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A new glucose-responsive injectable hydrogel for mesenchymal stem cells transplantation to rat myocardial infarction heart

Research Project

Project/Area Number 21K20526
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0403:Biomedical engineering and related fields
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Le Hue Thi  国立研究開発法人国立循環器病研究センター, 研究所, リサーチフェロー (80906280)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsinjectable hydrogel / myocardial infarction / sorbitol response / adverse remodeling / MSCs / material distribution / material retention / cardiac function / viscosity / wide-distribution / long-retention / sorbitol responsive / mesenchymal stem cell / cell viability / ventricular regeneration
Outline of Research at the Start

This study aims to confirm a new concept of injectable hydrogel with elongates mesenchymal stem cells (MSCs) viability in the rat heart. This hydrogel enables sol-gel transition automatically via simple diffusion of glucose molecules to the host body without exogenous stimuli such as thermal, UV light, irradiation used for gelation of reported injectable hydrogels. Using an animal model of myocardial infarction, we next to investigate the effect of this MSCs-hydrogel complex on cardiac function, and ventricular regeneration.

Outline of Final Research Achievements

A new sugar-responsive injectable hydrogel was developed for the treatment of myocardial infarction by combining it with or without mesenchymal stem cells (MSCs). We achieved the proof-of-concept in which the material solution included poly (3-acrylamidophenylboronic acid-co-acrylamide) (BAAm), poly(vinyl alcohol) (PVA), and sorbitol can become an in-situ gel after injection into the tissue via simple diffusion of the sorbitol to surrounding tissue. It has been found that those materials have no cytotoxicity with several cell types involving MSCs, smooth muscle cells, and fibroblast cells. Using a myocardial infarction model, we demonstrated that intramyocardial injection of this material prevents adverse cardiac remodeling, resulting in preserved cardiac function. The current data was published in a peer-reviewed journal and presented at six domestic and international scientific conferences.

Academic Significance and Societal Importance of the Research Achievements

The findings of this study suggest that sorbitol-responsive injectable hydrogel may be a novel therapeutic approach for myocardial infarction. Moreover, this study proposes a material concept that may surmount the low retention of cells and drugs to the target tissue.

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2023 2022 2021

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (6 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Prevention of anastomotic stenosis for decellularized vascular grafts using rapamycin-loaded boronic acid-based hydrogels mimicking the perivascular tissue function2023

    • Author(s)
      Le Hue Thi、Mahara Atsushi、Nagasaki Takeshi、Yamaoka Tetsuji
    • Journal Title

      Biomaterials Advances

      Volume: 147 Pages: 213324-213324

    • DOI

      10.1016/j.bioadv.2023.213324

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Challenges of new therapeutic applications for cardiovascular diseases by hydrogel injection2023

    • Author(s)
      Hue Thi Le, Atsushi Mahara, Kyoko Fukazawa, and Tetsuji Yamaoka
    • Journal Title

      Journal of Japanese Society for Biomaterials

      Volume: 41-2 Pages: 114-117

    • Related Report
      2022 Annual Research Report
  • [Presentation] The effect of sorbitol-responsive injectable hydrogel on cardiac function and morphology of MI rat2022

    • Author(s)
      Hue Thi Le
    • Organizer
      The 2022 JSB/SFB Joint Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Perivascular application of rapamycin-loaded hydrogel reduces neointimal hyperplasia in porcine graft transplantation model2022

    • Author(s)
      Hue Thi Le
    • Organizer
      51st Research Group on Biomedical Polymers
    • Related Report
      2022 Annual Research Report
  • [Presentation] Drug-loaded injectable hydrogel with tissue-adhesive ability2022

    • Author(s)
      Hue Thi Le
    • Organizer
      71st SPSJ Symposium on Macromolecules
    • Related Report
      2022 Annual Research Report
  • [Presentation] Sorbitol self-release injetable hydrogel for the treatment of myocardial ischemia2022

    • Author(s)
      Hue Thi Le
    • Organizer
      The 44th annual meeting of Japanese Society for Biomaterials
    • Related Report
      2022 Annual Research Report
  • [Presentation] The effect of sorbitol-responsive injectable hydrogel on cardiac function and morphology of MI rat2022

    • Author(s)
      Hue Thi Le
    • Organizer
      the 2022 JSB/SFB Joint Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of sorbitol-responsive injectable hydrogel for treating myocardial infarction2021

    • Author(s)
      Hue Thi Le
    • Organizer
      The 8th Asian Biomaterial Congress
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-10-22   Modified: 2024-01-30  

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