(335e) Development of Injectable Citric Acid-Based Polyester Hydrogel with Sustained Mydgf Delivery Capability for Improved Post-MI Heart Healing

Cardiac dysfunction, specifically myocardial infarction (MI) ranks among the major causes of morbidity and mortality in current times. Intramyocardial therapeutics injection is an efficient method of enhancing cardiac performance after experiencing ischemic MI. Myeloid-derived growth factor (Mydgf) is a newly found protein secreted by bone marrow-derived monocytes and macrophages. It is responsible for cardiac myocyte survival, angiogenesis, and shows promise in promoting cardiac recovery after MI. However, in order to maintain the protein level, several days of continuous perfusion is needed, which severely limits the clinical translation of this protein. Here, we introduce an injectable citric acid-based polyester hydrogel which is capable of loading Mydgf with an extended release capability in vivo and demonstrate an innovative new potential treatment of MI. Polyester hydrogel with tunable mechanical properties have been successfully synthesized from biocompatible monomers including citric acid, PEG-diol and thiol containing moieties. We demonstrated the suitability of using polyester hydrogel for the local, controlled, intramyocardial delivery of Mydgf. Importantly, injection of the Mydgf-hydrogel into the LV of rats with a MI showed significant improvements in cardiac morphology and functionality at 4 weeks relative to the controls. We further reveal the functional roles of Mydgf-hydrogel in promoting angiogenesis and reducing cardiac cell apoptosis.