Inhibition of tissue transglutaminase and ɛ (γ‐glutamyl) lysine cross‐linking in human hypertrophic scar

Immunohistochemical staining with monoclonal antibody to tissue transglutaminase was used to study cryostat sections of human skin wounds. The enzyme was found in acute wounds and chronic hypertrophic scars but not in normal mature scars. Because tissue transglutaminase is responsible for the formation of isopeptide cross-links, a two-stage high-performance liquid chromatographic analysis was used to quantitate the epsilon (gamma-glutamyl) lysine cross-link produced by various types of wound tissues. Eighteen patients with hypertrophic scars between 6 months' and 10 years' duration after injury underwent a double-blind trial with putrescine 50 mmol/L in a eutectic vehicle for 2 months under nonocclusive dressings (Biofill). For the control portion of the same or different scar, sham vehicle and non-occlusive dressing were simultaneously applied. Both scars were harvested at biopsy or elective revision surgery 2 months later. After homogenization and exhaustive proteolysis, digests were studied with the use of high-performance liquid chromatography analysis. The results of treatment were a significant decrease in the levels of isopeptide cross-link formation from 0.018 +/- .006 nmol/micromol amino acids in untreated scars to 0.008 +/- .001 nmol/micromol amino acid in the treated group (p < 0.05). The isopeptide cross-link content in treated scars was nearly as low as that in normal mature scars (0.003 +/- 0.001 nmol/micromol amino acid). These results show that cross-link formation by tissue transglutaminase activity is inhibited during treatment of hypertrophic scar by putrescine. These results support the possible therapeutic use of topical putrescine in the treatment of hypertrophic scar formation.