In situ depot comprising phase-change materials that can sustainably release a gasotransmitter HS to treat diabetic wounds.

Patients with diabetes mellitus are prone to develop refractory wounds. They exhibit reduced synthesis and levels of circulating hydrogen sulfide (HS), which is an ephemeral gaseous molecule. Physiologically, HS is an endogenous gasotransmitter with multiple biological functions. An emulsion method is utilized to prepare a microparticle system that comprises phase-change materials with a nearly constant temperature of phase transitions to encapsulate sodium hydrosulfide (NaHS), a highly water-labile HS donor. An emulsion technique that can minimize the loss of water-labile active compounds during emulsification must be developed. The as-prepared microparticles (NaHS@MPs) provide an in situ depot for the sustained release of exogenous HS under physiological conditions. The sustained release of HS promotes several cell behaviors, including epidermal/endothelial cell proliferation and migration, as well as angiogenesis, by extending the activation of cellular ERK1/2 and p38, accelerating the healing of full-thickness wounds in diabetic mice. These experimental results reveal the strong potential of NaHS@MPs for the sustained release of HS for the treatment of diabetic wounds.