The scaffolds prepared from SS with concentration of 3.5% and 7% have higher strength, on the contrary, the scaffolds prepared from SS with low concentration 1.7% shows higher elasticity. FTIR spectra indicated that SS mainly adopted β-sheet conformation. This paper proposed one green way to extract silk protein from the silk gland of B.mori silkworm and prepare its corresponding scaffolds. It seems meaning to provide implication to develop silk-based biomaterials.
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Häussling, Victor, Sebastian Deninger, Laura Vidoni, Helen Rinderknecht, Marc Ruoß, Christian Arnscheidt, Kiriaki Athanasopulu, Ralf Kemkemer, Andreas K. Nussler, and Sabrina Ehnert. "Impact of Four Protein Additives in Cryogels on Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells." Bioengineering 6, no. 3 (August 7, 2019): 67. http://dx.doi.org/10.3390/bioengineering6030067.
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Human adipose-derived mesenchymal stem/stromal cells (Ad-MSCs) have great potential for bone tissue engineering. Cryogels, mimicking the three-dimensional structure of spongy bone, represent ideal carriers for these cells. We developed poly(2-hydroxyethyl methacrylate) cryogels, containing hydroxyapatite to mimic inorganic bone matrix. Cryogels were additionally supplemented with different types of proteins, namely collagen (Coll), platelet-rich plasma (PRP), immune cells-conditioned medium (CM), and RGD peptides (RGD). The different protein components did not affect scaffolds’ porosity or water-uptake capacity, but altered pore size and stiffness. Stiffness was highest in scaffolds with PRP (82.3 kPa), followed by Coll (55.3 kPa), CM (45.6 kPa), and RGD (32.8 kPa). Scaffolds with PRP, CM, and Coll had the largest pore diameters (~60 µm). Ad-MSCs were osteogenically differentiated on these scaffolds for 14 days. Cell attachment and survival rates were comparable for all four scaffolds. Runx2 and osteocalcin levels only increased in Ad-MSCs on Coll, PRP and CM cryogels. Osterix levels increased slightly in Ad-MSCs differentiated on Coll and PRP cryogels. With differentiation alkaline phosphatase activity decreased under all four conditions. In summary, besides Coll cryogel our PRP cryogel constitutes as an especially suitable carrier for bone tissue engineering. This is of special interest, as this scaffold can be generated with patients’ PRP.
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Muzio, Giuliana, Germana Martinasso, Francesco Baino, Roberto Frairia, Chiara Vitale-Brovarone, and Rosa A. Canuto. "Key role of the expression of bone morphogenetic proteins in increasing the osteogenic activity of osteoblast-like cells exposed to shock waves and seeded on bioactive glass-ceramic scaffolds for bone tissue engineering." Journal of Biomaterials Applications 29, no. 5 (July 2, 2014): 728–36. http://dx.doi.org/10.1177/0885328214541974.
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In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine.
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Li, Yuwan, Ziming Liu, Yaping Tang, Qinghong Fan, Wei Feng, Changqi Luo, Guangming Dai, et al. "Three-dimensional silk fibroin scaffolds enhance the bone formation and angiogenic differentiation of human amniotic mesenchymal stem cells: a biocompatibility analysis." Acta Biochimica et Biophysica Sinica 52, no. 6 (May 11, 2020): 590–602. http://dx.doi.org/10.1093/abbs/gmaa042.
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Abstract Silk fibroin (SF) is a fibrous protein with unique mechanical properties, adjustable biodegradation, and the potential to drive differentiation of mesenchymal stem cells (MSCs) along the osteogenic lineage, making SF a promising scaffold material for bone tissue engineering. In this study, hAMSCs were isolated by enzyme digestion and identified by multiple-lineage differentiation. SF scaffold was fabricated by freeze-drying, and the adhesion and proliferation abilities of hAMSCs on scaffolds were determined. Osteoblast differentiation and angiogenesis of hAMSCs on scaffolds were further evaluated, and histological staining of calvarial defects was performed to examine the cocultured scaffolds. We found that hAMSCs expressed the basic surface markers of MSCs. Collagen type I (COL-I) expression was observed on scaffolds cocultured with hAMSCs. The scaffolds potentiated the proliferation of hAMSCs and increased the expression of COL-I in hAMSCs. The scaffolds also enhanced the alkaline phosphatase activity and bone mineralization, and upregulated the expressions of osteogenic-related factors in vitro. The scaffolds also enhanced the angiogenic differentiation of hAMSCs. The cocultured scaffolds increased bone formation in treating critical calvarial defects in mice. This study first demonstrated that the application of 3D SF scaffolds co-cultured with hAMSCs greatly enhanced osteogenic differentiation and angiogenesis of hAMSCs in vitro and in vivo. Thus, 3D SF scaffolds cocultured with hAMSCs may be a better alternative for bone tissue engineering.
