Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis

Abstract Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladd...

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Main Authors: Yulong Fu, Canran Gao, Hailing Zhang, Jing Liu, Boxuan Li, Wei Chen, Xiuping Chen, Xue Lin, Ligang Fang, Zhihong Wang
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202500036
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author Yulong Fu
Canran Gao
Hailing Zhang
Jing Liu
Boxuan Li
Wei Chen
Xiuping Chen
Xue Lin
Ligang Fang
Zhihong Wang
author_facet Yulong Fu
Canran Gao
Hailing Zhang
Jing Liu
Boxuan Li
Wei Chen
Xiuping Chen
Xue Lin
Ligang Fang
Zhihong Wang
author_sort Yulong Fu
collection DOAJ
description Abstract Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB‐ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G′) increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB‐ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB‐ECM treatment. Overall, this new injectable hydrogel based on FSB‐ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure.
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spelling doaj-art-64f61606a681477cbf975ec46df1f5432025-08-20T02:10:19ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.202500036Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and AngiogenesisYulong Fu0Canran Gao1Hailing Zhang2Jing Liu3Boxuan Li4Wei Chen5Xiuping Chen6Xue Lin7Ligang Fang8Zhihong Wang9Institute of Transplant Medicine School of Medicine Nankai University Tianjin 300071 ChinaPeking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS&PUMC) Beijing 100005 ChinaInstitute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300192 ChinaInstitute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300192 ChinaInstitute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300192 ChinaPeking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS&PUMC) Beijing 100005 ChinaState Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macao 999078 ChinaPeking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS&PUMC) Beijing 100005 ChinaPeking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS&PUMC) Beijing 100005 ChinaInstitute of Transplant Medicine School of Medicine Nankai University Tianjin 300071 ChinaAbstract Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB‐ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G′) increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB‐ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB‐ECM treatment. Overall, this new injectable hydrogel based on FSB‐ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure.https://doi.org/10.1002/advs.202500036extracellular matrixfish swim bladderheart failureinjectable hydrogel
spellingShingle Yulong Fu
Canran Gao
Hailing Zhang
Jing Liu
Boxuan Li
Wei Chen
Xiuping Chen
Xue Lin
Ligang Fang
Zhihong Wang
Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
Advanced Science
extracellular matrix
fish swim bladder
heart failure
injectable hydrogel
title Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
title_full Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
title_fullStr Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
title_full_unstemmed Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
title_short Fish Swim Bladder‐Derived ECM Hydrogels Effectively Treat Myocardial Ischemic Injury through Immunomodulation and Angiogenesis
title_sort fish swim bladder derived ecm hydrogels effectively treat myocardial ischemic injury through immunomodulation and angiogenesis
topic extracellular matrix
fish swim bladder
heart failure
injectable hydrogel
url https://doi.org/10.1002/advs.202500036
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