In situ self-assembled stimulus-responsive and conductive hydrogel modulate myocardial infarction inflammatory homeostasis via PPARα/NFκB signaling and enhance the therapeutic efficacy of hiPSC-CMs
Stem cell therapies are emerging as promising strategies for repair after myocardial infarction (MI), but the repair efficacy is limited by the poor cardiac microenvironment represented by the inflammatory response, as well as oxidative stress, and adverse electrical coupling. Here, we developed an injectable supramolecular hydrogel (HCPA) that modulates the infarct microenvironment and accelerates myocardial repair by encapsulating human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). HCPA hydrogel not only exhibited excellent reactive oxygen species (ROS) response in order to minimize oxidative stress but also possessed desirable electrical conductivity for the reintegration of electrical impulses. Critically, RNA sequencing demonstrated that the PPARα/NFκB pathway contributed significantly to the HCPA hydrogel-promoted macrophage polarization from M1-type to M2-type, thus alleviating inflammatory responses. HCPA hydrogel harboring hiPSC-CMs increased retention of hiPSC-CMs and improved cardiac function in MI mice. This study represents a new integrated therapeutic option for MI and provides insights for the development of novel biomaterials in the field of tissue engineering.
Authors
- Haodong Li (ORCID: https://orcid.org/0000-0003-0532-9481)
- Chaoqian Xu
- Ting Zhang (ORCID: https://orcid.org/0000-0002-6426-5812)
- Songyan Jiao
- Lina Xuan (ORCID: https://orcid.org/0000-0003-2127-592X)
- Qi Yu
- Mingyu Zhang (ORCID: https://orcid.org/0000-0002-2065-4365)
- Jie Liu (ORCID: https://orcid.org/0000-0001-6209-6886)
- Mingyu Yang (ORCID: https://orcid.org/0000-0003-0986-3825)
- S Fan
- Hao Wang (ORCID: https://orcid.org/0009-0001-6738-4577)
- ZHANG Yong
- Deqiang Chen
- Mei Dong
- Xiaoping Leng
- Siyu Wang (ORCID: https://orcid.org/0009-0000-6949-9514)
- Xiyang Zhang
- Jianjun Guo
- Dongping Liu
- Haodi Wu
- Baofeng Yang
- Junting Ren
- Manyu Gong
- Ying Zhang
- Lihua Sun
- Yanwei Zhang
Institutions
- Harbin Medical University (CN)
- University of Pittsburgh (US)
- Third Affiliated Hospital of Harbin Medical University (CN)
- Heilongjiang International University (CN)
- Second Affiliated Hospital of Harbin Medical University (CN)
- Chongqing Three Gorges University (CN)
Publication Details
- Journal
- Bioactive Materials
- Published
- 2026-04-20
- DOI
- https://doi.org/10.1016/j.bioactmat.2026.03.050
- Primary Topic
- NF-κB Signaling Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Heilongjiang Province
- Heilongjiang Provincial Postdoctoral Science Foundation
- National Major Science and Technology Projects of China
- Chinese Academy of Medical Sciences Initiative for Innovative Medicine
- Science Fund for Distinguished Young Scholars of Heilongjiang Province