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Off-the-Shelf Granular Microtissue Bioinks: Long-Term Preserved Cellularized Porous Microgels with Enhanced Cell

Chuqian Wang1,2, Ziyu Wang1,3, Yiyang Lin4

  • 1Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111Base), Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

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Summary

This study presents an optimized cryo-gelation method for creating cellularized microtissues. These off-the-shelf products enable long-term preservation and on-demand use in regenerative medicine, improving tissue growth and function.

Keywords:
biofabricationcell‐laden microgelshydrogelsinterfacespreservation

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Achieving long-term preservation and superior biological outcomes for off-the-shelf cellularized products in tissue engineering remains a challenge.
  • Current methods often require on-site cell isolation and preparation, limiting accessibility and on-demand application.

Purpose of the Study:

  • To develop a cellularized porous microgel platform using optimized cryo-gelation for long-term cryopreservation.
  • To create modular, injectable, and printable microtissues that enhance cell growth and function.
  • To demonstrate the therapeutic potential of these ready-to-use cellularized blocks for tissue regeneration.

Main Methods:

  • Optimization of cryo-gelation methodology to create cellularized porous microgels.
  • Development of modular granular microtissues as injectable formulations and printable bioinks.
  • Assessment of long-term cryopreservation stability (up to 14 months).
  • Evaluation of cell growth and function enhancement due to internal biomaterial interfaces.
  • In vivo testing through subcutaneous injection and repair of critical-sized skull defects in rats.

Main Results:

  • The developed microgel platform allows for shelf cryopreservation of cellularized products for up to 14 months.
  • Subvoxel interfaces within the microtissues significantly enhance cell growth and function compared to conventional bulk materials.
  • The modular microtissues demonstrated successful application in subcutaneous injection and critical-sized skull defect repair in rats.
  • The ready-to-use, cell-laden modules proved effective for on-demand regenerative medicine applications.

Conclusions:

  • Optimized cryo-gelation yields a stable, off-the-shelf cellularized microgel platform for tissue engineering.
  • The platform's modularity and enhanced internal interfaces promote superior cell behavior and tissue regeneration.
  • These findings enable highly accessible and on-demand cell-based regenerative therapies.