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Related Experiment Video

Updated: Sep 30, 2025

Capillary-based Centrifugal Microfluidic Device for Size-controllable Formation of Monodisperse Microdroplets
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Heterogeneous spheroids with tunable interior morphologies by droplet-based microfluidics.

Zhen Zhan1, Zeyang Liu1, Haochen Nan1

  • 1Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China.

Biofabrication
|March 15, 2022
PubMed
Summary

Researchers developed a microfluidic device to create complex 3D spheroids with tunable internal structures. This innovation enables the fabrication of intricate tissue constructs with potential applications in regenerative medicine.

Keywords:
heterogeneous spheroidsmicroenvironmentsmicrofluidicstissue engineeringviscous instability

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Last Updated: Sep 30, 2025

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Area of Science:

  • Biomaterials Engineering
  • Microfluidics
  • Tissue Engineering

Background:

  • Heterogeneous spheroids are crucial for mimicking natural tissue complexity in biomedical applications.
  • Existing methods struggle with precise control over spheroid interior morphology due to limited spatial resolution.
  • Geometric cues within the cellular matrix significantly influence cell behavior and phenotype.

Purpose of the Study:

  • To develop a microfluidic approach for fabricating spheroids with tunable dimensions and complex interior morphologies.
  • To investigate the role of fluid dynamics in creating diverse internal structures within hydrogel microspheres.
  • To demonstrate the potential of these engineered spheroids for constructing functional tissue constructs.

Main Methods:

  • A coaxial capillary microfluidic device was utilized to manipulate two-phase flow of gelatin methacrylate (GelMA) and methylcellulose solutions.
  • Interacting viscous instabilities in the two-phase flow, followed by emulsion and photopolymerization, generated diverse interior morphologies (core-shell, wavy, spiral).
  • Polyethylene glycol diacrylate (PEGDA) was incorporated to modulate mechanical properties, with optimal concentration determined via *in vitro* cell studies.

Main Results:

  • The microfluidic system successfully generated GelMA microspheres with controllable dimensions and intricate internal structures, including spiral canals.
  • Incorporation of PEGDA allowed for tuning of microsphere mechanical properties.
  • Optimized PEGDA concentration supported *in vitro* proliferation and vascularization of human umbilical vein endothelial cells.
  • A heterogeneous spheroid with a spiral blood vessel lumen was successfully constructed.

Conclusions:

  • The developed droplet-based microfluidic approach offers precise control over spheroid interior morphology, overcoming previous limitations.
  • This method provides a versatile platform for creating advanced, heterogeneous tissue constructs with biomimetic features.
  • The engineered spheroids hold significant promise for applications in tissue engineering and regenerative medicine.