Self-cross-linkable hydrogels composed of partially oxidized alginate and gelatin for myocardial infarction repair

Abstract

Calcium cross-linked alginate hydrogel has shown positive results for the treatment of myocardial infarction in both acute and chronic rat models. However, cross-linked alginate hydrogels possess poor mechanical properties, uncontrollable degradation, and poor cell adhesion and infiltration. In this study, covalent cross-linking of partially oxidized alginate and gelatin hydrogel was developed for myocardial infarction treatment, as compared to cross-linked alginate hydrogel and saline. Specifically, the gelation process, mechanical properties, and biodegradation of both cross-linked alginate hydrogel and oxidized alginate and gelatin hydrogel were examined in vitro and in vivo; and a rat myocardial infarction model was developed by injecting hydrogel into hearts, and postinjection, echocardiography was performed at 2, 4, and 6 weeks, respectively. Matrix metalloprotease-2/9 activity was also examined by in situ zymography on frozen slices of the treated hearts. Based on the results, that both hydrogels enhanced scar thickness and attenuated heart remodeling compared with the saline control group and that, compared to cross-linked alginate hydrogel, oxidized alginate and gelatin hydrogel exhibited the increased mechanical strength, enhanced angiogenesis, and stronger cell-recruiting capacity. It has also been illustrated that oxidized alginate and gelatin hydrogel–treated hearts have much weaker cardiac remodeling, enhanced extracellular matrix accumulation, and reduced matrix metalloprotease activity than cross-linked alginate hydrogel–treated ones. All results suggest oxidized alginate and gelatin hydrogel may be more suitable for the myocardial infarction treatment.