Pathologic scar formation. Morphologic and biochemical correlates

Abstract

Morphologic and biochemical analyses were performed to compare normal skin and mature scars to hypertrophic scar and keloid. Correlation of morphologic findings with biochemical profiles of the skin and scar samples proved feasible and enlightening. Scanning electron microscopy (SEM) was used to characterize the architectural arrangement of collagen fibers in skin and scars. Cultured fibroblasts from each specimen were also examined with the SEM. A biochemical profile of each tissue specimen was constructed, characterizing the collagen component of the specimen by sequential molecular sieve and ion exchange chromatography to determine a) the degree of intermolecular crosslinking, b) amino acid analysis, and c) levels of lysyl oxidase activity. Results indicate that collagen fibers and fiber bundles display a decreasing level of organization as the clinical degree of scar abnormality increases, and this structural gradient correlates with the gradient of intermolecular crosslinking in the same tissue--normal skin and mature scar being highly crosslinked, hypertrophic and keloid successively less so. Surprisingly, the level of the crosslinking enzyme lysyl oxidase is normal or elevated in hypertrophic scar and keloid despite the relative lack of crosslinking. Amino acid content was uniform for all specimens. Scanning electron microscopy examination of cultured fibroblasts from the tissue specimens demonstrated three phenotypically distinctive fibroblasts whose numerical and volumetric proportions correlated with the tissue of origin.