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Gebauer, Michaela, and Arne Skerra. "Engineered Protein Scaffolds as Next-Generation Therapeutics." Annual Review of Pharmacology and Toxicology 60, no. 1 (January 6, 2020): 391–415. http://dx.doi.org/10.1146/annurev-pharmtox-010818-021118.
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The concept of engineering robust protein scaffolds for novel binding functions emerged 20 years ago, one decade after the advent of recombinant antibody technology. Early examples were the Affibody, Monobody (Adnectin), and Anticalin proteins, which were derived from fragments of streptococcal protein A, from the tenth type III domain of human fibronectin, and from natural lipocalin proteins, respectively. Since then, this concept has expanded considerably, including many other protein templates. In fact, engineered protein scaffolds with useful binding specificities, mostly directed against targets of biomedical relevance, constitute an area of active research today, which has yielded versatile reagents as laboratory tools. However, despite strong interest from basic science, only a handful of those protein scaffolds have undergone biopharmaceutical development up to the clinical stage. This includes the abovementioned pioneering examples as well as designed ankyrin repeat proteins (DARPins). Here we review the current state and clinical validation of these next-generation therapeutics.
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Kim, Haeri, Hanjun Hwangbo, YoungWon Koo, and GeunHyung Kim. "Fabrication of Mechanically Reinforced Gelatin/Hydroxyapatite Bio-Composite Scaffolds by Core/Shell Nozzle Printing for Bone Tissue Engineering." International Journal of Molecular Sciences 21, no. 9 (May 11, 2020): 3401. http://dx.doi.org/10.3390/ijms21093401.
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In tissue engineering, biocompatible scaffolds are used as 3D cell niches to provide a similar environment to that of native tissue for seeded cells to regenerate the target tissue. When engineering bone tissue, high mechanical strength and calcium phosphate composition are essential factors to consider. In this study, we fabricated biocompatible composite scaffolds composed of synthetic polymers (polycaprolactone (PCL) and poly (vinyl alcohol) (PVA)), natural polymers (gelatin and collagen) and bioceramic (hydroxyapatite; HA) for bone tissue engineering. The synthetic polymers were used to enhance the mechanical properties of the composite scaffolds while the natural protein-based polymers were used to enhance various cellular activities, such as cell adhesion and proliferation. Meanwhile, the bioceramic was introduced to promote osteogenic differentiation. Composite scaffolds were evaluated for their physical characteristics, such as mechanical, swelling and protein absorbing properties as well as biological properties (cell proliferation, alkaline phosphatase (ALP) activities and calcium deposition) with human osteoblast-like cells (MG63). Consequently, incorporation of hydroxyapatite into the gelatin/PVA (C-GPH) scaffold showed 5-fold and 1.5-fold increase in calcium deposition and ALP activities, respectively compared to gelatin/PVA scaffold (C-GP). Moreover, compressive modulus also increased 1.8-fold. Integration of PCL core into gelatin/PVA/hydroxyapatite scaffold (C-PGPH) further amplified the compressive modulus 1.5-fold. In conclusion, the scaffold that is reinforced with HA particles and integrated with PCL core of the struts showed significant potential in field of bone tissue engineering.
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Perry, Nicole A., Tamer S. Kaoud, Oscar O. Ortega, Ali I. Kaya, David J. Marcus, John M. Pleinis, Sandra Berndt, et al. "Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification." Proceedings of the National Academy of Sciences 116, no. 3 (December 27, 2018): 810–15. http://dx.doi.org/10.1073/pnas.1819230116.
