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Interlinked Macroporous 3D Scaffolds from Microgel Rods

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Dynamic Macropore Formation via Dual-Degrading Injectable Microgels Enhances Host-Mediated Angiogenesis and

Jiayuan Kong^1,2,3, Hexiang Feng^2,3,4, Minh Phan⁵

¹Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

Advanced Healthcare Materials

|September 4, 2025

Summary

This study introduces a novel injectable hyaluronic acid (HA) macroporous hydrogel that enhances tissue regeneration. The dual-degrading microgel system promotes cell infiltration and integration for improved soft tissue repair.

Keywords:

angiogenesis degradable biomaterials dynamic hydrogels macropore formation regenerative medicine

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Published on: September 7, 2017

Area of Science:

Biomaterials Science
Tissue Engineering
Regenerative Medicine

Background:

Hydrogels are crucial in tissue engineering but dense networks hinder cell infiltration.
Granular hydrogels improve integration but lose porosity in vivo.
Existing hydrogels face challenges in balancing cell infiltration and structural integrity.

Purpose of the Study:

To design an injectable hyaluronic acid (HA) macroporous hydrogel with tunable degradation profiles.
To enhance cell infiltration and tissue integration for soft tissue regeneration.
To investigate the role of microgel ratio and host cell response in hydrogel performance.

Main Methods:

Formulation of an injectable HA hydrogel mixture using two microgels with differential degradation rates.
Computational simulations to optimize the microgel ratio for maximal cell infiltration.
In vivo studies in rats to assess hydrogel performance, macrophage response, and angiogenesis.

Main Results:

A 1:1 volume ratio of faster- and slower-degrading HA microgels maximized host cell infiltration.
The faster-degrading HA component induced pro-regenerative macrophage phenotypes and enhanced angiogenesis.
The dual-degrading system enabled gradual pore formation while maintaining structural integrity via host cell ECM deposition.

Conclusions:

Programmable macroporous hydrogel design effectively modulates host cell infiltration and tissue integration.
This dual-degrading microgel system offers a promising strategy for soft tissue regeneration.
The hydrogel's ability to recruit and modulate immune cells is critical for its regenerative capacity.