User:Biotechie86/sandbox

I am working to build an article about Tissue Engineering by self assembly. It is technique that allows researchers to create tissue engineering scaffolds from cellular products rather than external products.

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Introduction
Tissue Engineering is a scientific discipline which aims to repair and replace biological functions by combining biological sciences with engineering principles. From its beginnings Tissue Engineering has been focused on a simple formula for creating biological constructs with mechanical stability enough to hold their shape and resist mechanical forces in the body. This formula is to isolate and expand human or animal cells, and then to seed these cells onto a scaffold for mechanical stability. While all manner of cells have been used in these experiments, the scaffold has proven to be a much richer area for exploration. Initial scaffolds were composed of reconstituted natural fiber matrices, which provided a very biologically similar environment, but failed to provide the mechanical support needed to resist forces in demanding applications such as blood vessel replacements. These scaffolds were improved mechanically by switching to synthetic scaffolds such as Dacron, but this represented a major trade off for bio-similarity and bio-compatibility. Since these scaffolds were recognized as foreign by both the seeded cells and the body, implants would be rejected and cells would not performs as they do in natural conditions.

Tissue Engineering by Self Assembly or TESA attempts to address both of these issues by forming a purely biological scaffold which maintains a natural cellular environment and uses long culture times to achieve very strong mechanical properties needed for clinical applications. This combination has lead to the development of the first commercially viable artificial blood vessel to be implanted in human patients.

Definition
Tissue Engineering by Self Assembly (TESA) uses advanced culture techniques to induce human cells to create a mechanically robust, purely biological scaffold. This self assembled matrix can then be further processed until many different forms for various applications.

In the most basic form of TESA, human skin fibroblasts (HSFs) are grown in culture media supplemented with chemical factors shown to induce the production of large quantities of extracellular matrix proteins(ECM), especially collagen. These cells along with their matrix continue to grow over the course of several weeks resulting in the formation of a very thick and dense layer of biologically active and mechanically robust material. Since the cells have assembled their own matrix, it remains very true to the biological conditions the cells expect, this results in continued cellular activity. The layers of collagen produced by the cells are similar to collagen matrices produced by early tissue engineering researchers, but TESA avoids the mechanically disastrous processes of dissolving and reconstituting these proteins.

Sheet-Based Tissue Engineering (SBTE)
The first clinical application of TESA was built using a sheet based approach. In sheet-based tissue engineering (SBTE), the cellular material is harvested from culture as one large living sheet. For blood vessel replacement studies, this sheet is then rolled into a tube and allowed to mature for several more weeks in culture. This additional maturation phase allows the multiple layers of biomaterial to fuse into a homogeneous construct. Once fused the tube can then be implanted or further processed. In one clinical study of SBTE, this tube was devitalized and then a second layer of sheet material was rolled around it and again allowed to mature.

SBTE also holds potential in clinical applications requiring a large, thin, strong patch of biomaterial such as aortic ambolism repair.

Thread-Based Tissue Engineering (TBTE)
When the scaffolds created by the TESA approach are processed into threads the demonstrate very high tensile strength. This allows the creation of purely biological threads. From these threads a variety of woven constructs is possible such as woven blood vessels or patches This technology creates very strong structures that mimic the success of STBE while circumventing the long maturation phase of layer fusion.

Particle-Based Tissue Engineering (PBTE)
Another area where TESA is being explored is whole organ tissue engineering. This field focuses on recreating three dimensional organs. This is a complicated task in part because of a need for a strong, porous, biocompatible scaffold to support cells in a form resembling natural organs. TESA addresses this problem by utilizing small particles of cell synthesized biomaterial cast into various molds to create three dimensional porous material.

A further application of these scaffolds particles could be tissue fillers for reconstructive surgery.

First in Human Trials
A TESA approach lead by Cytograft Tissue Engineering implanted the first completly biological artifical blood vessel.

Autologous and Allogeneic Approaches
The TESA approach has been developed for both a allogenic and autologous application. Autologus approaches avoid immune reactions by implanting cells taken from the patient who receives the graft. In other words, the donor of the cells is also the recipient, this limits the body's ability to recognize the graft as "foreign". TESA is also possible in a Allogenic procedure, relying on donor cells from a different individual. In these cases the cells are removed from the final graft. In these decellularized procedures, the strong scaffold created by the donor cells is implanted in the patient, then the patient's cells populate and re-vitalize the implant.

Articles that I intend to cite and the important information conveyed by them.
-Nature Medicine 2006. Demonstrated in vivo anti-thrombogenicity and mechanical stability in canine and nude rat. Patient matched cell source -Faseb 1998. Establishment of the technology, shows the ability to create complex constructs using sheets SBTE -Lancet 2009. Human results SBTE -Materials Today 2011. Definition of TESA approach. References addressing "self assembly" 20-22. Figure 4 is a great schematic showing SBTE v. PBTE v. TBTE.

-"Spinning Spare Parts: Human threads could become off-the-shelf spare blood vessels." By Susan Young on May 3, 2012 http://www.technologyreview.com/news/427822/spinning-spare-parts/page/2/?p1=A2