SKIN AND WOUND HEALING
5 me factors aff cti g skin
a
Gund ealing
GO Winter
Department of Biomechanical Engineering, The Institute Hospital, Stanmore, Middlesex
of Orthopaedics, Royal National Orthopaedic
This article first appeared in Bedsore Biomechanics and is reproduced by kind permission of Palgrave Macmillan, Macmillan Publishers Ltd
Summary The domestic pig is the preferred animal for studying the effects of environmental factors on skin and wound because its integument is more like that of man than any other, The three factors that most drastically affect the pattern, speed and quality of healing are dehydration of exposed tissues, the status of the blood supply bringing oxygen and nutrients to the area and sepsis, Wounds exposed to the air lose water vapour, the upper dermis dries and healing takes place beneath a dry scab, Covering a wound with an occlusive dressing prevents scab formation and radically alters the pattern of epidermal wound healing. Blowing on wounds creates a scab within three hours instead of the normal 24 hours but more tissue is sacrificed in the process. This may only b' justified if it can be shown that rapid artificial scab formation significantly cuts down the incidence of severe infections, i.e. in large burns. Less serious wounds heal faster when covered with a suitable occlusive dressing. Indolent wounds are characterised by a rim of infected, necrotic tissue in which leucocytes and macrophages are unable to function effectively through lack of oxygen. A suitable dressing changed frequently can bring about mild debridement and re-establish the conditions for healing.
epidermis is not ridged and is very thin. In pig and man, which have a mere 40-60 hairs per cm 2, the follicles are up to 2.0mm apart and there is relatively much more surface epidermis which is thicker and less permeable. The more robust epidermis of these species is attached to the dermis by a continuous system of ridges formed by thickened epidermal tissue. In consequence the dermis displays two distinct regions, a deeper reticular layer of relatively coarse fibres and a more compact superficial layer with papillae. The existence of dermal papillae interdigitating with the epid'rmis imposes a regular pattern on the terminal blood V"S 'els in the surface of the skin. In hairy animals insulation against cold is provided by a layer of still air trapped in the fur external to the skin.
FIGURE 1
PIG SKIN
Epidermis
Dermis
Skin characteristics in pig and man There is no animal with skin exactly like that of man but for investigations of cutaneous biology the pig is often the most apt experimental animal (figure I). The Large White or Yorkshire breed has a sparse coat of hair. Other pigs, among them the European wild pig, the Pitman Moore miniature pig and some domestic breeds have coarser skins and a thicker pe13ge. In a furry animal there may be 3,000-4,000 hairs per cm 2 (Tregear, 1966) which are only fractions of a millimetre apart and consequently follicle pores occupy a significant proportion of the surface. The high density of epidermal il1\'aginations adequately attaches the epidermis to the dermis and the interfollicular
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Hypodermis
Muscle of body wall
Low power photomicrograph of skin from the
back of a young Large White pig
VOL 16 NO.2 MAY 2006
In near-naked species like man and pig the insulant is fat under the dermis. Heat is conserved by lowering th skin circulation and allowin the dermis to cool beloyv core temperature. In man and the pig the skin is firmly attached to underlying tissues and not nearly as mobile as in, for example, the rabbit or dog. Thus in basic anatomy the skin on the back of a young Large White pig is similar to that of human adult skin on th back or thigh. These common features are mainly a consequence of their near-hairlessness. There are regional variations as in the epidermis of the pig's snout or sole of foot. The most striking differences between porcine and human skin are in adaptations to hot environments. Unlike man, the pig does not sweat over the general body surface (Ingram, 1964). There arc numerous apocrine glands associated with hair follicles but no eccrine glands except on the snout.
FIGURE 2 UPPER DERMIS OF A FIVE·DAY-GLD SHALLOW WOUND
Logistics of wound healing In the healing of a shallow wound in porcine skin, 6.25cm 2 in area, over 90 per cent of the new epidermis originates from hair follicles involved in the wound (Winter, 1971). Hair follicles (and other epidermal downgrowths in the dermis) perform a vital service as reservoirs of epidermal cells capable of migrating across a wound and building a new surface:layer. Epithelisation is more rapid in hairy species like the rabbit than less hirsute ones like man and the pig. In anyone individual the areas of the body plentifully supplied with epidermal appendages heal more rapidly than those less well endowed. Epidermal wound healing is faster in children than in adults for the good reason that hair follicles do not increase in numbers as the body grows, and as surface area. expands they become further apart. Migrating epidermal cells move at about one cell diameter an hour (Winter, 1972) and it takes seven days to bridge the gap from one hair follicle to the next in man and pig. The logistics of dermal wound healing are similar. The sources of new tissue are not, as might be thought, the resident cells of the tissue, the dermal fibrocytes, but cells of loose connective tissue in the perivascular compartments (Figure 2). For this reason the pattern of blood vessels influences the pattern of repair. A very shallow wound in the skin of pig or man heals almost perfectly because the basic vascular pattern survives the injury, but deep wounds heal imperfectly because nothing is left of the original vascular architecture. Wound contraction in very loose skin obliterates most of the repair tissue which is an ephemeral organ of repair (Billingham and Medawar, 1955) but in the less mobile skin characteristic of pig and man extensive permanent scar tissue is formed.
