Abstract
Impaired angiogenesis and induced refractory lesions of the chronic wounds are common complications observed in diabetes mellitus. Hydrogen sulfide (H2S) has been reported as a therapeutic gas transmitter, with the regulatory roles of cell migration and proliferation as well as capillary morphogenesis for endothelial cells. Sulfide salts such as sodium hydrosulfide (NaHS) have been used as a H2S precursor to study the biological effects of this gas compound. However, when encountered water, NaHS dissociates and generates a large amount of H2S over a very short time period. To overcome this concern, a hydrophobic microsphere system that is composed of paraffin wax (PW) and 1-tetradecanol (TD) and encapsulated with NaHS was developed. It was found that the NaHS-encapsulated microsphere system could sustain release of H2S for 48 h. As compared to that treated with free form NaHS, sustained release of H2S from the as-prepared microsphere system showed a significant promotion of human umbilical vein endothelia cell (HUVEC) proliferation and human epidermis keratinocyte migration, suggesting that sustained H2S release promotes the appearance of an angiogenesis phenotype. In the in vivo study, the wound closure rate in db/db diabetic mice was significantly faster in the group that was treated with the microsphere system than that treated with free form NaHS and the untreated control group. These experimental results demonstrate that the prepared microsphere system exhibited the features of bioavailability and protect the function of NaHS from rapid dissociation, suggesting that the sustained release of H2S is beneficial to chronic diabetic wounds in reference to the frequently treatment of free form NaHS.