Maturation of Granulation Tissue

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Abstract
To study the mechanisms involved in the resorption of collagen and the appearance of fat in maturing granulation tissue, steel wire mesh cylinders were implanted in skin folds on white rabbits. The tissue formed within the cylinders was removed after 3, 4, 5, 6 and 8 wk and investigated by means of EM and enzyme histochemisty. By light microscopy, an early production of collagen was found, which diminished from the 4th wk. At the 5th wk, blood vessels and macrophages appeared and the collagen density decreased sharply. Simultaneously, intense activity of diaphorases was observed. By EM, typical long narrow fibroblasts with a densely packed endoplasmatic reticulum were found. These cells had collagen fibers close to the cell walls. From the 4th wk on, a collagen-free zone with amorphous content was observed around the fibroblasts where at the same time the nucleus was displaced towards 1 of the poles and the cisterns in the endoplasmatic reticulum were widened. In some cells, fat inclusions were detected from the 5th week. Another kind of cell was observed at the same time which had a more rounded nucleus and fat inclusions varying from small droplets to large confluent aggregations. By ultrastructural enzyme histochemistry, lysosomal precipitations could be found in the fibroblasts around which collagen had disappeared. In cells with a rounded nucleus and fat inclusions, acid phosphatase activity was also observed. Evidently fibroblasts participated in the break down and resorption of collagen in maturing granulation tissue from the 4th wk with the help of lysosomal enzymes. This collagenolytic activity was at maximum at the 5th week and fat cells appeared in the tissue concomitantly. These fat cells were derived, at least partly, from macrophages.