The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing.

Acute skin injuries can result in the breakdown of the skin barrier, heightening the risk of infections and complications. Histatin 1 (Hst1) promotes the adhesion, spreading, and migration of various skin-related cells, thus encouraging wound healing. However, Hst1 is extensively degraded upon exposure to wound exudates. Cyclized hst1 (Cyclic-hst1) has a much higher resistance to protease degradation than Hst1, thus increasing its stability and half-life. Herein, we synthesized Cyclic-hst1 via a click reaction and explored its efficacy in wound healing via cellular and animal experiments. Cyclic-hst1, at a 100-fold lower concentration than Hst1, effectively promoted acute skin wound healing. In addition, Cyclic-hst1 had a superior effect to Hst1 in terms of its anti-inflammatory, re-epithelialization, collagen deposition, and angiogenic effects, thus significantly promoting skin wound healing. Consequently, Cyclic-hst1 could represent a favorable treatment to manage acute skin wound healing, providing a promising experimental basis for clinical transformation and application.