Thymosin β4 and a synthetic peptide containing its actin‐binding domain promote dermal wound repair in db/db diabetic mice and in aged mice

Abstract

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. Thymosin β₄ has previously been found to promote dermal and corneal repair in normal rats. Here we report that thymosin β₄ was also active in accelerating wound repair in full-thickness dermal wounds in both db/db diabetic and aged mice. We found that thymosin β₄ in either phosphate-buffered saline or a hydrogel formulation is active in promoting dermal wound repair in normal rats. In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin β₄ in either phosphate buffered saline solution or a hydrogel formulation. No difference was observed in keratinocyte migration, with all of the diabetic animals showing almost complete coverage of the wound at 8 days. Wound healing in 26-month-old (aged) animals was significantly delayed. Thymosin β₄ accelerated wound healing in these aged mice, with increases in keratinocyte migration, wound contracture, and collagen deposition. The hydrogel formulation generally showed similar wound healing activity with thymosin β₄ in PBS. The actin-binding domain of thymosin β₄ duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in the aged animals comparable to that observed with the parent molecule. These studies show that thymosin β₄ is active for wound repair in models of impaired healing and may have efficacy in chronic wounds in humans. (WOUND REP REG 2003;11:19–24)