Hydrogen Sulfide-Releasing Hydrogel Encapsulating ADSCs For Myocardial Infarction Treatment

Hydrogen sulfide（H₂S）exhibits extensive protective functions in cardiovascular systems,such as anti-inflammation and stimulating angiogenesis,but the therapeutic potential is severely discounted by the short half-life and the poorly controlled releasing behavior.Herein,we developed a macromolecular H₂S prodrug by grafting 2-aminopyridine-5-thiocarboxamide（APTC,a small molecule H₂S donor）on partially oxidized alginate（ALG-CHO）to mimic the slow and continuous release of endogenous H₂S.In addition,tetraaniline（TA,a conductive oligomer）and adipose-derived stem cells（ADSCs）were introduced to form stem cells-loaded conductive H₂S-releasing hydrogel through Schiff base reaction between ALG-CHO and gelatin.The hydrogel exhibits adhesive property（5.2 k Pa）to ensure a stable anchoring to beating hearts.After myocardial injection,longer ADSCs retention period and higher sulfide concentration in rat myocardium were demonstrated,accompanying by the upregulation of cardiac related m RNA such as connexin 43（Cx43）,α-smooth muscle actin（α-SMA）,cardiac troponin T（c Tn T）,angiogenic factors vascular endothelial growth factor A（VEGFA）and angiopoietin-1（Ang-1）,and down-regulation of inflammatory factors（tumor necrosis factor-α,TNF-α）.Echocardiography and histological analysis demonstrate a sharp increase in ejection fraction（EF）value（from 32.2%to 66.6%）and a significant reduction in infarction size（from 50.3%to 24.6%）,suggesting a remarkable improvement of the cardiac functions of SD rats.The ADSCs-loaded conductive hydrogen sulfide-releasing hydrogel dramatically restores the heart functions after acute myocardial infarction（MI）,offering a promising therapeutic strategy for treating MI.