Irisin-Loaded Physically Cross-linked Silk Fibroin Hydrogel Promotes Muscle Fiber Regeneration in Volumetric Muscle...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Musculoskeletal Research

Background:

• Volumetric muscle loss (VML) presents a significant challenge in musculoskeletal repair, often leading to irreversible motor deficits.
• Current treatments for VML face limitations in promoting comprehensive tissue regeneration and functional recovery.

Purpose of the Study:

• To develop and evaluate a biodegradable silk fibroin (SF) hydrogel as a controlled delivery system for irisin to treat VML.
• To investigate the effects of irisin-loaded SF hydrogels on muscle regeneration and the immune microenvironment in VML models.

Main Methods:

• Fabrication of a biodegradable silk fibroin hydrogel for controlled irisin release.
• In vivo assessment of hydrogel degradation kinetics and irisin release profile.
• Evaluation of muscle regeneration parameters including fiber maturation, alignment, and cross-sectional area (CSA).
• Analysis of satellite cell activation, neuromuscular junction reconstruction, and macrophage polarization (M1 to M2).

Main Results:

• The SF hydrogel exhibited controlled in vivo degradation over 4-6 weeks, synchronizing irisin release with muscle regeneration.
• Irisin-loaded SF hydrogels significantly enhanced muscle fiber maturation, alignment, and CSA.
• Irisin promoted myogenic differentiation, satellite cell activation, and neuromuscular junction repair.
• Irisin induced a shift in macrophage polarization from M1 to M2, increasing IL-10 and TGF-β secretion for enhanced inflammation resolution.

Conclusions:

• This study presents the first demonstration of an irisin delivery strategy using a biodegradable SF hydrogel for VML repair.
• The irisin-loaded SF hydrogel effectively promotes muscle regeneration by modulating both myogenic processes and the immune microenvironment.
• This approach offers a promising therapeutic avenue for clinical applications in treating VML and other muscle injuries.