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SKIN GRAFTS AND SKIN SUBSTITUTES
James F Thornton MD
HISTORY OF SKIN GRAFTS ANATOMY
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Ratner and Hauben and colleagues give excel- The character of the skin varies greatly among
lent overviews of the history of skin grafting. The individuals, and within each person it varies with
following highlights are excerpted from these two age, sun exposure, and area of the body. For the
sources. first decade of life the skin is quite thin, but from
Grafting of skin originated among the tilemaker age 10 to 35 it thickens progressively. At some
1 point during the fourth decade the thickening stops
caste in India approximately 3000 years ago. A
common practice then was to punish a thief or and the skin once again begins to decrease in sub-
adulterer by amputating the nose, and surgeons of stance. From that time until the person dies there is
their day took free grafts from the gluteal area to gradual thinning of dermis, decreased skin elastic-
repair the deformity. From this modest beginning, ity, and progressive loss of sebaceous gland con-
skin grafting evolved into one of the basic clinical tent.
tools in plastic surgery. The skin also varies greatly with body area. Skin
In 1804 an Italian surgeon named Boronio suc- from the eyelid, postauricular and supraclavicular
cessfully autografted a full-thickness skin graft on a areas, medial thigh, and upper extremity is thin,
sheep. Sir Astley Cooper grafted a full-thickness whereas skin from the back, buttocks, palms of the
piece of skin from a man’s amputated thumb onto hands and soles of the feet is much thicker.
the stump for coverage. Bunger in 1823 success- Approximately 95% of the skin is dermis and the
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fully reconstructed a nose with a skin graft. In 1869 other 5% is epidermis. The dermis contains seba-
Reverdin rekinkled worldwide interest in skin graft- ceous glands and the subcutaneous fat beneath the
ing with his report of successful pinch grafts. Ollier dermis contains sweat glands and hair follicles. The
in 1872 pointed out the importance of the dermis skin vasculature is superficial to the superficial fas-
in skin grafts, and in 1886 Thiersch used thin split- cia and parallels the skin surface. The cutaneous
thickness skin to cover large wounds. To this day vessels branch at right angles to penetrate subcuta-
the names Ollier and Thiersch are synonymous with neous tissue and arborize in the dermis. The final
thin (0.005–0.01-inch) split-thickness grafts. destination of these blood vessels is a capillary tuft
Lawson, Le Fort, and Wolfe used full-thickness that terminates between the dermal papillae.
grafts to successfully treat ectropion of the lower
eyelid; nevertheless, it is Wolfe whose name is TERMINOLOGY
generally associated with the concept of full-
thickness skin grafting. Krause popularized the use An autograft is a graft taken from one part of an
of full-thickness grafts in 1893, known today as individual’s body that is transferred to a different
Wolfe-Krause grafts. part of the body of that same individual. An isograft
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Brown and McDowell reported using thick split- is a graft from genetically identical donor and
thickness grafts (0.01–0.022-inch) for the treatment recipient individuals, such as litter mates of inbred
of burns in 1942. rats or identical human twins. An allograft (previ-
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In 1964 Tanner, Vandeput, and Olley gave us ously homograft) is taken from another individual of
the technology to expand skin grafts with a machine the same species. A xenograft (heterograft) is a
that would cut the graft into a lattice pattern, graft taken from an individual of one species that is
expanding it up to 12X its original surface area. grafted onto an individual of a different species.
In 1975 epithelial skin culture technology was A split-thickness skin graft (STSG) contains epi-
5 dermis and a variable amount of dermis. A full-
published by Rheinwald and Green, and in 1979
cultured human keratinocytes were grown to form thickness skin graft (FTSG) includes all of the der-
6 8
an epithelial layer adequate for grafting wounds. mis as well as the epidermis (Fig 1). The donor site
SRPS Volume 10, Number 1
Fig 1. Split-thickness skin grafts include a variable
amount of dermis. Full-thickness grafts are taken
with all the dermis. (Reprinted with permission
from Grabb WC: Basic Techniques of Plastic
Surgery. In: Grabb WC and Smith JW: Plastic
Surgery, 3rd Ed. Boston, Little Brown, 1979.)
of an FTSG must be closed by either direct suture can also be described as a general adaptation of
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approximation or skin graft. connective tissue to a diminished blood supply.
EPIDERMIS
PROPERTIES OF SKIN GRAFTS In the mid-1940s Medawar studied the behavior
Skin grafts have been used for over a century to 12–14
and fate of healing skin autografts. His findings
resurface superficial defects of many kinds. can be summarized as follows.
Whether intended for temporary or permanent
cover, the transplanted skin does not only protect Histologic Aspects
the host bed from further trauma, but also provides
an important barrier to infection. During the first 4 days postgraft there is tremen-
Thin split-thickness skin grafts have the best “take” dous activity in the graft epithelium, which doubles
and can be used under unfavorable conditions that in thickness and shows crusting and scaling of the
would spell failure for thicker split-skin grafts or full- graft surface. Three cellular processes may explain
thickness grafts. Thin STSGs tend to shrink consid- this thickening: 1) swelling of the nuclei and cyto-
erably, pigment abnormally, and are susceptible to plasm of epithelial cells; 2) epithelial cell migra-
trauma.9 In contrast, full-thickness grafts require a tion toward the surface of the graft; and 3) accel-
9 10
well-vascularized recipient bed until graft perfu- erated mitosis of follicular and glandular cells. By
sion has been reestablished. FTSGs contract less the third day after grafting there is considerable
upon healing, resist trauma better, and generally mitotic activity in the epidermis of a split-thickness
look more natural after healing than STSGs. skin graft, whereas mitotic activity in full-thickness
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Rudolph and Klein review the biologic events skin grafts is much less common and may be totally
that take place in a skin graft and its bed. An absent—a reflection of their less-efficient early cir-
ungrafted wound bed is essentially a healing wound culation.
