Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly.
Thymosin beta 4 has previously been found to promote dermal and corneal repair in normal rats. Here we report that
thymosin beta 4 was also active in accelerating
wound repair in full-thickness dermal
wounds in both db/db diabetic and aged mice. We found that
thymosin beta 4 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 beta 4 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 beta 4 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 beta 4 in PBS. The actin-binding domain of
thymosin beta 4 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 beta 4 is active for
wound repair in models of impaired healing and may have efficacy in chronic
wounds in humans.