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Bioactive Hydrogel Supplemented with Stromal Cell-Derived Extracellular Vesicles Enhance Wound Healing
Matteo Galbiati1, Fabio Maiullari1,2, Maria Grazia Ceraolo3
1Institute for Biomedical Technologies, National Research Council, Via Fratelli Cervi, 93, Segrate, 20054 Milan, Italy.
Pharmaceutics
|February 26, 2025
Summary
This study developed a novel hydrogel using fibroblast-derived extracellular vesicles (EVs) to significantly accelerate skin wound healing. The optimized method enhances EV stability for potential clinical applications in regenerative medicine.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Tissue Engineering
Background:
- Skin regeneration is crucial for treating wounds and burns, with significant implications for regenerative medicine.
- Fibroblast-derived extracellular vesicles (EVs) offer immunoprivileged properties, minimizing immune rejection and replicating fibroblast roles in tissue repair.
- Developing stable and effective delivery systems for EVs is essential for their clinical application.
Purpose of the Study:
- To explore the potential of hydrogels functionalized with fibroblast-derived EVs for enhancing skin regeneration in vivo.
- To optimize a lyophilization method for preserving EV stability and bioactivity.
- To evaluate the efficacy of EV-functionalized hydrogels in accelerating wound healing in a murine model.
Main Methods:
- Optimized a lyophilization method with lyoprotectants for fibroblast-derived EVs.
- Functionalized Gelatin methacrylate (GelMA) hydrogels with the preserved EVs.
- Characterized EVs (Western blot, TEM, NanoSight) and analyzed their miRNome.
- Evaluated hydrogel efficacy in murine cutaneous wound models.
Main Results:
- GelMA hydrogels demonstrated suitable mechanical properties for wound healing applications.
- Characterization confirmed EV integrity, stability, and identified key biological pathways (migration, differentiation, angiogenesis).
- Hydrogels loaded with fibroblast-derived EVs significantly accelerated wound healing in mice, showing faster closure, enhanced epithelialization, increased vascularization, and reduced fibrosis.
- Lyophilization successfully preserved EV structure and bioactivity, reducing EV loss by 35%.
Conclusions:
- A novel, scalable strategy combining fibroblast-derived EVs with GelMA hydrogels enhances wound healing.
- Optimized lyophilization ensures EV stability and functionality for potential long-term storage and clinical use.
- This approach holds promise for advanced regenerative medicine, particularly for large-scale wound treatment scenarios.