which, left alone, will undergo the typical processes Between the fourth and eighth days after graft-
of granulation, contraction, and reepithelialization ing there is great proliferation and thickening of the
to seal its surface. When a skin graft is placed on a graft epithelium associated with obvious desqua-
wound bed, these processes are altered by the pres- mation. Epithelial thickness may increase up to
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ence of the graft. sevenfold, with rapid cellular turnover. At the same
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Marckmann studied biochemical changes in a time the surface layer of epithelium exfoliates and
skin graft after placement on a wound bed and is replaced by upwardly migrating cells of follicular
noted similarities with normal skin in its response to epithelium at an accelerated rate. This heightened
physical or chemical injury and aging. The changes mitosis does not begin to regress until after the first
in wound healing brought about by the skin graft week postgrafting. By the end of the fourth week
2
SRPS Volume 10, Number 1
postgraft the epidermal thickness has returned to its hand, concluded that split-thickness and full-
normal, pregraft state. thickness skin autografts undergo considerable col-
lagen turnover. In their experiments the dermal
Histochemical Aspects collagen became hyalinized by the third or fourth
day postgraft, and by the seventh day all of the
The RNA content of graft epithelial cells changes collagen was replaced by new small fibers. The
15 By the fourth
little in the first few days postgraft. replacement continued through the 21st postgraft
day postgraft RNA content increases greatly in the day, and by the end of the sixth week postgraft all
basal layers of epithelium, paralleling the hyperac- the old dermal collagen had been completely
tivity of epithelial cells caused by acceleration of replaced. The rates of collagen turnover and epi-
protein synthesis during a period of rapid cellular thelial hyperplasia peaked simultaneously in the first
replication. By the 10th day postgraft the RNA 2–3 weeks postgraft.
level returns to normal.15 21,22 23
Klein and Peacock used hydroxyproline to
Over the first 2 to 3 days enzymatic activity pro- determine the collagen content of grafted wounds.
gressively decreases in split-thickness skin grafts, Hydroxyproline is an amino acid found exclusively
but as new blood vessels enter the dermis–epidermis in collagen at a constant proportion of 14%.
junction, the enzyme levels rebound. Changes in hydroxyproline and monosaccharide
content of grafted beds paralleled those of other
24 25
DERMIS healing wounds. Independent studies by Hilgert
26
and Marckmann confirmed these findings and
Cellular component documented plunging levels of hydroxyproline soon
The source of fibroblasts in a skin graft remains after grafting. The hydroxyproline (collagen) level
16 eventually rebounded and finally returned to the
obscure. Early investigators believed that these normal levels of unwounded skin. Although Hilgert’s
cells came from large mononuclear cells in the blood,
17 cycle lasted 10 days and Marckmann’s 14–21 days,
while Grillo theorized that they originated from
local perivascular mesenchymal cells. Whatever it is now well established that most of the collagen
their origin, most authors are convinced that active in a graft is ultimately replaced.
fibroblasts in a healing skin graft do not come from On the basis of studies involving tritiated pro-
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indigenous fibrocytes. line-labeled mature collagen, Udenfriend and
18 Rudolph and Klein28 agreed that 85% of the origi-
Converse and Ballantyne studied cell viability in nal collagen in a graft is replaced within 5 months
rat skin grafts by assaying levels of diphosphopyri- postgraft. The collagen turnover rate of grafts is 3X
dine nucleotide diaphorase, an indicator of active
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electron transport. The authors noted falling fibro- to 4X faster than that of unwounded skin. In addi-
cyte numbers in the first 3 days after grafting. The tion, although equal amounts of collagen are lost
remaining fibrocytes lay in two narrow layers, one from full- and split-thickness grafts, STSGs replace
beneath the dermis–epidermis junction and the other only half as much of their original collagen as do
just above the host bed. After day 3 fibroblast-like FTSGs of equal size.
cells began to appear, first in the graft bed and later Elastin fibers in the dermis account for the
in the graft itself. By the seventh to eighth day resilience of skin. While the elastin content of
postgraft the fibroblast population and enzymatic the dermis is small, the elastin turnover rate in a
activity were greater than in normal skin. After this healing graft is considerable, and most of the elas-
early burst in fibroblastic activity, however, both tin in a graft is replaced within a short time. Elas-
fibroblast numbers and enzyme levels resumed their tin fiber integrity is maintained through the third
normal, pregraft states over the ensuing weeks. postgraft day, but by postgraft day 7 the fibers are
19
short, stubby, and have begun to fragment. Elas-
Fibrous component tin degeneration continues through the third
postgraft week until new fibers can be seen
12,13 stated that most of the collagen in beginning to grow at 4–6 weeks postgraft. This
Medawar
an autograft persists through the 40th day after graft- replacement process is the same in full- and split-
ing. Hinshaw, Miller, and Cramer,19,20 on the other thickness skin grafts.
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