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SKIN GRAFTS and SKIN SUBSTITUTES James F Thornton MD

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SKIN GRAFTS and SKIN SUBSTITUTES James F Thornton MD SKIN GRAFTS AND SKIN SUBSTITUTES James F Thornton MD HISTORY OF SKIN GRAFTS ANATOMY Ratner1 and Hauben and colleagues2 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 caste in India approximately 3000 years ago.1 A point during the fourth decade the thickening stops 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 fully reconstructed a nose with a skin graft. In 1869 other 5% is epidermis.7 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 generally associated with the concept of full- TERMINOLOGY 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 Brown and McDowell3 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- In 1964 Tanner, Vandeput, and Olley4 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- published by Rheinwald and Green,5 and in 1979 dermis and a variable amount of dermis. A full- cultured human keratinocytes were grown to form thickness skin graft (FTSG) includes all of the der- an epithelial layer adequate for grafting wounds.6 mis as well as the epidermis8 (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 approximation or skin graft. connective tissue to a diminished blood supply.11 EPIDERMIS PROPERTIES OF SKIN GRAFTS In the mid-1940s Medawar studied the behavior Skin grafts have been used for over a century to and fate of healing skin autografts.12–14 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 the host bed from further trauma, but also provides Histologic Aspects 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- well-vascularized recipient bed9 until graft perfu- erated mitosis of follicular and glandular cells.10 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 Rudolph and Klein9 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 ence of the graft.10 sevenfold, with rapid cellular turnover. At the same Marckmann11 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 collagen became hyalinized by the third or fourth Histochemical Aspects 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 little in the first few days postgraft.15 By the fourth 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 Klein21,22 and Peacock23 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 and Marckmann26 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 obscure.16 Early investigators believed that these eventually rebounded and finally returned to the cells came from large mononuclear cells in the blood, normal levels of unwounded skin. Although Hilgert’s while Grillo17 theorized that they originated from cycle lasted 10 days and Marckmann’s 14–21 days, 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- indigenous fibrocytes.
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