Lower Metal Element Levels in Hypertrophic Scars: A Potential Mechanism of Aberrant Cicatrix Hyperplasia

BACKGROUND: We investigated levels of the metal elements Ca, Mg, Zn, Fe, and Cu in blood, normal skin (NS), and different types of scar tissue and aimed to elucidate the pathogenesis of hypertrophic scars (HS). MATERIAL/METHODS: Tissue specimens were excised from 3 groups of research participants: scar-free, flat scar (FS), and HS groups. Levels of the study elements were measured in blood, NS, and scar tissues with a spectrophotometer. The levels in plasma or in different types of specimens were compared among subgroups. In the FS and HS groups, levels were compared between the scar tissue and NS of each individual. In addition, element differences in exposed and unexposed areas of NS were investigated in the scar-free group. HS fibroblasts (HFB) were cultured in medium with various reduced levels of metal elements to determine the influence of metal elements on fibroblast growth. RESULTS: Levels of trace elements, including Zn, Fe, and Cu, were significantly lower in HS than in FS. The levels of Ca, Zn, Fe, and Cu were markedly lower in HS than in the patients’ own NS, while the Cu/Zn ratio was higher. However, no such difference was observed in the FS group. No significant difference in element levels was found in either plasma or NS among the 3 groups. Reduced levels of the elements promoted HFB proliferation within 24 h while an inhibition effect was observed at 72 h. CONCLUSIONS: Our findings indicate reduced levels of metal elements in part of the healing microenvironment, suggesting that decreased metal levels may be involved in the pathogenesis of HS.