Introduction: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. Patient concerns: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. Diagnosis: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). Interventions: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. Outcomes: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. Conclusion: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation. Graphical

Introduction: This study evaluates the efficacy of a combined regimen based on injectable hydrogels for the treatment of experimental myocardial infarction. Patient concerns: Myocardial infarction is an acute illness associated with a decline in quality of life and increased mortality. Experimental myocardial infarction models can facilitate disease research for developing therapies that effectively manage disease progression and promote tissue repair. Diagnosis: An experimental myocardial infarction animal model was established using the ligation method of the anterior descending branch of the left coronary artery (LAD). Interventions: The efficacy of combining hydrogels with various therapies for intramyocardial injection was assessed to evaluate the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. Outcomes: The literature review spanned PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers were included in the meta-analysis according to the inclusion and exclusion criteria. When analyzing a murine small animal model, the combination therapy group using hydrogel showed a significant improvement in the primary outcome of left ventricular ejection fraction, with an overall effect size of 11.68 (95% confidence interval (CI): 10.24,13.12) compared to the group receiving hydrogel injection alone. The overall effect size for short-axis shortening was 6.25 (95% CI: 5.98,6.52). Subgroup analysis suggested that the source of hydrogel had a minor impact on the treatment outcome. Conclusion The present study demonstrated that combining hydrogel with other therapies effectively treated myocardial infarction, improving heart function and morphology. More research and clinical trials should be conducted using large animal models for further study and validation.