Evaluation of an Injectable Hydrogel Based on Hyaluronic Acid–Chitosan/β‐Glycerophosphate‐Loaded Mesenchymal Stem Cells in Enhancing the Therapeutic Efficacy of Myocardial Infarction

Myocardial infarction (MI), which is due to cardiac dysfunction, results in morbidity and mortality. Moreover, the cellular activity of transplanted mesenchymal stem cells (MSCs) generally limits their therapeutic efficacy in the treatment of MI. Here, inject able hyaluronic acid-chitosan/β-glycerophosphate (HA-CS/β-GP) hydrogel-loaded MSCs are prepared, after which their effects on the treatment of MI are investigated. The synthesized HA-CS/β-GP hydrogels exhibit swelling ratio, an in vitro degradation value, and a gelatin time of 82.19 ± 4.1, 88.18% ± 2.4%, and 9 s, respectively. Further, rheological studies revealed that the elastic modulus of the HA-CS/β-GP hydrogels is ≥230 Pa, exhibiting large elastic to viscous modulus ratio, which indicates their mechanical strength. Furthermore, the in vitro 3T3 cell and MSC culture studies confirm the good biocompatibility of the HA-CS and HA-CS/β-GP hydrogels. The implantation of the synthesized hydrogels in the mouse MI model considerably improves the therapeutic effect of the MSCs (enhanced cardiac function, reduced cardiomyocyte apoptosis, and increased vascularization) for the first time. The innovative synergistic strategy of combining injectable HA-CS and HA-CS/β-GP hydro gels with MSCs may be suitable for the effective treatment of cardiac morbidity due to MIs.