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Updated: Jul 12, 2025
Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after
Priya Mohindra1,2, Justin X Zhong1,2, Qizhi Fang3
1UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.
Insights
Decorin-loaded microrods significantly improved heart function and reduced fibrosis after myocardial infarction. This biomaterial approach offers a promising strategy for treating heart failure and promoting cardiac tissue regeneration.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Regenerative Medicine
Background:
- Heart failure (HF) is a major global health issue, often stemming from myocardial infarction (MI).
- Cardiac fibrosis post-MI impairs heart function and limits tissue regeneration.
- Current treatments for MI-induced cardiac remodeling are limited.
Purpose of the Study:
- To develop and evaluate decorin-loaded hyaluronic acid microrods for attenuating cardiac fibrosis and improving cardiac function after acute myocardial injury.
- To assess the therapeutic efficacy of decorin microrods in a rat model of ischemia-reperfusion myocardial infarction.
Main Methods:
- Hyaluronic acid (HA) microrods were fabricated and loaded with the anti-fibrotic proteoglycan decorin, demonstrating controlled release kinetics.
- Intramyocardial injections of saline, microrods, decorin microrods, or free decorin were administered to male rats post-MI.
- Cardiac function was assessed via echocardiography, and cardiac remodeling was evaluated using histology and immunofluorescence staining.
Main Results:
- Decorin microrod treatment significantly increased the change in ejection fraction (EF) compared to saline and free decorin groups at 8 weeks post-MI.
- A trend towards reduced end-diastolic volume was observed in the decorin microrod group, indicating favorable ventricular remodeling.
- Quantitative analysis revealed significant reductions in cardiac fibrosis and cardiomyocyte hypertrophy in rats treated with decorin microrods compared to saline controls.
Conclusions:
- Decorin-loaded HA microrods effectively attenuate cardiac fibrosis and hypertrophy post-myocardial infarction.
- This biomaterial strategy demonstrates significant therapeutic potential for improving cardiac function and remodeling after acute myocardial injury.
- The findings provide a foundation for rationally designed biomaterials to treat cardiovascular diseases.
Abstract:
Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.
