Gelatin Methacryloyl Bioadhesive Improves Survival and Reduces Scar Burden in a Mouse Model of Myocardial Infarction
Leon M. Ptaszek, Roberto Portillo‐Lara, Ehsan Shirzaei Sani, Chunyang Xiao, Jason D. Roh, Xuejing Yu, Pablo A. Ledesma, Chu Hsiang Yu, Nasim Annabi, Jeremy N. Ruskin
Abstract
Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction ( MI ). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (Gel MA ) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof‐of‐concept study was to evaluate the cardioprotective potential of Gel MA in a mouse model of MI . Methods and Results The physical properties of Gel MA bioadhesive hydrogel were optimized in vitro. Impact of Gel MA bioadhesive hydrogel on post‐ MI recovery was then assessed in vivo. In 20 mice, Gel MA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI . An additional 20 mice underwent MI but received no Gel MA bioadhesive hydrogel. Survival rates were compared for Gel MA ‐treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post‐ MI were 89% for Gel MA ‐treated mice and 50% for untreated mice ( P =0.011). Left ventricular contractile function was better in Gel MA ‐treated than untreated mice (fractional shortening 37% versus 26%, P <0.001). Average scar burden in Gel MA ‐treated mice was lower than in untreated mice (6% versus 22%, P =0.017). Conclusions Epicardial Gel MA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post‐ MI survival compared with control animals. In addition, Gel MA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.