Progress and opportunities for tissue-engineered skin
MacNeil, Sheila. “Progress and opportunities for tissue-engineered skin.” Nature. Vol 445
pg.874-880. 22 Feb 2007.
Individuals who suffer a loss of both layers of skin (epidermis and dermis) more than a diameter of 4 cm usually cannot heal without a graft. In these cases surgeons will remove from healthy areas of the body a split-thickness graft that comprises of a full epidermis and partial dermis layer. The graft integrates with the wounded area and protects the area like a skin band-aid. The area the graft was taken from will be able to regenerate an epidermis layer as long as there are enough residual epidermal cells left in the remaining dermis layer. Although this method works well, sometimes it is not always best to create another wound to heal another depending on the person’s health—this is where skin tissue engineering is necessary.
Skin grafts must restore barrier function or promote healing, therefore engineered skin must do the same. Engineered skin is composed of the same cells naturally found in skin in a 3D structure: keratinocytes (for barrier) and fibroblasts (for strength and resilience). One of its major advantage is that skin cells can be cultured and grown at a much higher rate than in the human body, however, a major fallback is immune rejection to the cultured cells or support mediums. Some grafts use fetal bovine serum to sustain the cells that can cause an unwanted allergic response. Also a successful engineered skin graft is one where the individual’s own skin cells take over and replace the cells in the graft so near seamless integration of foreign and host tissue is necessary.
Skin grafts must also be a proper scaffold structure that allows angiogenesis to occur because without a blood source the graft will die and obviously not integrate with the surrounding skin. Cell migration needs to take place to aid in integration and replacement of cells also, so that is why artificial skin is so complex. There are substitutes that consist of just the epidermis layer, just the dermis layer, and few with both the epidermis layer and dermis layer (the most needed one).
Besides the clinical application, skin grafts can also aid researchers in learning about cell-to-cell extra-cellular interaction, regulation of pigmentation, disease penetration/invasion (i.e. melanoma), skin contraction, and many more specific mechanisms. This added bonus furthers motivation in finding a good skin graft. Currently the main goals to improve upon the already established research include ease of use, clinical efficacy and practicality, introducing TGFβ-family factors to promote wound healing and reduce scar formation, reducing graft contraction while increasing graft attachment
I chose this paper because it shows me how much the field of bioengineering has advanced, and yet, how much more it can broaden—it is amazing that skin was one of the first engineered tissue and yet there is still no perfect skin substitute. Skin is the largest human organ and the primary barrier that block harmful antigens from entering the body. The immune system is largely dependant on skin and so there is high motivation to find suitable skin substitutes for individuals with large surface wounds. Thus, for these reasons I believe major advances should continue to be made in this aspect of bioengineering.
6 comments:
Sweet article and excellent summary. On a personal note, the event that led me to became a bioengineer (and not ME or EE) occured when one of my close relatives got a third degree burn on significant portion of his body. The whole recovery process is extremely long, the pain-killers have devastating effects to daily life routine, and the recovered skin doesn't look natural or function naturally even after a decade. At the beginning you have to change bandages about once every week, which means that the doctor RIPS the bandage away from the burnt area, with layers of flesh and all. I really think researchers should take more interest in this field, as it'd mean a world to those people whose loved ones are involved.
Are there any other components in the engineered skin besides keratinocytes and fibroblasts? Any specific type of polymer or growth factors used? Also, aren't endothelial cells necessary for angiogenesis?
Whenever people ask me what bioengineers do when I tell them my major, the first thing that I tell them always would involve an example that goes something like this: "we're the ones who make tissue engineered skin for burn victims". That usually elicits the greatest "wow" factor. In fact, I believe that learning about skin regeneration via tissue engineering was my first exposure to the world to bioengineering and the reason why I wanted to study it more. It's great to know that it's possible to generate tissue that can be utilized for healing purposes, because it's obvious that removing other healthy parts of the body to replace injured portion can be very painful. This not only true for skin grafts, but also to bone tissue as I learned from my article. Engineered tissue is definitely a great alternative to such painful procedures.
David and Angela,
It's great that both of you were attracted to bioengineering because of the advancements made in skin tissue engineering. Indeed there are more improvements that can be made, but the current capabilities of tissue-engineered skin do promise great things can be done in bioengineering.
Ben,
Most tissue-engineered skin used for grafts (depending on how serious the wound) are designed to incorporate into the body and stimulate the surrounding area to create new skin to replace the graft. So only the components necessary for encouraging the body's own wound healing processes are found including keratinocytes that are incorporated with the protein fibronectin. This induces production of keratin growth factor that helps with skin cell proliferation.
Fibroblasts are also found in engineered skin. In fact there are current studies showing that fibroblast made by cell-aggregates in combination with a biodegradable polymer (a scaffold for support) actually greatly improves the potential for wound healing.
Also the use of insulin, dexamethasone, basic fibroblast growth factor, and ascorbic acid have been known to be used in some tissue-engineered skin.
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