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Principles Of Tissue Engineering 3rd Edition - [PDF] [EPUB] Principles Of Tissue Engineering. 3rd Edition First published in , Principles of. principles of Tissue Engineering to tissue and organ regeneration. As more and more The Biomedical Engineering Handbook, 3rd terney.info Taylor & Francis. and j vacanti. principles of tissue engineering 3rd edition pdf download - engineering by the field the third edition provides a much needed update of the rapid.
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Carbon nanotubes are among the numerous candidates for tissue engineering scaffolds since they are biocompatible , resistant to biodegradation and can be functionalized with biomolecules.
However, the possibility of toxicity with non-biodegradable nano-materials is not fully understood. A high porosity and an adequate pore size are necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients. Biodegradability is often an essential factor since scaffolds should preferably be absorbed by the surrounding tissues without the necessity of a surgical removal.
The rate at which degradation occurs has to coincide as much as possible with the rate of tissue formation: this means that while cells are fabricating their own natural matrix structure around themselves, the scaffold is able to provide structural integrity within the body and eventually it will break down leaving the newly formed tissue which will take over the mechanical load.
Injectability is also important for clinical uses. Recent research on organ printing is showing how crucial a good control of the 3D environment is to ensure reproducibility of experiments and offer better results. Materials[ edit ] Many different materials natural and synthetic, biodegradable and permanent have been investigated. Examples of these materials are collagen and some polyesters. New biomaterials have been engineered to have ideal properties and functional customization: injectability, synthetic manufacture, biocompatibility , non-immunogenicity, transparency, nano-scale fibers, low concentration, resorption rates, etc.
PuraMatrix, originating from the MIT labs of Zhang, Rich, Grodzinsky and Langer is one of these new biomimetic scaffold families which has now been commercialized and is impacting clinical tissue engineering. A commonly used synthetic material is PLA - polylactic acid. This is a polyester which degrades within the human body to form lactic acid , a naturally occurring chemical which is easily removed from the body. While these materials have well maintained mechanical strength and structural integrity, they exhibit a hydrophobic nature.
This hydrophobicity inhibits their biocompatibility, which makes them less effective for in vivo use as tissue scaffolding. By combining the two different types of materials, researchers are trying to create a synergistic relationship that produces a more biocompatible tissue scaffolding. Proteic materials, such as collagen or fibrin , and polysaccharidic materials, like chitosan  or glycosaminoglycans GAGs , have all proved suitable in terms of cell compatibility, but some issues with potential immunogenicity still remains.
Among GAGs hyaluronic acid , possibly in combination with cross linking agents e. Functionalized groups of scaffolds may be useful in the delivery of small molecules drugs to specific tissues. Recently a range of nanocomposites biomaterials are fabricated by incorporating nanomaterials within polymeric matrix to engineer bioactive scaffolds.
Upon deconstruction, these sheets can be useful in cell-based high-throughput screening and drug discovery. Each of these techniques presents its own advantages, but none are free of drawbacks.
Nanofiber self-assembly[ edit ] Molecular self-assembly is one of the few methods for creating biomaterials with properties similar in scale and chemistry to that of the natural in vivo extracellular matrix ECM , a crucial step toward tissue engineering of complex tissues. Textile technologies[ edit ] These techniques include all the approaches that have been successfully employed for the preparation of non-woven meshes of different polymers.
In particular, non-woven polyglycolide structures have been tested for tissue engineering applications: such fibrous structures have been found useful to grow different types of cells. The principal drawbacks are related to the difficulties in obtaining high porosity and regular pore size.
Solvent casting and particulate leaching[ edit ] Solvent casting and particulate leaching SCPL allows for the preparation of structures with regular porosity, but with limited thickness. First, the polymer is dissolved into a suitable organic solvent e. Such porogen can be an inorganic salt like sodium chloride , crystals of saccharose , gelatin spheres or paraffin spheres.
The size of the porogen particles will affect the size of the scaffold pores, while the polymer to porogen ratio is directly correlated to the amount of porosity of the final structure. After the polymer solution has been cast the solvent is allowed to fully evaporate, then the composite structure in the mold is immersed in a bath of a liquid suitable for dissolving the porogen: water in the case of sodium chloride, saccharose and gelatin or an aliphatic solvent like hexane for use with paraffin.
Once the porogen has been fully dissolved, a porous structure is obtained. Other than the small thickness range that can be obtained, another drawback of SCPL lies in its use of organic solvents which must be fully removed to avoid any possible damage to the cells seeded on the scaffold. Gas foaming[ edit ] To overcome the need to use organic solvents and solid porogens, a technique using gas as a porogen has been developed.
First, disc-shaped structures made of the desired polymer are prepared by means of compression molding using a heated mold. The discs are then placed in a chamber where they are exposed to high pressure CO2 for several days.
