Electroactive nanoparticles loaded Silk protein/Chitosan macromolecular injectable hydrogel to improve therapeutic efficacy of mesenchymal stem cells in functional recovery after ischemic myocardial infarction

Abstract Background Currently, cardiac regeneration by stem cell-based tissue engineering is considered an important strategy for overcoming myocardial infarction. Therefore, this study is designed to explore the potential for differentiation of gold nanoparticles loaded injectable Silk protein/Chitosan hydrogel along with mesenchymal stem cells towards a cardiomyogenic phenotype. Methods The incorporated gold nanoparticles into chitosan-silk fibroin hydrogel (Au@Ch-SF) was validated by various analysis including FT-IR, NMR, XRD and SEM analysis. The major properties of Au@Ch-SF hydrogel such as weight loss, mechanical test and drug releasing activities also investigated. Further, the mesenchymal stem cells (MS) were encapsulated into hydrogel by incubating the MS cells with 100 µg/mL of Au@Ch-SF hydrogel in a humidified incubator at 37°C for 3 days in the presence of 5% CO2. In vitro toxicity effect of MS loaded Au@Ch-SF hydrogel was tested against cardiac myoblast H9C2 cells. Further, the tissue regenerative activities in myocardial infraction rats were examined by histology, apoptosis, and Cx43 cardiac-specific marker analysis. Results The gel formation time of Au@Ch-SF was comparatively lower than Ch and Ch-SF hydrogels which demonstrates the stronger intermolecular interactions between Ch and SF. The toxicity study showed that the prepared MS loaded Au@Ch-SF hydrogels did not possess toxicity against cardiac myoblast H9C2 cells. Further, the myocardial infarction rats were treated with MS loaded Au@Ch-SF hydrogel promotes the cardiac muscle fibers regeneration performance which was confirmed by β-MHC and Cx43 cardiac markers. Conclusions We demonstrate for the first time that encapsulation of MS with Au@Ch-SF hydrogels could promotes tissue regenerative activity in myocardial infraction tissues. The findings of this study suggest that MS encapsulated Au@Ch-SF hydrogels might be useful in the treatment of myocardial infarction.