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Quantifying Three-Dimensional Cell Migration Within and Into Granular Hydrogel Biomaterials
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A Balance between Inter- and Intra-Microgel Mechanics Governs Stem Cell Viability in Injectable Dynamic Granular

Cameron D Morley1, Erika A Ding2, Emily M Carvalho2

  • 1Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.

Advanced Materials (Deerfield Beach, Fla.)
|September 1, 2023
PubMed
Summary

This study introduces injectable microgels for cell delivery, independently tuning elasticity and flowability. This innovation enhances cell protection during injection and improves formulation development for tissue engineering applications.

Keywords:
3D bioprintingadamantane and cyclodextrininjectable granular hydrogelsmicrogelsyield stress materials

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Drug Delivery

Background:

  • Injectable hydrogels are crucial for delivering cells to tissues, offering mechanical protection and a stable niche.
  • Current methods often alter elasticity and flowability simultaneously, creating a trade-off between injectability and stability.
  • Independent control over these properties is needed for advanced formulation development.

Purpose of the Study:

  • To develop a novel strategy for independently tuning the mechanical properties of injectable hydrogels for cell delivery.
  • To investigate the relationship between microgel properties and injectability.
  • To enhance cell protection during the injection process.

Main Methods:

  • Cells were encapsulated within hyaluronic acid (HA) microgels.
  • Intra-microgel crosslinks controlled elasticity, while adamantane-cyclodextrin (AC) inter-microgel crosslinks modulated flowability.
  • A 3D printing support bath using AC-free microgels preserved cell location during injection.

Main Results:

  • A method was established to independently tune microgel elasticity and flowability.
  • The study identified the injectability threshold based on microgel yielding and AC interactions.
  • Optimized microgel formulations demonstrated improved injection-protecting performance for cells.

Conclusions:

  • This microgel system allows independent tuning of elasticity and flowability, overcoming limitations of current injectable hydrogels.
  • The findings provide insights into the mechanisms of mechanical trauma during cell injection.
  • This approach facilitates the development of advanced injectable formulations for cell therapy and tissue engineering.