VOL 16 NO.2 MAY 2006
Sagittal section through the upper dermis of a five-day
old shallow wound showing the vascular compartments
which are the sources of new tissue
The influence of environmental factors We have used young Large White pigs to study the effects of some environmental factors on healing. Up to 12 wounds may be studied in each animal and these can be adequately protected against accidental damage (Winter and Clarke, 1971). Histological studies show that destruction of the epidermal barrier exposes the dermis to dehydration. A scab forms which consists of coagulated dried blood, serous exudate, inflammatory cells and some of the exposed dermal tissue (Figure 3). When epidermal regeneration begins, about 18 hours after the original insult to the skin, the epidermal cells move below the scab through dermal tissue (Winter, 1962). Similar events take place at the surface of shallow wounds, d ep wounds, incisions and burns. It ilppears that the greatest influence we milY exert on healing is to cover the wound surfaces, so preventing dehydration and scab formation. Under a suitable occlusive dressing the epidermis moves over the original wound surface through a moist exudate between the dressing and the wound (Figure 4) about three times faster than it moves below a scab (Winter, 1962, 1964; Hinman et ai, 1963; Rovee and Miller, 1968; Bothwell and Rovee, 1971). A very superficial injury will normally heal perfectly, as mentioned above. If through damage caused by dehydration and scab formation the papillary rete of blood vessels lying near the surface is destroyed that
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SKIN AND WOUND HEALING
FIGURE 3 EDGE OF SHALLOW WOUND THREE DAYS OLD
Edge of shallow wound three days old, showing scab
formation and level of epidermal migration
same wound will heal by granulation tissu with scarring. Again, if a deep partial thickness lO.lury contains .living epidermal elements it will heal spontanecrusly.
FIGURE 4
SHALLOW WOUND TWO DAYS OLD
Dressing
Moist exudate Epidermis
Wound
surface
Part of shallow wound two days old, showing polyurethane foam dressing, absence of scab and migration of epidermis through fluid exudates above the wound surface
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If these sources of epidermis are destroyed by secondary damage caused by dryi.ng, the wound will not heal at all and will need "rafting. Thus in wound management it is important to maintain hydration of the tissue and preserve the exposed tissue elements. It is no use, for example, excising burns or debriding ulcers and then letting the newly exposed tissue die through dehydration. Another factor of major significance for wound healing is the prevailing oxygen tension. Wou~1d surfaces are normally relatively anoxic (Hunt and Zederfeldt, 1969; Silver, 1972; Niinikoski and Kivisaari, 1973) because of damage to the blood supply and stasis in the extracellular fluid compartment. Particularly does this apply to the peripheral zone of burns and pressure sores. Another factor that reduces the amount of oxygen available for regenerative activities is its rapid utilisation by inflammatory cells which are present in very large numbers in a chronic infected wound. In our experiments, covering wounds with films of low oxygen permeability delayed pithelisation (Winter, 1972). The most rapid epidermal healing was recorded when animals were treated in a hyperbaric oxygen chamber (Winter and Perrins, 1970). Covering wounds with ointments is equivalent to using an occlusive dressing. Some ointments may hecome incorporated into the wound and cause undesirable tissue reactions (Simpson and Winter, 1971). Further research is required into the most suitable formulations with optimum gaseous permeabilities and cohesive properties. The opposite technique to occluding wounds is to blow a current of air over them. This produces a deeper scab more rapidly (Figure 5), involves death of more tissue and delays epithelisation (Winter and Scales, 1963). The only justification for this may be to protect the tissues from secondary infection and to control fluid loss in severe burns (Scales and Winter, 19 4).
