A QUANTITATIVE ANALYSIS OF THE INFLUENCE OF THE SIZE OF THE DEFECT ON WOUND HEALING IN THE SKIN OF THE GUINEA PIG
Authors: Spain Kate C. , Loeb Leo 
Published: June 2004

1. The larger the wound, the more rapidly the tongue enlarges and the earlier the closure of the wound takes place. Larger wounds heal, therefore, more quickly than smaller wounds within the variations in the size of the wound chosen in our experiments.
2. Both outgrowing of the tongues and contraction of the wound are concerned in the closing of the wound. A marked contraction sets in in the period preceding the closing of the wound and continues over a longer period with gradually diminishing intensity. The contraction, therefore, sets in earlier in the larger wounds. The contraction is also absolutely greater in the larger wound.
3. During wound healing the mitoses increase first markedly in the old epithelium and only very few mitoses can be found in the outgrowing epithelium during the first two days. Very soon the mitotic proliferation extends to the tongue and the number of proliferating cells may here become greater than in the old epithelium. With the closure of the wound a sudden fall in the number of mitoses takes place in both series. This fall is greatest in the tongue. Throughout the time of observation the number of mitoses is greater in the smaller wound. The fall in the number of mitoses directly after the closure of the wound is more sudden in the 4 mm. than in the 2 mm. series. It is, however, possible that the increase of mitoses extends over a larger area in the 4 mm. series than in the 2 mm. series.
4. It is probable that the difference in the rapidity in the outgrowth of the epidermal tongues and the resulting difference in the time of closure are mainly responsible for the difference in the variations in mitoses in the larger and smaller wounds. The longer the period of time over which the pull of the epithelium extends, the greater is the number of mitoses in this area. Therefore it is greater in the 2 mm. series. Closure of the wound is followed by a sudden decline in the number of mitoses especially in the area of the defect. Therefore the number of mitoses decreases earlier in the 4 mm. series, and we find here the smallest number of mitoses during the whole period of our observation.
5. The size of the epithelial cell and nucleus increases soon after the making of the wound. A maximum is reached in both the larger and smaller wound in the period just preceding the closure of the wound; this maximum is therefore reached earlier in the larger wound. Absolutely the maximal size reached in both kinds of wounds is approximately the same or only a little higher in the larger wounds. After the closure of the wound a sudden decline in the cell size takes place in the larger as well as in the smaller wounds. Then a more gradual decline sets in. Fourteen days after the operation the cells are still larger than in the normal skin. The variations in the size of the nucleus are similar to those in the whole cell, but less marked. The curves of variations in cell and nuclear size follow in both the larger and smaller wounds a curve similar to the variations in the number of mitoses. But the cell size returns more slowly to the normal condition than the number of mitoses.
6. The closure of the wound causes an increase in the number of epithelial rows over the defect. This increase is therefore reached at an earlier period in the larger wound. The increase is greater in the larger wound owing to the greater pressure which the two opposing cell layers exert upon each other in the larger wound. In the old epithelium the maximum in the number of cell rows is apparently reached slightly before the closure of the wounds. It seems that the epithelial movements leading to the closure of the wound start in the old epithelium and extend wave-like towards the wound.
7. It thus appears that the primary process in the wound healing consists in movements of the epidermis towards the wound, that these movements are carried out with greater energy in the case of the larger wounds, that the pull of the epithelium calls forth mitotic cell division, and that pressure exerted by epithelial cells upon each other leads to a rapid diminution in the mitotic proliferation.