Biomedical Engineering Reference
In-Depth Information
14 after application. In addition, the supply can be erratic and there is also a
possibility of bacterial or other disease transmission. Clearly better techniques
were needed to treat very large wounds more optimally.
1.2
Skin regeneration
An injured epidermis heals by spontaneous regeneration, leading to formation of
a new, intact epidermis. In contrast, the injured adult dermis generally does not
regenerate spontaneously and heals instead by wound contraction and scarring. A
superficial injury in the dermis may show restoration as described in an experimen-
tal incisional scar model in humans showing that incisions made at a depth of 0.53
mm or less (approximately the top one-third of the dermis) showed no long-term
visible scar.
3
In contrast, deep partial thickness burns, full-thickness burns and full-
thickness traumatic wounds heal exclusively with scarring and wound contraction.
In the late 1970s and 1980s three groups at the Massachusetts Institute of
Technology (MIT) worked independently on three different methods to treat the
skin substitute problem. The results of their research provide the foundation for
most skin substitute research done today. Howard Green, working with James
Rheinwald pioneered cell culture techniques including culturing of
keratinocytes.
4
Prior to their innovations, culturing keratinocytes was difficult.
Their contributions included specific culture media and the addition of irradi-
ated fibroblasts as a feeder layer for keratinocytes. From a small biopsy of
normal skin, taken shortly after the burn injury, they were able to grow rapidly
large quantities of keratinocyte sheets referred to as cultured epithelial autografts
(CEAs) which could be grafted onto the burn wound within three weeks. This
technique became famous when Gallico and O'Connor applied it to two se-
verely burned children at The Shriners Burns Institute in Boston who were able
to survive a massive burn injury.
5
At the time, there was a debate about whether
or not dermis was a necessary component for the long term success of the
technique. Despite the remarkable achievements of Gallico and O'Connor, oth-
ers found that using CEAs alone resulted in a very fragile skin. Cuono later
showed that applying allograft sheets first, and then removing just the epidermis
prior to the application of CEAs, resulted in more stable coverage.
6
This tech-
nology formed the basis for the company Advanced Tissue Sciences that was
later sold to Genzyme® Tissue Repair (Cambridge, Massachusetts). CEAs are
still an important adjunct in treating very large burns. Because the number of
large burns is decreasing in the USA, the market size for this technique has not
grown significantly in the last several years.
Eugene Bell developed a fibroblast seeded collagen lattice and then covered this
with keratinocytes.
7
The collagen lattice contracted significantly
in vitro
after
being seeded with keratinocytes. These lattices could then be covered with a
keratinocyte layer to perform a 'skin equivalent'. This technique never really
caught on in the burn community and now is most often used with allogenic cells
