Customized Ca–P/PHBV nanocomposite scaffolds for bone tissue engineering: design, fabrication, surface modification and sustained release of growth factor
TL;DR: Together with osteoconductive nanocomposite material and controlled growth factor delivery strategies, the use of SLS technique to form complex scaffolds will provide a promising route towards individualized bone tissue regeneration.
Abstract: Integrating an advanced manufacturing technique, nanocomposite material and controlled delivery of growth factor to form multifunctional tissue engineering scaffolds was investigated in this study. Based on calcium phosphate (Ca–P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite microspheres, three-dimensional Ca–P/PHBV nanocomposite scaffolds with customized architecture, controlled porosity and totally interconnected porous structure were successfully fabricated using selective laser sintering (SLS), one of the rapid prototyping technologies. The cytocompatibility of sintered Ca–P/PHBV nanocomposite scaffolds, as well as PHBV polymer scaffolds, was studied. For surface modification of nanocomposite scaffolds, gelatin was firstly physically entrapped onto the scaffold surface and heparin was subsequently immobilized on entrapped gelatin. The surface-modification improved the wettability of scaffolds and provided specific binding site between conjugated heparin and the growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2). The surface-modified Ca–P/PHBV nanocomposite scaffolds loaded with rhBMP-2 significantly enhanced the alkaline phosphatase activity and osteogenic differentiation markers in gene expression of C3H10T1/2 mesenchymal stem cells. Together with osteoconductive nanocomposite material and controlled growth factor delivery strategies, the use of SLS technique to form complex scaffolds will provide a promising route towards individualized bone tissue regeneration.
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TL;DR: In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described.
Abstract: 3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing.
1,288 citations
Additional excerpts
...For SLS, common materials used are PCL and HA [92,96,97], PCL and β-TCP with collagen coating [98], Ca-P/PHBV and CHAp/PLLA [99,100], and PVA [101]....
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...Ca-P/PHBV and CHAp/PLLA [99,100], and PVA [101]....
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01 Jan 2009
TL;DR: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks.
Abstract: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.
942 citations
TL;DR: This article provides a concise review of recent advances in the R & D of 3D printing of bone tissue engineering scaffolds and presents the philosophy and research in the designing and fabrication of Bone tissue Engineering scaffolds through3D printing.
343 citations
Cites background from "Customized Ca–P/PHBV nanocomposite ..."
...Both in vitro and in vivo results demonstrated that the rhBMP-2 conjugated Ca–P/PHBV scaffolds could greatly improve osteogenesis [79]....
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TL;DR: The characteristics features of SLS and the materials that have been developed for are reviewed together with a discussion on the principles of the above-mentioned manufacturing technique.
Abstract: Selective laser sintering (SLS) is a solid freeform fabrication technique, developed by Carl Deckard for his master’s thesis at the University of Texas, patented in 1989. SLS manufacturing is a technique that produces physical models through a selective solidification of a variety of fine powders. SLS technology is getting a great amount of attention in the clinical field. In this paper the characteristics features of SLS and the materials that have been developed for are reviewed together with a discussion on the principles of the above-mentioned manufacturing technique. The applications of SLS in tissue engineering, and at-large in the biomedical field, are reviewed and discussed.
302 citations
Cites background from "Customized Ca–P/PHBV nanocomposite ..."
...[17–19] proposed the use of calcium phosphate (Ca–P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite microspheres for the manufacturing of three-dimensional Ca–P/PHBV scaffolds via SLS for bone tissue engineering applications....
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TL;DR: An extensive overview of different AM techniques employed for the development of tissue‐engineered constructs made of different materials, by highlighting their principles and technological solutions is given.
Abstract: 'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions.
297 citations
Cites methods from "Customized Ca–P/PHBV nanocomposite ..."
...…with bovine serum albumin (BSA) as model protein (Duan and Wang, 2010b) or by physically entrapping gelatine on the scaffold surface (Duan et al., 2011b) and binding human bone morphogenetic protein-2 (BMP-2) to heparin immobilized on gelatinemodified scaffold surface (Duan and Wang, 2010a)....
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...A number of recent studies have reported on the development of poly(hydroxybutyrate-co-hydroxyvalerate)– tricalcium phosphate (PHBV–TCP) scaffolds by applying SLS to composite microspheres (Figure 4c, d) (Duan and Wang, 2010a, 2010b; Duan et al., 2010, 2011a, 2011b)....
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...The bioactivity of the composite scaffolds was enhanced by loading the microspheres with bovine serum albumin (BSA) as model protein (Duan and Wang, 2010b) or by physically entrapping gelatine on the scaffold surface (Duan et al., 2011b) and binding human bone morphogenetic protein-2 (BMP-2) to…...
