193293a0Nature1934812196201202932940028-0836196210.1038/193293a0ukNatureNatureNATUREnatureNature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public./nature/journal/v193/n4812issueJournal homeArchiveCurrent issueAdvance online publicationPrivacy policySubscribeNature Publishing GroupCurrent issue193293a0Formation of the Scab and the Rate of Epithelization of Superficial Wounds in the Skin of the Young Domestic Pig
AU  - WINTER, GEORGE D.Department of Biomechanics and Surgical Materials, Institute of Orthopaedics (University of London), Stanmore, Middlesex.WHERE there is a superficial wound in the skin, new epidermis covers the denuded area by migration from the hair follicles and sweat gland ducts within the wound and from the surface epidermis at the wound edges. It has been found that epithelization is retarded by the dry scab which normally covers a superficial wound, and if the formation of the scab is prevented, the rate of epithelization is markedly increased.These observations are derived from investigations on wound healing in the skin of pedigree Large White pigs 12-14 weeks old, fed on a standard diet without antibiotic. The experimental wounds were made with a sharp scalpel under surgically clean conditions. The wounds were 2-5 cm. square and 0-01-0-03 cm. deep. All surface epidermis and the papillary layer of the dermis were removed. Wounds were protected by a cage worn on the pig's back, so that no accidental damage was done to them.
To study the effects of keeping the wound surface moist, wounds were covered with polythene film. In all experiments control wounds were made on the same animal and were left exposed to the air.
The total area of regenerated epidermis on each wound was estimated from serial sections. Every fifth section in a series cut at 10(j. was examined at x 80 magnification and the separate lengths of regenerated epidermis and the total lengths of the sections were measured to within 0-01 mm.
The results of one such experiment are presented in Table 1. This experiment suggested that moist wounds were epithelialized more rapidly than dry wounds. To confirm this suggestion, the experiment was repeated on a second pig, taking biopsy speci mens from all the wounds at three days (Table 2). There was only about half as much new epidermis under the normal dry scab as under the polythene film. The difference is statistically highly significant (Table 3).
The conclusion from these experiments is that when superficial wounds in the skin of young domestic pigs are kept moist under cover of a relatively inert and impermeable film, epithelization of the denuded surface is about twice as rapid as on wounds exposed to the air.
Table 1. EPITHELIZATION UNDER NORMAL (DRY) AND EXPERIMENTAL (MOIST) CONDITIONS
Total length Total length of Time ~........ ' '
Wound
Dry Wounds 1 day 1
3 days 7
5 days 3
7 days 9
Mol"t wounds 1 day 2
8 days 8 5 days 4
of epidermis (mm. x 10~2)
1.608 26,212 55.524 77,902
section examined (mm. x 10-[ast])
71,479 77,001 77,504 78,075
Also at 9 and 11 days
Percentage of epidermis
34
72 100 100
11,827 64,495 18
77,598 78,904 98
71,721 71,721 100
Also at 7, 9 and 11 days 100
Pig 43. Superficial wounds, 2-5 cm.a. Skin depilated with wax 3 days before wound making. 6 wounds, no dressing (dry), 6 wounds covered with polythene film (moist), spaced alternately. Serial sections at 10//3 every fifth section measured.
Table 2. EPITHELIZATION UNDER NORMAL (DRY) AND EXPERIMENTAL (MOIST) CONDITIONS 
Total length Time Wound of epidermis
Dry wounds 3 days
3 5 6
8
9
12
Total (6 wounds)
Moist wounds 3 days 1
2
4 7
10 11
(mm. x 10~2)
59,481 32,940 23,224 24,892 23 232 30,254
194,023
Total length of
section examined Percentage of (mm. x 10-2) epidermis
83,804
87,120
106,804
101,362
78,045
71,557
Total (6 wounds) 528,692
102,865 81,635 70,050 66,119 65,183 90,756
476,608
84,410
87,120
106,902
101,574
79,089
76,434
535,529
58 40 33 38 36
J[ast]L
41 (40-7)
100 100 100
99
94
"9T (98-7)
Pig 47. Superficial wounds, 2-5 cm.2. Hair was clipped short immediately before wound making. 6 wounds, no dressing (dry), 6 wounds covered with polythene film (moist), distributed at random. Serial sections at lO^u, every fifth section measured.
Table 3. T TEST OF SIGNIFICANCE, DIFFERENCE BETWEEN DRY AND MOIST WOUNDS, DATA AS IN TABLE 2
Total length of epidermis
dry moist
32-6 88-1
14-1 13-6
t
6-970
P < 0-001
The explanation for this large difference in the rate of epithelization can be deduced from the histology of the wounds. Normally, when no dressing is used, and the wound is freely exposed to the air, the wound is covered by a dry, serous scab within 24 hr. Within the dermis under the wound, extravasated polymorphonuclear leucocytes migrate upwards and accumulate within the fibrous tissue immediately below the wound surface. Migration of epidermis from hair follicles and the wound edges has just begun at 24 hr. The moving sheet of epidermal cells passes through the fibrous tissue below the leuco-cytic layer. Therefore a superficial layer of the fibrous tissue of the dermis is included in the scab, and the original wound surface lies within the scab above the new epidermis. On the other hand, when the wound is kept moist under a polythene film, epidermis migrates through the serous exudate on the wound surface above the fibrous tissue of the dermis. A normal scab including fibrous tissue is not formed, and leucocytes migrate out of the dermis into the exudate. In contrast to the normal dry wound, the original wound surface is below the new epidermis.
From the experiments described, it appears that where there is a superficial wroun,d in the skin a part of the dermis is dehydrated by exposure. The regenerating epidermis migrates along the outermost level, which is sufficiently moist for the life of the cells, below the dehydrated layer of the dermis. Leucocytes are trapped at the surface of the dermis because they are unable to move through the dry tissue. The normal scab prevents the ingress of dirt and microorganisms and protects the delicate cells of the new epidermis from dehydration. It is formed, however, at the expense of some dermal tissue, and the rate of epidermal migration is less than the potential maximum. Migration is impeded by the bundles of collagen in the path of the epidermal cells.
It is interesting to inquire how the epidermis is able to pass through the fibrous bundles. There is no histological evidence that a layer of separation develops between the leucocytic layer and the underlying tissue. The fibres remain apparently intact between the dermis and the leucocytic layer up to the very edge of the advancing sheet of epidermis. Possibly the epidermal cells push through the collagen, the fibres being weakened by altered physical conditions at this level, or the collagen is dissolved locally by an enzyme secreted by the epidermal cells themselves, or by the leucocytes.
The demonstration that a simple change in physical conditions at the wound surface can have such a marked effect on the rate of epithelization has an important bearing on experimental methods in wound healing. It would be unwise to draw conclusions about the specific effects of various substances on the rate of w7ound healing, where the results may be complicated by occlusion of the wound, for example, by dressings or greasy bases. There is histological evidence, too, that the effects of keeping the wound surface moist extend beyond the phase of epithelization. The new connective tissue under the regenerated epidermis appears earlier than normal, suggesting that the stimulus for its production is linked with the presence of epidermis. It is hoped to report more fully on these observations in due course.
I wish to thank Dr. John T. Scales for making this work possible, Prof. W. S. Bullough for his advice and encouragement, Dr. A. McPherson for advice on the statistical analysis and Mrs. S. E. Barnett for assistance. The investigation is assisted by grants from the Medical Research Council and Messrs. Courtaulds, Ltd.