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Scaffold proteins tether and orient components of a signaling cascade to facilitate signaling. Although much is known about how scaffolds colocalize signaling proteins, it is unclear whether scaffolds promote signal amplification. Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signal amplification by a scaffold protein. We found that arrestin-3 exhibited >15-fold higher affinity for inactive JNK3 than for active JNK3, and this change involved a shift in the binding site following JNK3 activation. We used systems biochemistry modeling and Bayesian inference to evaluate how the activation of upstream kinases contributed to JNK3 phosphorylation. Our combined experimental and computational approach suggested that the catalytic phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3. Finally, we showed that the release of activated JNK3 was critical for signal amplification. Collectively, our data suggest a “conveyor belt” mechanism for signal amplification by scaffold proteins. This mechanism informs on a long-standing mystery for how few upstream kinase molecules activate numerous downstream kinases to amplify signaling.
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Ledda, Mario, Miriam Merco, Antonio Sciortino, Elisa Scatena, Annalisa Convertino, Antonella Lisi, and Costantino Del Gaudio. "Biological Response to Bioinspired Microporous 3D-Printed Scaffolds for Bone Tissue Engineering." International Journal of Molecular Sciences 23, no. 10 (May 11, 2022): 5383. http://dx.doi.org/10.3390/ijms23105383.
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The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell–scaffold interaction and the integration with the surrounding biological tissue. Indeed, mimicking the natural extracellular matrix (ECM) of the tissue to be healed represents a further optimization that can limit a possible morphological mismatch between the scaffold and the tissue itself. For this aim, and referring to bone tissue engineering, polylactic acid (PLA) scaffolds were 3D printed with a microstructure inspired by the trabecular architecture and biologically evaluated by means of human osteosarcoma SAOS-2 cells. The cells were seeded on two types of scaffolds differing for the designed pore size (i.e., 400 and 600 µm), showing the same growth exponential trend found in the control and no significant alterations in the actin distribution. The microporous structure of the two tested samples enhanced the protein adsorption capability and mRNA expression of markers related to protein synthesis, proliferation, and osteoblast differentiation. Our findings demonstrate that 3D-printed scaffolds support the adhesion, growth, and differentiation of osteoblast-like cells and the microporous architecture, mimicking the natural bone hierarchical structure, and favoring greater bioactivity. These bioinspired scaffolds represent an interesting new tool for bone tissue engineering and regenerative medicine applications.
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Smith, S. E., R. A. White, D. A. Grant, and S. A. Grant. "The Use of a Green Fluorescent Protein Porcine Model to Evaluate Host Tissue Integration into Extracellular Matrix Derived Bionanocomposite Scaffolds." International Journal of Tissue Engineering 2015 (January 8, 2015): 1–10. http://dx.doi.org/10.1155/2015/586493.
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When using heterogeneous extracellular matrix (ECM) derived scaffolds for soft tissue repair, current methods of in vivo evaluation can fail to provide a clear distinction between host collagen and implanted scaffolds making it difficult to assess host tissue integration and remodeling. The purpose of this study is both to evaluate novel scaffolds conjugated with nanoparticles for host tissue integration and biocompatibility and to assess green fluorescent protein (GFP) expressing swine as a new animal model to evaluate soft tissue repair materials. Human-derived graft materials conjugated with nanoparticles were subcutaneously implanted into GFP expressing swine to be evaluated for biocompatibility and tissue integration through histological scoring and confocal imaging. Histological scoring indicates biocompatibility and remodeling of the scaffolds with and without nanoparticles at 1, 3, and 6 months. Confocal microscope images display host tissue integration into scaffolds although nonspecificity of GFP does not allow for quantification of integration. However, the confocal images do allow for spatial observation of host tissue migration into the scaffolds at different depths of penetration. The study concludes that the nanoparticle scaffolds are biocompatible and promote integration and that the use of GFP expressing swine can aid in visualizing the scaffold/host interface and host cell/tissue migration.
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Alqahtani, Q., S. H. Zaky, A. Patil, E. Beniash, H. Ray, and C. Sfeir. "Decellularized Swine Dental Pulp Tissue for Regenerative Root Canal Therapy." Journal of Dental Research 97, no. 13 (August 1, 2018): 1460–67. http://dx.doi.org/10.1177/0022034518785124.
