Electrospun Polymer Fiber Mats for Persulfide Prodrug Delivery

Persulfides (RSSH) and hydrogen sulfide (H ₂S) are endogenously produced bioactive molecules that serve important roles in vasculogenesis and tissue repair processes. Through the physical incorporation of RSSH/H ₂S donors into electrospun fibers, we designed polymeric fiber mats that released provasculogenic and cytoprotective reactive sulfur species over biologically relevant time scales. The release of small molecules from the fiber mats showed that 20–50% of the analytes were released from the scaffolds after 4 h. Tube formation assays indicated that the persulfide donors improved tube formation in human microvascular endothelial cells (HMVECs) over baseline levels under oxidative conditions (H ₂O ₂). Analysis of HMVECs on the electrospun fiber mats demonstrated cell viability >80% for all groups tested. This design enables controlled release of small-molecule prodrugs as a novel method toward the formation of tissue engineering constructs that deliver reactive sulfur species, including RSSH, addressing an ongoing challenge in the field of tissue engineering.