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Updated: Nov 25, 2025
A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.
Published on: June 14, 2015
Myocardial protection by heparin-based coacervate of FGF10
Zhouguang Wang1,2,3, Yan Huang1,2, Yan He4
1School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, 325035, China.
Insights
An injectable fibroblast growth factor 10 (FGF10) coacervate effectively treated heart damage in mice after myocardial infarction (MI). This FGF10 coacervate improved cardiac function and reduced inflammation, unlike free FGF10.
Area of Science:
- Cardiovascular Research
- Biomaterials Science
- Regenerative Medicine
Background:
- Heart disease remains a leading global cause of mortality, with increasing incidence.
- Fibroblast growth factor 10 (FGF10) shows promise for treating heart disease but suffers from short half-life and low bioactivity.
- Developing effective delivery systems for FGF10 is crucial for its therapeutic application.
Purpose of the Study:
- To design an injectable coacervate formulation for FGF10 delivery.
- To evaluate the efficacy of FGF10 coacervate in a mouse model of acute myocardial infarction (MI).
- To compare the therapeutic effects of FGF10 coacervate with free FGF10 and saline treatment.
Main Methods:
- An injectable FGF10 coacervate was synthesized and characterized.
- Mice underwent induced acute myocardial infarction (MI) and were treated with FGF10 coacervate, free FGF10, or saline.
- Cardiac function was assessed using echocardiography, and myocardial tissue was analyzed histologically and via gene/protein expression analysis.
- Downstream signaling pathways (FGFR, PI3K/Akt, ERK1/2) were investigated using Western blotting.
Main Results:
- FGF10 coacervate significantly preserved cardiac contractility and reduced ventricular dilation post-MI compared to free FGF10 and saline.
- Histological analysis revealed reduced myocardial inflammation and fibrosis in FGF10 coacervate-treated mice.
- FGF10 coacervate enhanced angiogenesis by promoting endothelial and mural cell proliferation and stabilized vasculature.
- Gene expression analysis showed increased cardiac-associated and angiogenic factors, and decreased inflammatory markers.
- Western blot results indicated that FGF10 coacervate effectively activated key downstream signaling pathways (p-FGFR, PI3K/Akt, ERK1/2).
Conclusions:
- A single injection of FGF10 coacervate provides sustained therapeutic benefits for acute myocardial infarction (MI) in mice.
- The coacervate formulation enhances FGF10 bioactivity and stability, leading to improved cardiac function and reduced injury.
- FGF10 coacervate represents a promising strategy for managing heart disease by promoting cardiac repair and regeneration.
Abstract:
Heart disease is still the leading killer all around the world, and its incidence is expected to increase over the next decade. Previous reports have already shown the role of fibroblast growth factor10 (FGF10) in alleviating heart diseases. However, FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity. Here, an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction (MI) model. As shown in our echocardiographic results, a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI. It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment. Furthermore, FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells. However, with the same dosage, no statistically significant difference was shown between free FGF10, heparin+FGF10 and saline treatment, especially in long term. On another hand, FGF10 coacervate also increased the expression of cardiac-associated the mRNA (cTnT, Cx43 and α-SMA), angiogenic factors (Ang-1 and VEGFA) and decreased the level of inflammatory factor (tumor necrosis factor-α). The downstream signaling of the FGF10 was also investigated, with the western blot results showing that FGF10 coacervate activated the p-FGFR, PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10. In general, it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.
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