Skeletal muscle fibrosis: the effect of stromal-derived factor-1α-loaded collagen scaffolds

Aim: To develop a model for muscle fibrosis based on full-thickness muscle defects, and to evaluate the effects of implanted stromal-derived factor (SDF)-1 alpha-loaded collagen scaffolds. Methods: Full-thickness defects 2 mm in diameter were made in the musculus soleus of 48 rats and either left alone or filled with SDF-1 alpha-loaded collagen scaffolds. At 3, 10, 28 and 56 days postsurgery, muscles were analyzed for collagen deposition, satellite cells, myofibroblasts and macrophages. Results: A significant amount of collagen-rich fibrotic tissue was formed, which persisted over time. Increased numbers of satellite cells were present around, but not within, the wounds. Satellite cells were further upregulated in regenerating tissue when SDF-1 alpha-loaded collagen scaffolds were implanted. The scaffolds also attracted macrophages, but collagen deposition and myofibroblast numbers were not affected. Conclusion: Persistent muscle fibrosis is induced by full-thickness defects 2 mm in diameter. SDF-1 alpha-loaded collagen scaffolds accelerated muscle regeneration around the wounds, but did not reduce muscle fibrosis.