Application of Fibrin-Laminin Hydrogel Concurrent with Electrically Stimulated Eccentric Training Hinders Recovery in Volumetric Muscle Loss

Regenerative rehabilitation can enhance skeletal muscle recovery following trauma-induced volumetric muscle loss (VML). We previously optimized fibrin-laminin hydrogels for muscle regeneration and an electrically stimulated eccentric contraction training (EST) for muscle rehabilitation. The goal of this study was to examine the combined effect of these two therapies on maximizing tissue recovery. A VML defect was created by removing ~20% of muscle mass from the tibialis anterior (TA) muscle in adult male Lewis rats. The injured TA muscles were treated with fibrin-laminin (FBN450) hydrogel. EST was implemented 2 weeks post-injury at both 100 Hz and 150 Hz frequencies and continued for 4 weeks. The results showed no improvement in muscle mass or function with combined FBN450 and EST application. Histological analysis revealed significantly reduced type 2B myofiber cross-sectional area (CSA) and percentage in the combined hydrogel and EST treatment group. Gene expression studies showed >20-fold higher inflammatory (e.g., CCR7, CD163) and fibrotic (e.g., Col1a1) signaling, with no concomitant increase in myogenic markers in the hydrogel + EST group. Collectively, these results indicate that the FBN450 hydrogel therapy did not synergize with EST to improve outcomes following VML.