Novel fabrication of bioengineered injectable chitosan hydrogel loaded with conductive nanoparticles to improve therapeutic potential of mesenchymal stem cells in functional recovery after ischemic myocardial infarction

Abstract

In recent decades, myocardial regeneration through stem cell transplantation and tissue engineering has been viewed as a promising technique for treating myocardial infarction. As a result, the researcher attempts to see whether co-culturing modified mesenchymal stem cells with Au@Ch-SF macro-hydrogel and H9C2 may help with tissue regeneration and cardiac function recovery. The gold nanoparticles (Au) incorporated into the chitosan-silk fibroin hydrogel (Au@Ch-SF) were validated using spectral and microscopic examinations. The most essential elements of hydrogel groups were investigated in detail, including weight loss, mechanical strength, and drug release rate. Initially, the cardioblast cells (H9C2 cells) was incubated with Au@Ch-SF macro-hydrogel, followed by mesenchymal stem cells (2 × 10⁵) were transplanted into the Au@Ch-SF macro-hydrogel+H9C2 culture at the ratio of 2:1. Further, cardiac phenotype development, cytokines expression and tissue regenerative performance of modified mesenchymal stem cells treatment were studied through various in vitro and in vivo analyses. The Au@Ch-SF macro-hydrogel gelation time was much faster than that of Ch and Ch-SF hydrogels, showing that Ch and SF exhibited greater intermolecular interactions. The obtained Au@Ch-SF macro-hydrogel has no toxicity on mesenchymal stem cells (MS) or cardiac myoblast (H9C2) cells, according to the biocompatibility investigation. MS cells co-cultured with Au@Ch-SF macro-hydrogel and H9C2 cells also stimulated cardiomyocyte fiber restoration, which has been confirmed in myocardial infarction rats using -MHC and Cx43 myocardial indicators. We developed a novel method of co-cultured therapy using MS cells, Au@Ch-SF macro-hydrogel, and H9C2 cells which could promote the regenerative activities in myocardial ischemia cells. These study findings show that co-cultured MS therapy might be effective for the treatment of myocardial injury.

Keywords: Chitosan hydrogel; Gold nanoparticles; Ischemic myocardial infarction; Stem cells.