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Updated: Oct 12, 2025
A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.
Published on: June 14, 2015
Restoring Cardiac Functions after Myocardial Infarction-Ischemia/Reperfusion via an Exosome Anchoring Conductive
Yang Zou1,2,3, Lan Li4,5, Yuan Li2
1College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Insights
Injectable conductive hydrogels carrying stem cell-derived exosomes effectively treat myocardial infarction-ischemia/reperfusion injury by prolonging exosome retention and improving cardiac function and tissue repair.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cardiovascular Research
Background:
- Myocardial infarction (MI) and subsequent reperfusion cause significant cardiac tissue damage, including dysfunction and fibrosis.
- Stem cell-derived exosomes show therapeutic potential for tissue repair but suffer from short half-lives and rapid clearance.
- Effective delivery systems are needed to enhance exosome retention and therapeutic efficacy in injured myocardial tissue.
Purpose of the Study:
- To develop an injectable, conductive hydrogel system for sustained delivery of exosomes to treat myocardial infarction-ischemia/reperfusion (MI-I/R) injury.
- To evaluate the therapeutic effects of the exosome-loaded hydrogel on cardiac function and myocardial tissue repair in a rat model.
Main Methods:
- Synthesized a conductive hydrogel using hyperbranched epoxy macromer grafted by aniline tetramer to cross-link thiolated hyaluronic acid and exosomes via an epoxy/thiol click reaction.
- Characterized the hydrogel composite system (Gel@Exo) for properties including gelation kinetics, injectability, conductivity, and cytocompatibility.
- Injected Gel@Exo into the injured hearts of rats and assessed cardiac function, fibrosis, and expression of key cardiac-related genes and proteins.
Main Results:
- The Gel@Exo system demonstrated controllable gelation, shear-thinning injectability, native myocardium-like conductivity, and stability.
- In vivo studies showed prolonged exosome retention in the ischemic myocardium and significant improvement in cardiac function (ejection fraction, fractional shortening).
- Gel@Exo treatment markedly reduced cardiac fibrosis and upregulated crucial cardiac-related proteins (Cx43, Ki67, CD31, α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-β1, MMP-9, Serca2a).
Conclusions:
- The conductive Gel@Exo hydrogel effectively prolongs exosome retention, enhances cell-to-cell interactions, and promotes angiogenesis and cell proliferation.
- This injectable composite system provides a promising therapeutic strategy for repairing injured myocardial tissues following MI-I/R.
- The developed hydrogel platform offers a novel approach to overcome the limitations of exosome-based therapies for cardiovascular diseases.
Abstract:
Both myocardial infarction (MI) and the follow-up reperfusion will lead to an inevitable injury to myocardial tissues, such as cardiac dysfunctions, fibrosis, and reduction of intercellular cell-to-cell interactions. Recently, exosomes (Exo) derived from stem cells have demonstrated a robust capability to promote angiogenesis and tissue repair. However, the short half-life of Exo and rapid clearance lead to insufficient therapeutic doses in the lesion area. Herein, an injectable conductive hydrogel is constructed to bind Exo derived from human umbilical cord mesenchymal stem cells to treat myocardial injuries after myocardial infarction-ischemia/reperfusion (MI-I/R). To this end, a hyperbranched epoxy macromer (EHBPE) grafted by an aniline tetramer (AT) was synthesized to cross-link thiolated hyaluronic acid (HA-SH) and thiolated Exo anchoring a CP05 peptide via an epoxy/thiol "click" reaction. The resulting Gel@Exo composite system possesses multiple features, such as controllable gelation kinetics, shear-thinning injectability, conductivity matching the native myocardium, soft and dynamic stability adapting to heartbeats, and excellent cytocompatibility. After being injected into injured hearts of rats, the hydrogel effectively prolongs the retention of Exo in the ischemic myocardium. The cardiac functions have been considerably improved by Gel@Exo administration, as indicated by the enhancing ejection fraction and fractional shortening, and reducing fibrosis area. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) results demonstrate that the expression of cardiac-related proteins (Cx43, Ki67, CD31, and α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-β1, MMP-9, and Serca2a) are remarkably upregulated. The conductive Gel@Exo system can significantly improve cell-to-cell interactions, promote cell proliferation and angiogenesis, and result in a prominent therapeutic effect on MI-I/R, providing a promising therapeutic method for injured myocardial tissues.
