Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 16, Pages 14619-14629Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b01886
Keywords
myocardial infarction; injectable hydrogel; adipose-derived stem cells; conductivity; hydrogen sulfide
Funding
- Excellent Young Scientists Fund by National Natural Science Foundation of China [31822020]
- National Natural Science Foundation of China [51473117, 31771030, 31870965]
- National Key Research and Development Program [2016YFC1101301, 2018YFC1105604]
- Tianjin Outstanding Youth Science Foundation [17JCJQJC46200]
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Hydrogen sulfide (H2S) exhibits extensive protective actions in cardiovascular systems, such as anti-inflammatory and stimulating angiogenesis, but its 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 (a small-molecule H2S donor) on partially oxidized alginate (ALG-CHO) to mimic the slow and continuous release of endogenous H2S. In addition, tetraaniline (a conductive oligomer) and adipose-derived stem cells (ADSCs) were introduced to form a stem cell-loaded conductive H2S-releasing hydrogel through the Schiff base reaction between ALG-CHO and gelatin. The hydrogel exhibited adhesive property to ensure a stable anchoring to the wet and beating hearts. After myocardial injection, longer ADSCs retention period and elevated sulfide concentration in rat myocardium were demonstrated, accompanied by upregulation of cardiac-related mRNA (Cx43, alpha-SMA, and cTnT) and angiogenic factors (VEGFA and Ang-1) and downregulation of inflammatory factors (tumor necrosis factor-alpha). Echocardiography and histological analysis strongly demonstrated an increase in the ejection fraction value and smaller infarction size, suggesting a remarkable improvement of the cardiac functions of Sprague-Dawley rats. The ADSC-loaded conductive hydrogen sulfide-releasing hydrogel dramatically promoted the therapeutic effects, offering a promising therapeutic strategy for treating myocardial infarction.
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