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

Regenerative rehabilitation can enhance skeletal muscle mass, function, and size following traumatic injuries such as 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 in 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 was continued for 4 weeks. The results showed no improvement in muscle mass or function with combined FBN450 and EST application. Histological analysis revealed reduced type 2B myofiber size and percentage in the combined hydrogel and EST treatment group. Gene expression studies showed increased inflammatory and fibrotic signaling with no concomitant increase in myogenic markers. Collectively, these results indicate that the FBN450 hydrogel therapy did not synergize with EST to improve outcomes following VML.