Simultaneous Effect of High Intensity Interval Training and Human Amniotic Membrane Scaffold on Rat Tibialis Anterior Vascularization and Innervation after Volumetric Muscle Loss Injury

Abstract

Background: Despite the high regenerative capacity of skeletal muscle, volumetric muscle loss (VML) is an irrecoverable injury. One therapeutic approach is the implantation of engineered biologic scaffolds.

Objective: To investigate the simultaneous effect of high intensity interval training (HIIT) and the use of decellularized human amniotic membrane (dHAM) scaffolds on vascularization, growth factor, and neurotrophic factor gene expression, and muscle force generation in the tibialis anterior (TA) of rats after VML injury.

Methods: VML injury was created in the TA of 24 rats, which were randomly divided into two groups—12 animals with and 12 without the use of a dHAM scaffold. After injury, each group was further divided into two groups of 6 animals each—sedentary and HIIT. Blood vessels were visualized and counted by hematoxylin and eosin staining. The PowerLab converter assay was used to evaluate isometric contraction force. The relative expression of neurotrophic factors and growth factor genes was measured with reverse transcription PCR (RT-PCR).

Results: The number of blood vessels in the whole regenerating areas showed a significant difference in the dHAM-HIIT and dHAM-sedentary groups compared to the sedentary group without dHAM (p=0.001 and p=0.003, respectively). BDNF and GDNF mRNA levels in the dHAM-HIIT group were significantly (p<0.05) higher than those in other groups; NGF mRNA levels did not differ significantly among groups. Isometric contraction force in the dHAM-HIIT group was significantly (p=0.001) greater compared to the sedentary group without dHAM.

Conclusion: Combined use of dHAM scaffoldsand HIIT would improve the structure of the injured muscle during regeneration after VML by better vascular perfusion. HIIT leads to greater force generation and innervation by modulating neurotrophic factor synthesis in regenerating muscles.