Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling.

AIMS: Myocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling. METHODS AND RESULTS: MI was induced in rabbits by coronary artery ligation; 4 days later, 200 microL Dex-PCL-HEMA/PNIPAAm gel solution was injected into the infarcted myocardium. Injection of phosphate-buffered saline served as control. Thirty days after treatment, histological analysis indicated that injection of the biomaterial prevented scar expansion and wall thinning compared with controls. Echocardiography studies showed that injection of hydrogel increased left ventricular ejection fraction and attenuated left ventricular systolic and diastolic dilatation. Haemodynamic analysis demonstrated improved cardiac function following implantation of the hydrogel. CONCLUSION: These results suggest that injection of thermosensitive Dex-PCL-HEMA/PNIPAAm hydrogel is an effective strategy that prevents adverse cardiac remodelling and dysfunction in MI rabbits.

[Effect of a novel injectable hydrogel implant on ventricular remodeling in rabbits with experimental myocardial infarction].

OBJECTIVE: To observe whether injectable hydrogel implantation could prevent adverse cardiac remodeling and preserve cardiac function in rabbits with myocardial infarction (MI). METHODS: A novel injectable hydrogel, the copolymer MPM/alpha-CD, which self-assembled between alpha-cyclodextrin and methoxy polyethylene glycol-poly (caprolactone)-(dodecanedioic acid)-poly (caprolactone)-methoxypolyethylene glycol triblock polymer, was synthesized by chemical crosslinking and characterized by biocompatibility and biodegradability. Experimental MI was induced in male rabbits by coronary artery ligation. The MI rabbits were randomly divided into hydrogel group (200 microl MPM/alpha-CD were injected into the infarcted myocardium 7 days after MI) and control group (equal volume phosphate buffered saline myocardial injection, n = 8 each). Four weeks after MPM/alpha-CD implantation, echocardiography, histochemistry and immunohistochemistry were performed. RESULTS: Left ventricle ejection fraction was significantly improved in the hydrogel-treated group (56.1% +/- 8.4%) than that in the control group (37.3% +/- 6.4%, P < 0.05). Histological analysis indicated that hydrogel degraded 4 weeks after hydrogel injection, and prevented scar expansion and wall thinning [(3.08 +/- 0.32) mm vs. (2.18 +/- 0.46) mm in control group, P < 0.05]. Neovasculature formation was similar between the hydrogel group [(100.8 +/- 2.4)/mm(2)] and the control [(98.5 +/- 2.9)/mm(2), P > 0.05]. CONCLUSION: MPM/alpha-CD could serve as an excellent injectable biomaterial for improves cardiac function and attenuating scar expansion and left ventricular dilation in MI rabbits.

Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction.

Myocardial infarction (MI) and the subsequent heart failure remain one of the leading causes of morbidity and mortality world wide. A number of studies have demonstrated that bioderived materials improve cardiac function after implantation because of their angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricular (LV) function through its prevention of paradoxical systolic bulging. To test this hypothesis, infarction was induced in rabbit myocardium by coronary artery ligation. After 1 week, 200-microL alpha-cyclodextrin (alpha-CD)/MPEG-PCL-MPEG hydrogel was injected into the infarcted myocardium. Injection of phosphate buffered saline (PBS) served as controls. Twenty-eight days after the treatment, histological analysis indicated that the injection of hydrogel prevented scar expansion and wall thinning compared with the control (p < 0.05) without more microvessel density in infarcted myocardium (p = 0.70). LV ejection fraction, determined by echocardiography, was significantly greater in the hydrogel-treated group (56.09% +/- 8.42%) than the control group (37.26% +/- 6.36%, p = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 +/- 0.33 cm and 1.74 +/- 0.30 cm, respectively, in the control group. Smaller LV end-diastolic diameter (1.61 +/- 0.26 cm, p = 0.005) and smaller end-systolic diameter (1.17 +/- 0.23 cm, p = 0.001) were found in the hydrogel-treated group. These results suggest that alpha-CD/MPEG-PCL-MPEG hydrogel could serve as an injectable biomaterial that prevents LV remodeling and dilation for the treatment of MI.