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References
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TL;DR: New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
5,470 citations
"Customized Ca–P/PHBV nanocomposite ..." refers methods in this paper
...…sintered scaffolds (both bar-shaped and rod-shaped) was examined using scanning electron microscopes (LEO 1530 FE-SEM or Hitachi S-3400N SEM) and the porosity of scaffolds was measured using a density kit and an electronic balance on the basis of Archimedes principle (Karageorgiou & Kaplan 2005)....
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25 Mar 2014
TL;DR: In this article, the authors present a survey of Indian cities in terms of Latitude (°) +N/-SLongitude (−) +E/-W New Delhi India C V Raman Science Club 28.616 77.195
Abstract: FlagCityCountrySchoolLatitude (°) +N/-SLongitude (°) +E/-W New Delhi India C V Raman Science Club 28.616 77.195
2,100 citations
TL;DR: This review focuses on aspects of heparin structure and conformation, which are important for its interactions with proteins, and describes the interaction ofheparin and heparan sulfate with selected families of heParin-binding proteins.
Abstract: Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans, has numerous important biological activities, associated with its interaction with diverse proteins. Heparin is widely used as an anticoagulant drug based on its ability to accelerate the rate at which antithrombin inhibits serine proteases in the blood coagulation cascade. Heparin and the structurally related heparan sulfate are complex linear polymers comprised of a mixture of chains of different length, having variable sequences. Heparan sulfate is ubiquitously distributed on the surfaces of animal cells and in the extracellular matrix. It also mediates various physiologic and pathophysiologic processes. Difficulties in evaluating the role of heparin and heparan sulfate in vivo may be partly ascribed to ignorance of the detailed structure and sequence of these polysaccharides. In addition, the understanding of carbohydrate-protein interactions has lagged behind that of the more thoroughly studied protein-protein and protein-nucleic acid interactions. The recent extensive studies on the structural, kinetic, and thermodynamic aspects of the protein binding of heparin and heparan sulfate have led to an improved understanding of heparin-protein interactions. A high degree of specificity could be identified in many of these interactions. An understanding of these interactions at the molecular level is of fundamental importance in the design of new highly specific therapeutic agents. This review focuses on aspects of heparin structure and conformation, which are important for its interactions with proteins. It also describes the interaction of heparin and heparan sulfate with selected families of heparin-binding proteins.
1,722 citations
"Customized Ca–P/PHBV nanocomposite ..." refers background in this paper
...Heparin, a sulphated polysaccharide belonging to the glycosaminoglycans family, is known to have the binding affinity with a number of growth factors and is thus capable of blocking the degradation of the growth factors and prolonging their release time (Capila & Linhardt 2002; Jiao et al. 2007)....
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TL;DR: In this paper, the properties of the organic matrix as well as the geometrical arrangement of the two components might have a much larger influence on the properties than traditionally assumed, and some recent results from experiment and numerical modeling leading to these ideas are reviewed.
Abstract: Bone is a hierarchically structured material with remarkable mechanical performance which may serve as a model for the development of biomimetic materials. Understanding its properties is essential for the assessment of diseases such as osteoporosis. This will lead to a critical evaluation of current therapies and aid in their more targeted development. While the full hierarchical structure of bone is extremely complex and variable, its basic building block, the mineralized collagen fibril, is rather universal. Due to the progress in experimental methods to characterize materials at the nanoscale, new insights have been gained into the structure/mechanical function relation in this nanocomposite. The amount of mineral is usually thought to determine the stiffness of the material, but recent results suggest that the properties of the organic matrix as well as the geometrical arrangement of the two components might have a much larger influence on the properties than traditionally assumed. Some recent results from experiment and numerical modeling leading to these ideas are reviewed.
1,128 citations
"Customized Ca–P/PHBV nanocomposite ..." refers background in this paper
...From material point of view, bone can be considered as a nanocomposite consisting of organic matrix (mainly collagen) and inorganic nanofillers (mainly bone apatite), which are inserted in a parallel way into the collagen fibrils (Fratzl et al. 2004; Murugan & Ramakrishna 2005)....
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TL;DR: The current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in sp heroid culture, manipulation, and analysis techniques are reviewed.
Abstract: Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.
1,107 citations
"Customized Ca–P/PHBV nanocomposite ..." refers background in this paper
...Bone and Tissue Engineering’. arch 2010 ay 2010 S615 spheroid or cell sheet for transplantation (Matsuda et al. 2007; Lin & Chang 2008; Mason & Dunnill 2009)....
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