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Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation

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An engineering-reinforced extracellular vesicle-integrated hydrogel with an ROS-responsive release pattern mitigates

Jian Cao¹, Xunqi Zhang¹, Jing Guo¹

¹State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Science Advances

|April 2, 2025

Summary

Engineered extracellular vesicles (EVs) delivered via hydrogel enhance spinal cord injury (SCI) recovery. This novel hydrogel system allows for controlled, on-demand release of therapeutic EVs, improving treatment efficacy for central nervous system injuries.

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The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

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Area of Science:

Biomaterials Science
Regenerative Medicine
Neuroscience

Background:

Local delivery of mesenchymal stem cell-derived extracellular vesicles (EVs) via hydrogel shows promise for spinal cord injury (SCI) treatment.
Current hydrogel systems face challenges in achieving on-demand release of EVs to match dynamic pathological changes.

Purpose of the Study:

To enhance the efficacy of EVs and optimize their release kinetics from hydrogel for SCI treatment.
To develop a reactive oxygen species (ROS)-responsive hydrogel system for controlled EV delivery.

Main Methods:

EVs were enhanced through 3D culture and dexamethasone (Dxm) encapsulation to boost pro-angiogenic, neurotrophic, and anti-inflammatory effects.
Dxm-loaded EVs (3EVs-Dxm) were modified with ortho-dihydroxy groups and integrated into a hydrogel (3EVs-Dxm-Gel) using phenylboronic acid-modified hyaluronic acid and tannic acid.
The hydrogel utilized phenylboronic acid ester linkages for EV immobilization and ROS-responsive release.

Main Results:

The engineered hydrogel system successfully immobilized and enabled ROS-responsive release of EVs.
Topical injection of the 3EVs-Dxm-Gel in SCI rat models significantly reduced injury severity.
Promoted functional recovery in SCI rats, indicating enhanced therapeutic outcomes.

Conclusions:

The developed EV-integrated hydrogel system offers an effective strategy for on-demand delivery of therapeutic EVs.
This approach holds potential for advancing EV-based therapies for central nervous system injuries like SCI.