2. Academic Validation
  3. Enhanced Tissue Regeneration Through Immunomodulatory Extracellular Vesicles Encapsulated in Diversified Silk-Based Injectable Hydrogels

Enhanced Tissue Regeneration Through Immunomodulatory Extracellular Vesicles Encapsulated in Diversified Silk-Based Injectable Hydrogels

  • Adv Healthc Mater. 2024 Jul 16:e2401460. doi: 10.1002/adhm.202401460.
Liangyan Sun 1 2,  Menglin Xiao 1 3,  Ling Chen 1 3,  Lingyue Ni 1 2,  Xiaoxuan Chen 1 2,  Lina Zhang 4,  Jinrong Yao 1 3,  Zhengzhong Shao 1 3,  Bingjiao Zhao 1 2,  Xin Chen 1 3,  Yuehua Liu 1 2
Affiliations

Affiliations

  • 1 Department of Orthodontics, Department of Macromolecular Science, Multidisciplinary Consultant Center, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200001, China.
  • 2 Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
  • 3 State Key Laboratory of Molecular Engineering of Polymers, Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, China.
  • 4 Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
PMID: 39011805 DOI: 10.1002/adhm.202401460
Abstract

Mesenchymal stem cells (MSCs) immunologically trained using lipopolysaccharide (LPS) display enhanced immunomodulatory capabilities. Extracellular vesicles (EVs) derived from MSCs are widely used in regenerative medicine owing to their bioactive properties without the drawbacks of cell therapy. However, it remains unclear whether EVs derived from LPS-stimulated (trained) MSCs (L-EVs) inherit the enhanced reparative potential from their parent cells. Thus, this study first aims to explore the effect of immunological training on the bioactivity of L-EVs. LPS-trained bone marrow-derived MSCs (BMSCs) secrete more EVs, and these EVs significantly promote M2 macrophage polarization. Subsequently, hydrogel systems based on thixotropic injectable silk fibroin are prepared for in vivo EV delivery. These hydrogels have controllable gelation time and exhibit outstanding reparative effects on rat skin wounds and alveolar bone defects. Finally, it is revealed that L-EVs promote M2 macrophage polarization by inhibiting the nuclear translocation of PKM2. Overall, this study shows that the immunological training of BMSCs effectively improves the therapeutic effects of their EVs and provides a convenient and diversified EV delivery strategy using an injectable silk fibroin hydrogel. This strategy has broad clinical application prospects for tissue regeneration.

Keywords

extracellular vesicles (EVs); hydrogels; macrophage polarization; regeneration; silk fibroin.

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