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Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair

Author

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  • Dashuai Zhu

    (North Carolina State University
    University of North Carolina at Chapel Hill & North Carolina State University)

  • Zhenhua Li

    (North Carolina State University
    University of North Carolina at Chapel Hill & North Carolina State University)

  • Ke Huang

    (North Carolina State University
    University of North Carolina at Chapel Hill & North Carolina State University)

  • Thomas G. Caranasos

    (University of North Carolina at Chapel Hill)

  • Joseph S. Rossi

    (University of North Carolina at Chapel Hill)

  • Ke Cheng

    (North Carolina State University
    University of North Carolina at Chapel Hill & North Carolina State University)

Abstract

Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural “mold” for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.

Suggested Citation

  • Dashuai Zhu & Zhenhua Li & Ke Huang & Thomas G. Caranasos & Joseph S. Rossi & Ke Cheng, 2021. "Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21682-7
    DOI: 10.1038/s41467-021-21682-7
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    Cited by:

    1. Doyeon Koo & Xiao Cheng & Shreya Udani & Sevana Baghdasarian & Dashuai Zhu & Junlang Li & Brian Hall & Natalie Tsubamoto & Shiqi Hu & Jina Ko & Ke Cheng & Dino Di Carlo, 2024. "Optimizing cell therapy by sorting cells with high extracellular vesicle secretion," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. S. M. Shatil Shahriar & Alec D. McCarthy & Syed Muntazir Andrabi & Yajuan Su & Navatha Shree Polavoram & Johnson V. John & Mitchell P. Matis & Wuqiang Zhu & Jingwei Xie, 2024. "Mechanically resilient hybrid aerogels containing fibers of dual-scale sizes and knotty networks for tissue regeneration," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Zhang, Qianqian & Zhao, Lei & Ran, Fen, 2022. "Reducible, recyclable and reusable (3R) hydrogel electrolyte membrane based on Physical&Chemical Bi-networks and reversible sol-gel transition," Renewable Energy, Elsevier, vol. 194(C), pages 80-88.

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