The pressure inside the chamber is gradually restored to atmospheric levels.
During this procedure the pores are formed by the carbon dioxide molecules that abandon the polymer, resulting in a sponge-like structure.
The main problems resulting from such a technique are caused by the excessive heat used during compression molding which prohibits the incorporation of any temperature labile material into the polymer matrix and by the fact that the pores do not form an interconnected structure.
Emulsification freeze-drying[ edit ] This technique does not require the use of a solid porogen like SCPL. First, a synthetic polymer is dissolved into a suitable solvent e. Before the two phases can separate, the emulsion is cast into a mold and quickly frozen by means of immersion into liquid nitrogen. The frozen emulsion is subsequently freeze-dried to remove the dispersed water and the solvent, thus leaving a solidified, porous polymeric structure.
While emulsification and freeze-drying allow for a faster preparation when compared to SCPL since it does not require a time consuming leaching step , it still requires the use of solvents. Moreover, pore size is relatively small and porosity is often irregular. Freeze-drying by itself is also a commonly employed technique for the fabrication of scaffolds. In particular, it is used to prepare collagen sponges: collagen is dissolved into acidic solutions of acetic acid or hydrochloric acid that are cast into a mold, frozen with liquid nitrogen and then lyophilized.
Thermally induced phase separation[ edit ] Similar to the previous technique, the TIPS phase separation procedure requires the use of a solvent with a low melting point that is easy to sublime. For example, dioxane could be used to dissolve polylactic acid, then phase separation is induced through the addition of a small quantity of water: a polymer-rich and a polymer-poor phase are formed.
Following cooling below the solvent melting point and some days of vacuum-drying to sublime the solvent, a porous scaffold is obtained. In a typical electrospinning set-up, a solution is fed through a spinneret and a high voltage is applied to the tip.
The buildup of electrostatic repulsion within the charged solution, causes it to eject a thin fibrous stream.
A mounted collector plate or rod with an opposite or grounded charge draws in the continuous fibers, which arrive to form a highly porous network. The primary advantages of this technique are its simplicity and ease of variation. At a laboratory level, a typical electrospinning set-up only requires a high voltage power supply up to 30 kV , a syringe, a flat tip needle and a conducting collector.
For these reasons, electrospinning has become a common method of scaffold manufacture in many labs. By modifying variables such as the distance to collector, magnitude of applied voltage, or solution flow rate—researchers can dramatically change the overall scaffold architecture.
Historically, research on electrospun fibrous scaffolds dates back to at least the late s when Simon showed that electrospinning could be used to produced nano- and submicron-scale fibrous scaffolds from polymer solutions specifically intended for use as in vitro cell and tissue substrates.
This early use of electrospun lattices for cell culture and tissue engineering showed that various cell types would adhere to and proliferate upon polycarbonate fibers. It was noted that as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more rounded 3-dimensional morphology generally observed of tissues in vivo. First, a three-dimensional structure is designed using CAD software.
The porosity can be tailored using algorithms within the software. LaBP arranges small volumes of living cell suspensions in set high-resolution patterns. As of this study, only human skin tissue has been synthesized, though researchers project that "by integrating further cell types e. Engineered tissues generally lack an initial blood supply, thus making it difficult for any implanted cells to obtain sufficient oxygen and nutrients to survive, or function properly. Self-assembly[ edit ] Self-assembly methods have been shown to be promising methods for tissue engineering.
Self-assembly methods have the advantage of allowing tissues to develop their own extracellular matrix, resulting in tissue that better recapitulates biochemical and biomechanical properties of native tissue. Self-assembling engineered articular cartilage was introduced by Jerry Hu and Kyriacos A. Athanasiou in  and applications of the process have resulted in engineered cartilage approaching the strength of native tissue. To break down tissues into cells, researchers first have to dissolve the extracellular matrix that normally binds them together.
Once cells are isolated, they must form the complex structures that make up our natural tissues. Liquid-based template assembly[ edit ] The air-liquid surface established by Faraday waves is explored as a template to assemble biological entities for bottom-up tissue engineering. This liquid-based template can be dynamically reconfigured in a few seconds, and the assembly on the template can be achieved in a scalable and parallel manner.
Assembly of microscale hydrogels, cells, neuron-seeded micro-carrier beads, cell spheroids into various symmetrical and periodic structures was demonstrated with good cell viability. Formation of 3D neural network was achieved after day tissue culture. A recent innovative method of construction uses an ink-jet mechanism to print precise layers of cells in a matrix of thermoreversible gel. Endothelial cells, the cells that line blood vessels, have been printed in a set of stacked rings.
When incubated, these fused into a tube. The device is presented in a TED talk by Dr. Anthony Atala, M.