Microfluidic templating of spatially inhomogeneous protein microgels

Yufan Xu, Raphaël P.B. Jacquat, Yi Shen, Daniele Vigolo, David Morse, Shuyuan Zhang, Tuomas P.J. Knowles*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
185 Downloads (Pure)


3D scaffolds in the form of hydrogels and microgels have allowed for more native cell-culture systems to be developed relative to flat substrates. Native biological tissues are, however, usually spatially inhomogeneous and anisotropic, but regulating the spatial density of hydrogels at the microscale to mimic this inhomogeneity has been challenging to achieve. Moreover, the development of biocompatible synthesis approaches for protein-based microgels remains challenging, and typical gelation conditions include UV light, extreme pH, extreme temperature, or organic solvents, factors which can compromise the viability of cells. This study addresses these challenges by demonstrating an approach to fabricate protein microgels with controllable radial density through microfluidic mixing and physical and enzymatic crosslinking of gelatin precursor molecules. Microgels with a higher density in their cores and microgels with a higher density in their shells are demonstrated. The microgels have robust stability at 37 °C and different dissolution rates through enzymolysis, which can be further used for gradient scaffolds for 3D cell culture, enabling controlled degradability, and the release of biomolecules. The design principles of the microgels could also be exploited to generate other soft materials for applications ranging from novel protein-only micro reactors to soft robots.

Original languageEnglish
Article number2000432
Pages (from-to)1-9
Number of pages9
Issue number32
Early online date11 Jun 2020
Publication statusPublished - 13 Aug 2020


  • enzymatic crosslinking
  • gelatin
  • microfluidic mixing
  • microgels
  • physical crosslinking
  • radial density

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • General Chemistry
  • General Materials Science


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