Full textAbstract:
In the current theme of dental pulp regeneration, biological and synthetic scaffolds are becoming a potential therapy for pulp revitalization. The goal is to provide a suitable environment for cellular infiltration, proliferation, and differentiation. The extracellular matrix (ECM) represents a natural scaffold material resembling the native tissue chemical and mechanical properties. In the past few years, ECM-based scaffolds have shown promising results in terms of progenitor cells recruitment, promotion of constructive remodeling, and modulation of host response. These properties make ECM-derived scaffolds an ideal candidate for pulp regenerative therapy. Development of strategies for clinically relevant tissue engineering using dental pulp extracellular matrix (DP-ECM) can provide an alternative to conventional root canal treatment. In this work, we successfully decellularized ECM derived from porcine dental pulp. The resulting scaffold was characterized using immunostaining (collagen type I, dentin matrix protein 1, dentin sialoprotein, and Von Willebrand factor) and enzyme-linked immunosorbent assay (transforming growth factor β, vascular endothelial growth factor, and basic fibroblast growth factor) for extracellular proteins where the ECM retained its proteins and significant amount of growth factors. Furthermore, a pilot in vivo study was conducted where the matrix was implanted for 8 wk in a dog root canal model. Our in vitro and preliminary in vivo data show that the decellularized ECM supports cellular infiltration together with the expression of pulp-dentin and vascular markers (DSP and CD31) compared to the controls. Herein, we show the feasibility to produce a decellularized ECM scaffold and validate the concept of using ECM-based scaffolds for pulp regeneration.
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Koç, Aysel, Günter Finkenzeller, A. Eser Elçin, G. Björn Stark, and Y. Murat Elçin. "Evaluation of adenoviral vascular endothelial growth factor-activated chitosan/hydroxyapatite scaffold for engineering vascularized bone tissue using human osteoblasts: In vitro and in vivo studies." Journal of Biomaterials Applications 29, no. 5 (July 25, 2014): 748–60. http://dx.doi.org/10.1177/0885328214544769.
Full textAbstract:
Bone tissue is dependent on an efficient blood supply to ensure delivery of nutrients and oxygen. One method to acquire a vascular-engineered bone tissue could be the use of an angiogenic gene-activated scaffold. In the current study, porous chitosan/hydroxyapatite (C/HA) scaffolds were fabricated via freeze-drying with desired pore size, and then combined with the adenoviral vector encoding vascular endothelial growth factor and green fluorescence protein (Ad-VEGF). Human osteoblasts were cultured and seeded on characterized scaffolds. The attachment, proliferation, and differentiation of cells on gene-activated and unactivated C/HA scaffolds were evaluated in vitro and in vivo by histo- and immunohistochemistry. Findings confirmed that human osteoblasts cultured on gene-activated C/HA scaffold secreted vascular endothelial growth factor, besides maintaining its characteristic phenotype with specific extracellular matrix production. In vivo experiments indicated that scaffolds were tissue biocompatible, and that gene-activated scaffold provided a suitable environment for neovessel formation by recruiting host endothelial cells into the newly forming ectopic bone-like tissue. This study revealed that the Ad-VEGF-activated C/HA composite scaffold has potential for vascular bone regeneration applications.
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Cheng, Cheng-Hsin, Yi-Hui Lai, Yi-Wen Chen, Chun-Hsu Yao, and Kuo-Yu Chen. "Immobilization of bone morphogenetic protein-2 to gelatin/avidin-modified hydroxyapatite composite scaffolds for bone regeneration." Journal of Biomaterials Applications 33, no. 9 (February 10, 2019): 1147–56. http://dx.doi.org/10.1177/0885328218820636.
Full textAbstract:
Bone scaffold surface characterization is important for improving cell adhesion, migration, and differentiation. In this study, bone morphogenetic protein-2 (BMP-2) was immobilized to the surface of the gelatin/hydroxyapatite composite using avidin–biotin binding system to produce a bone-tissue engineering scaffold. Firstly, hydroxyapatite particles reacted with hexamethylene diisocyanate and then the terminal group was converted into a primary amine group. Avidin was then immobilized on the surfaces of hydroxyapatite particles using N-ethyl-N′-(3-(dimethylamino)propyl) carbodiimide and N-hydroxysuccinimide as coupling agents. Gelatin was blended with avidin-modified hydroxyapatite and pure hydroxyapatite to obtain gelain/hydroxyapatite composite. The composite was then cross-linked with glutaraldehyde. Finally, biotin-conjugated BMP-2 was immobilized on the surface of the composite via avidin–biotin binding. In vitro study indicated that BMP-2-immobilized composite film had a higher ALP activity than that composite film without BMP-2. The composite scaffolds were then implanted into rabbit skulls to check bone-tissue regeneration. Ultrasound and micro-CT scans demonstrated that neovascularization and new bone formation in the BMP-2-immobilized composite scaffolds were higher than those in composite scaffolds without BMP-2. Histological evaluation result was similar to that of the micro-CT. Therefore, the surface immobilization of BMP-2 could effectively improve osteogenesis in the gelatin/hydroxyapatite composite scaffold.
