Abstract 4743: Angiogenic Cytokine-conjugated Injectable Hydrogel Stabilized a Cardiac Infarct, Increased Blood Vessel Density and Improved Function
Introduction: We synthesized a novel, temperature-sensitive, aliphatic polyester hydrogel: [Poly (δ-valerolactone)-block-poly (ethylene glycol)-block-poly (δ-valerolactone) (PEG-PVL)]. This polymer dissolves in water at room temperature, but gels at 37 °C. We conjugated vascular endothelial growth factor (VEGF) to the gel to provide sustained release of the cytokine. We assessed the hypothesis that injecting the biodegradable hydrogel into the infarct region would provide a temporary scaffold to attenuate adverse cardiac remodeling, augment angiogenesis and prevent heart failure.
Methods: Myocardial infarction was generated in rats by left coronary artery ligation. PBS (100 μL), the new hydrogel (HG) or HG conjugated with VEGF (HG-VEGF) (n=8/group) were injected around the infarct region 1 week later. Cardiac function was evaluated by echocardiography (Echo) at multiple time points, and by pressure-volume measurements at 5 weeks. Blood vessel density was quantified immunohistochemically.
Results: HG-VEGF provided a sustained release of VEGF. Cardiac function: Ejection fraction (EF, by Echo) was significantly better in the HG than in the PBS group, and best in HG-VEGF (EF at 5 weeks =56±3%, 45±5% and 61±2%, respectively, p<0.05). Ventricular volumes, preload recruitable stroke work and end-systolic elastance were also better preserved (p<0.05) in the HG compared to the PBS group, and best in HG-VEGF. Morphometric studies: At 5 weeks, the infarct scar thinned and dilated in the PBS group, while scar thickness was preserved in HG and HG-VEGF groups (p<0.05). Scar length was smallest (p<0.05) and scar thickness greatest (p<0.05) in HG-VEGF. Blood vessel density: Factor VIII staining demonstrated fewest blood vessels in the scar and border zone of the PBS group, more in HG, and most in HG-VEGF (p<0.01).
Conclusions: Our novel, temperature-sensitive and biodegradable hydrogel attenuated adverse cardiac remodeling and improved ventricular function. The conjugation of VEGF to the hydrogel augmented these beneficial effects by increasing angiogenesis after a myocardial infarction. This cytokine-conjugated, biomimetic polymer could be used to prevent heart failure if injected around the infarct region during coronary revascularization.