Effects of hydrogels loaded with hepatocyte growth factor on myocardial infarction

doi:10.12307/2023.547

Abstract

Abstract: BACKGROUND: Hepatocyte growth factor (HGF) has been shown to reduce cardiomyocyte apoptosis and improve cardiac function after myocardial infarction in diabetic rats. Intravenous injection or gene transfection is common methods of drug delivery in many previous studies; however, a sustained release system was used in very few studies.
OBJECTIVE: To investigate the effects of intramyocardial injection of hydrogels loaded with HGF on myocardial infarction.
METHODS: The sodium glycerophosphate/chitosan/sodium alginate/HGF composite hydrogel was prepared, and the compatibility of the hydrogel with cardiomyocytes and the release characteristics of growth factors in vitro were detected. A total of 54 male Sprage-Dawley rats (3 months old) were used for the establishment of myocardial infarction models by ligating the left anterior descending branch of the coronary artery and equally and randomly divided into three groups: untreated (multi-point injection of PBS at the edge of myocardial infarction), hydrogel without HGF (multi-point injection of sodium glycerophosphate/chitosan/sodium alginate composite hydrogel at the edge of myocardial infarction), and hydrogel with HGF (multi-point injection of sodium glycerophosphate/chitosan/sodium alginate/HGF composite hydrogel at the edge of myocardial infarction) groups.
RESULTS AND CONCLUSION: (1) Live-dead cell staining and CCK-8 assay showed that sodium glycerophosphate/chitosan/sodium alginate/hepatocyte growth factor hydrogel had good cytocompatibility and promoted the proliferation and survival of cardiomyocytes and could sustainably release HGF for more than 42 days. (2) The left ventricular volume and left ventricular volume at the end of diastole were significantly decreased in the hydrogel with HGF groups (P < 0.05), while the left ventricular ejection fraction and left ventricular short-axis shortening rate were significantly increased (P < 0.05) compared with the other two groups at 7, 14, 35 days after surgery. (3) Hemotoxylin-eosin and Masson stainings showed that the myocardial histopathology of rats in both treatment groups was significantly improved compared with the untreated group, and the most obvious improvement was found in the hydrogel with HGF group at 35 days after surgery. (4) TUNEL staining and α-smooth muscle actin immunofluorescence staining showed that the number of cardiomyocyte apoptosis was significantly decreased, while microvessel density was significantly increased in the hydrogel with HGF group compared with the other groups (P < 0.05). (5) These findings exhibit that intramyocardial injection of sodium glycerophosphate/chitosan/sodium alginate/hepatocyte growth factor composite hydrogel can inhibit cardiomyocyte apoptosis and myocardial fibrosis, promote revascularization, and delay left ventricular remodeling, improving cardiac function.

Key words: myocardial infarction, hydrogel, hepatocyte growth factor, cardiac function, cardiovascular disease, sustained drug release

CLC Number:

Wang Nanfeng, Shen Shengmei, Zhang Peisheng, Teng Wei. Effects of hydrogels loaded with hepatocyte growth factor on myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(30): 4802-4808.

Figures/Tables 12

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