Bio-functionalized hydrogel patches of chitosan for the functional recovery of infarcted myocardial tissue

The aim of this work was to assess the potential benefits of the enrichment of a chitosan hydrogel patch with secretome and its epicardial implantation in a murine model of chronic ischemia, focusing on the potential to restore the functional capacity of the heart. Thus, a hydrogel with a final polymer concentration of 3 % was prepared from chitosan with an acetylation degree of 24 % and then bio-functionalized with a secretome produced by mesenchymal stromal cells. The identification of proteins in the secretomes showed the presence of several proteins known to have beneficial effects on cardiac muscle repair. Then chitosan hydrogels were immersed in secretome. The protein incorporation in the hydrogel and their release over time were studied, demonstrating the ability of the gel to retain and then deliver proteins (around 40 % was released in the first 6 h, and then a plateau was reached). Moreover, mechanical analysis exhibited that the patches remained suturable after enrichment. Finally, bio-functionalized hydrogel patches were sutured onto the surface of the infarcted myocardium in rat. Thirty days after, the presence of enriched hydrogels induced a reversion of cardiac function which seems to come mainly from an improvement of left ventricle systolic performance and contractility. • Development of a chitosan patch with well-chosen physicochemical properties • Patch enrichment with a secretome produced by mesenchymal stromal cells • Identification in secretome of several proteins beneficial to cardiac regeneration • Feasible enrichment of the hydrogel patches with secretome • Beneficial effects of these acellular biofunctionalized patches on cardiac function