Synergistic effects of biomaterials and extracellular vesicles in treating myocardial infarction: A systematic review of preclinical studies

Extracellular vesicles (EVs) combined with biomaterials have shown promise in treating myocardial infarction (MI), with potential to alleviate inflammation, oxidative stress, and apoptosis while improving cardiac function. However, systematic evaluation is needed. This meta-analysis utilized data from PubMed, Web of Science, Scopus, EMBASE, and Ovid medicine from their inception to May 2025. Relevant outcomes were analyzed using GetData Graph Digitizer 2.26 and Review Manager 5.4 software. The quality of studies was assessed using the SYRCLE risk of bias tool and CAMARADES checklist. We measured 12 indicators across cardiac function, fibrosis, apoptosis, and inflammation. The meta-analysis included 33 studies. Compared to EV monotherapy, the combination of EVs with biomaterials significantly improved several cardiac functions and structural parameters. These include: Ejection Fraction (SMD = 1.79; p < 0.00001); Fractional Shortening (SMD = 1.61; p < 0.00001); Myocardial Fibrosis (SMD = -1.83; p = 0.002); Additionally, IL-6 (SMD = -2.55; p = 0.01) and TNF-α (SMD = -1.18; p = 0.01), as well as apoptosis levels (SMD = -3.72; p < 0.0001), were markedly reduced. Among them, intramyocardial injection of MSC-derived EVs combined with hydrogel is the most widely used combination therapy. EVs combined with biomaterials enhance cardiac recovery in MI models with no significant safety issues, highlighting their potential therapeutic benefits. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) is one of the leading causes of death and disease burden. Over the past 20 years, extracellular vesicles (EVs) have undergone a remarkable journey and are now poised on the brink of becoming the next generation of cell-free therapeutic tools. Our study aims to quantitatively analyze the efficacy and safety of combining biomaterials with EVs compared to EVs alone in MI through a meta-analytical mapping approach. This is the comprehensive meta-analysis summarizing the effectiveness and safety of various biomaterials combined with EV therapy, highlighting the role of biomaterials in advancing the field. It provides valuable insights for researchers exploring the clinical translation of EV-based therapies.