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Heo, S. J., S. E. Kim, Yong Taek Hyun, D. H. Kim, Hyang Mi Lee, Yeong Maw Hwang, S. A. Park, and Jung Woog Shin. "In Vitro Evaluation of Poly ε-Caprolactone/Hydroxyapatite Composite as Scaffolds for Bone Tissue Engineering with Human Bone Marrow Stromal Cells." Key Engineering Materials 342-343 (July 2007): 369–72. http://dx.doi.org/10.4028/www.scientific.net/kem.342-343.369.
Full textAbstract:
This study evaluated the potential of the PCL (poly -caprolactone)/HA(Hydroxyapatite) composite materials as a scaffold for bone regeneration. For this, we fabricated scaffolds utilizing salt leaching method. The PCL/HA composite scaffolds were prepared with various HA contents (20wt%, 40wt%, 60 wt %). To ensure the potential for the scaffolds, porosity tests were conducted along with SEM observations. The porosity decreased with the increase of the contents of HA particles. The porosity of the composite with the highest contents of HA was still adoptable (~85%). In addition, the PCL/HA composite scaffolds were evaluated for their ability of osteogenic differentiation with human bone marrow stromal cell (hBMSC) in vitro. Alkaline phosphatase (ALP) activity, markers for osteoblastic differentiation, and total protein contents were evaluated in hBMSCs following 14 days of cultivation. The addition of HA particles enhanced proliferation of hBMSC during the test. Also, the differentiation ability of the cells was increased as HA particles were added. In this study, we concluded that PCL/HA composite scaffolds has great potential as a scaffold for bone tissue engineering.
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Saraogi, Ishu, and Andrew D. Hamilton. "α-Helix mimetics as inhibitors of protein–protein interactions." Biochemical Society Transactions 36, no. 6 (November 19, 2008): 1414–17. http://dx.doi.org/10.1042/bst0361414.
Full textAbstract:
The inhibition of protein–protein interactions using small molecules is a viable approach for the treatment of a range of pathological conditions that result from a malfunctioning of these interactions. Our strategy for the design of such agents involves the mimicry of side-chain residues on one face of the α-helix; these residues frequently play a key role in mediating protein–protein interactions. The first-generation terphenyl scaffold, with a 3,2′,2″-substitution pattern, is able to successfully mimic key helix residues and disrupt therapeutically relevant interactions, including the Bcl-XL–Bak and the p53–hDM2 (human double minute 2) interactions that are implicated in cancer. The second- and third-generation scaffolds have resulted in greater synthetic accessibility and more drug-like character in these molecules.
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Rittipakorn, Pawornwan, Nuttawut Thuaksuban, Katanchalee Mai-ngam, Satrawut Charoenla, and Warobon Noppakunmongkolchai. "Bioactivity of a Novel Polycaprolactone-Hydroxyapatite Scaffold Used as a Carrier of Low Dose BMP-2: An In Vitro Study." Polymers 13, no. 3 (February 1, 2021): 466. http://dx.doi.org/10.3390/polym13030466.
Full textAbstract:
Scaffolds of polycaprolactone-30% hydroxyapatite (PCL-30% HA) were fabricated using melt stretching and multilayer deposition (MSMD), and the in vitro response of osteoblasts to the scaffolds was assessed. In group A, the scaffolds were immersed in 10 µg/mL bone morphogenetic protein-2 (BMP-2) solution prior to being seeded with osteoblasts, and they were cultured in the medium without BMP-2. In group B, the cell-scaffold constructs without BMP-2 were cultured in medium containing 10 µg/mL BMP-2. The results showed greater cell proliferation in group A. The upregulation of runt-related transcription factor 2 and osteocalcin genes correlated with the release of BMP-2 from the scaffolds. The PCL-30% HA MSMD scaffolds appear to be suitable for use as osteoconductive frameworks and BMP-2 carriers.