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In 2003, the NSF published a report titled "The Emergence of Tissue Engineering as a Research Field" , which gives a thorough description of the history of this field. While the semi-official definition of tissue engineering covers a broad range of applications, in practice the term has come to represent applications that repair or replace structural tissues (i.e., Bone , Cartilage , Blood Vessels , Bladder , etc...). These are tissues that function by virtue of their mechanical properties. A closely related (and older) field is Cell Transplantation . This field is concerned with the transplantation of cells that perform a specific biochemical function (e.g., an Artificial Pancreas , or an Artificial Liver ). The term Regenerative Medicine is often used synonymously with Tissue Engineering , although those involved in regenerative medicine place more emphasis on the use of Stem Cells to produce tissues. A typical tissue engineering solution consists of a number of parts as alluded to above. This article will discuss each part in turn, along with its implications. CELLS Tissue engineering solves problems by using living cells as engineering materials. These could be artificial Skin that includes living Fibroblast s, Cartilage repaired with living Chondrocyte s, or other types of cells used in other ways. Cells became available as engineering materials when scientists at Geron Corp. discovered how to extend Telomere s in 1998, producing an Immortalized Cell Line . Before this, laboratory cultures of healthy, noncancerous mammalian cells would only divide a fixed number of times, up to the Hayflick Limit . From fluid tissues such as Blood , cells are extracted by bulk methods, usually Centrifugation or Apheresis . From solid tissues, extraction is more difficult. Usually the tissue is minced, and then digested with the Enzyme s Trypsin or Collagenase to remove the Extracellular Matrix that holds the cells. After that, the cells are free floating, and extracted using centrifugation or aspheresis. Digestion with trypsin is very dependent on temperature. Higher temperatures digest the matrix faster, but create more damage. Collagenase is less temperature dependent, and damages fewer cells, but takes longer and is a more expensive reagent. Cells are often categorized by their source:
ENGINEERING MATERIALS Cells as found above are generally implanted or 'seeded' into an artificial structure capable of supporting Three-dimensional tissue formation. Such devices, usually referred to as scaffolds, serve at least one of the following purposes:
To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. 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 essential since scaffolds need to 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 neotissue, newly formed tissue which will take over the mechanical load. Many different materials (natural and synthetic, biodegradable and permanent) have been investigated. Most of these materials have been known in the medical field before the advent of tissue engineering as a research topic, being already employed as bioresorbable Sutures . Examples of these materials are Collagen or some linear Aliphatic Polyesters . 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. Similar materials are Polyglycolic Acid (PGA) and Polycaprolactone (PCL): their degradation mechanism is similar to that of PLA, but they exhibit respectively a faster and a slower rate of degradation compared to PLA. Scaffolds may also be constructed from natural materials: in particular different derivatives of the Extracellular Matrix have been studied to evaluate their ability to support cell growth. Proteic materials, such as collagen or Fibrin , and polysaccharidic materials, like Chitosan or Glycosaminoglycan s (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.g. Glutaraldehyde , Water Soluble Carbodiimide , etc...), is one of the possible choices as scaffold material. Functionalized groups of scaffolds may be useful in the delivery of small molecules (drugs) to specific tissues. SYNTHESIS OF TISSUE ENGINEERING SCAFFOLDS A number of different methods has been described in literature for preparing porous structures to be employed as tissue engineering scaffolds. Each of these techniques presents its own advantages, but none is devoid of drawbacks.
ASSEMBLY METHODS One of the continuing, persistent problems with tissue engineering is mass transport limitations. Engineered tissues generally lack an initial blood supply, thus making it difficult for any implanted cells to obtain sufficient oxygen and nutrients to survive, and/or function properly. It might be possible to print organs, or possibly entire organisms. A recent innovative method of construction uses an ink-jet mechanism to print precise layers of cells in a matrix of thermoreversable 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.Mironov et al., 2003 RECENT DEVELOPMENTS Dr. Anthony Atala of Wake Forest University has successfully implanted artificially grown bladders into seven human test subjects as part of a long-term experiment, with demonstrated positive benefits to the recipients thus far. [http://www.cnn.com/2006/HEALTH/conditions/04/03/engineered.organs/index.html Doctors grow organs from patients' own cells], '' CNN '', April 3, 2006 SEE ALSO
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