Biodegradable Synthetic Graft with Sustained Hydrogen Sulfide Release Promotes Endothelial Cell Growth

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter that possesses multiple pathological and physiological functions, including anti-inflammation, anti-thrombosis, anti-calcification, inhibition of intimal hyperplasia, and promotion of angiogenesis. Therefore, we aim to design an H₂S-releasing resorbable synthetic graft that utilizes the therapeutic benefits of the H₂S to modulate the graft regeneration. To ease fabrication of the H₂S-releasing graft, we have designed a pair of functional polyesters that are electrospinnable and photocurable to form an elastic fibrous conduit. The conduit bears free thiol groups that are conjugated with a methacrylated H₂S donor through thiol-ene click chemistry to form an H₂S-releasing graft. The graft can sustainably release H₂S over ∼12 days in vitro. Differing from prior designs, the H₂S-releasing graft simultaneously possesses key features of a robust elasticity, and suitable mechanical properties, degradation rate and porosity. At the proof-of-concept stage, we examined the H₂S stimulation on endothelial cell growth using the graft with a low H₂S releasing rate. The results demonstrated that the graft with sustained H₂S release could significantly promote endothelial cell growth in vitro. This work paved the way for in vivo evaluation of the H₂S-releasing graft.