Indolent wounds When dealing with indolent wounds bordered by a zone of infected, n erotic tissue treatment is directed towards re-establishing a suitable environment for epithelisation and connective tissu regeneration. From what has been said already it may be deduced that the minimum requirements are a moist protein rich medium into which the cells can move and a supply of oxygen and glucose molecules. A first priority is to remove the primary cause of the trouble which will usually be ahnormal local pressure which has shut off the blood supply to the affected area. This in itself may be sufficient to initiate healing but more drastic measures may be needed. Leucocytes can still ingest bacteria in conJitions of hypoxia but cannot kill them. Macrophages, which are
VOL 16 NO.2 MAY 2006
avid users of oxygen, are required to clear away the debris. Fibroblasts cannot function efficiently at low oxygen tensions (Hunt and Zederfeldt, 1969). Success in treating burns and infected sores, r istant to other forms of treatment, has followed the use of clay packed into the wound (Kamp and Watts, 1967). More recently, good results have been achieved using a dressing (Lyofoam) having a hydrophilic microporous surface membrane with a hydrophobic, cavity-linked cellular structure on the outside. The dressing is changed two or three times a day for the first five days but thereafter less frequently. In the initial period the necrotic tissue becomes macerated and the wound looks very messy but about the sixth day tl1e wound clears dramatically. The probable explanation for these events is that the dressing maintains a moist atmosphere at the tissue surface and allows diffusion of oxygen while preventing reinfection, thus providing favourable conditions for the leucocytes and macrophages to cleanse the wound. The cleaning process is aided by the frequent removal of dressing and adhering tissue breakdown products. Other methods of debridement include the use of proprietary proteolytic enzyme preparations including collagenases. An essential part of any such therapy is to protect the wound surface from dehydration.
References Billingham RE, Meda,var PB. (1955) Contracture and intussusc ptive growth in the healing of extl'nsive wounds in mammalian skin. Anar Land 89: 114-23. Bothwell JW, Rovee I 'L (1971) The efFe of dressings on the repair of cutan ous wounds in humans. In: Surgical Dressings and Wound Healil1g (ed. Harkiss K.I). Bradford University Press, 78-97. Hinman CD, Maibach HI, Winter GD. (1963) Effect of air exposure and occlusion on experimental human skin wounds. Narure Land 200: 377-79. Hunt TK, Zederfeldt MD. (19G9) Nutritional and environmental aspects of wound healing. In: Repair and Regenemrion (eds. Dunphy .IE, Van Winkle HW). New York: McGraw-Hill, 217 -28. Ingram DL. (1964) The effect of environmental temperature on heat loss and thermal insulation in the young pig. Res Vet Sci 5: 357-64. Kamp HF, Watts Jc. (1967) Progr ssive debridement with control of insensible water loss in burns using a coLioidalsilicate dressing. A clinical observation. S Afr Med ] 41: 651-55. Niinikoski J, Kivisaari J. (1973) Oxygen and wound healing. In: Biology of Fibroblast (eds. Kulonen E, Pikkarainen 1). London: Academic Press, 591-99. Rovee DT, Miller CA. (1968) Epidermal role in the breaking ·trength of wounds. Archs Surg 96: 43-52. Scales JT, Winter GD. (1964) 'Leviration'. A Possible Means of Treating Bums. Paris: I.a Cicatrisation Editions du Centre National de la Recherc.he Sciencifique, 1-10. Silver IA. (1972) Oxygen t nsion and epithelization. In: Epidermal Wound Healing (cds. Maibach HI, Rovee DT). Chicago: Year Book Medical Publishers, 291-305. Simpson BJ, Winter GD. (1971) A method of studying the performance of dressings using a standard wound in the domestic pig. In: Surf(ical Dressings and Wound Healing (ed.
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FIGURE 5
WOUND THREE DAYS OLD
Dried exudate
Dermal fibrous tissue
Leucocytes
Level of epidermic migration
Hydrated dermis
Part of surface of wound three days old, showing thick scab caused by extensive drying. Air at 40°C was blown over the fresh wound surface at 0.637m J jsec for one hour
Harkiss KJ). Bradford University Press, 70-77. Trcgear RT. (1966) Physical Functions of Skin. London: Academic Press. Winter GD. (1962) Formation of th' scab and the rate of epithelisation of superficial wound. in the skin of the young domestic pig. Narure Lond 193: 293-94. Winter GO. (1964) Movement of epidermal cells over the wound surface. In: Advmu:es in Biology of Skin. S, Wound Healing (eds. Montagna W, Billingham RE). Oxford: Pergamon Press, 113-27. Winter GO. (197 I) Healing of skin wounds and the influence of dressings on the repair proc ss. In: Surgical Dressings and YVtmnd Healing (ed. Harkis. KJ). Bradford University Press, 46-60. Winter GD. (1972) Epidermal regeneration studied in the dom'stic pig. In: Epidemlal Wound Healing (cds. Maiback ~Il, Rove DT). Chicago: Year Book Medical Puhlishers, 71 112. Wiater GD, Clarke DW. (l971) The pig as a laboratory animal for the study of wound healing and surgical dressings. In: Surgical Dressings and Wound Healing (ed. Harkiss KJ). Bradford University Press, 61-69. Winter GD, Perrins DJ. (1970) Effects of hyperbaric oxygen treatment on epidermal regeneration. In: Proceedings oj the 4th lnternational Congress on Hyperbaric Medicine. (eds. Wada J, Iwa T). Tokyo: Igaku Shoin, 363-68. Winter GD, Scales JT. (1963) Effect of air drying and dressings on the surface of a wound. Nature Land 197: 91-92.
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