Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Skeletal Muscle Biology

Background:

• Volumetric muscle loss (VML) can cause irreversible damage to skeletal muscle function.
• Acellular matrices are a promising therapeutic strategy for skeletal muscle regeneration.
• Investigating decellularized scaffolds for VML treatment is crucial.

Purpose of the Study:

• To evaluate the efficacy of three decellularized skeletal muscle scaffolds in promoting muscle regeneration following VML.
• To compare the regenerative potential of scaffolds based on extracellular matrix (ECM) versus those preserving cytoskeletal structures.
• To elucidate the role of fibroblasts in muscle stem cell migration and myogenesis within scaffolds.

Main Methods:

• Surgical resection of the EDL muscle in a xenogeneic immune-competent VML model.
• Implantation of three different decellularized skeletal muscle scaffolds.
• Assessment of host myogenic cell migration, differentiation, nerve and vascular network formation, and satellite cell (SC) homing.
• In vitro studies on fibroblast-mediated muscle stem cell migration and myogenesis.

Main Results:

• All implanted acellular matrices supported the formation of functional artificial muscles.
• Scaffolds primarily composed of ECM demonstrated superior myofiber 3D organization and SC pool restoration compared to those preserving cytoskeletal structures.
• Fibroblasts were found to be essential for promoting efficient migration and myogenesis of muscle stem cells in vitro.

Conclusions:

• Xenogeneic acellular muscle scaffolds are effective devices for treating VML without requiring donor cell transplantation.
• ECM-rich scaffolds offer advantages for myofiber organization and satellite cell restoration in VML regeneration.
• These findings establish acellular muscle scaffolds as valuable in vitro models for studying myogenesis and cell interactions.