Repairing Volumetric Muscle Loss with Skeletal Muscle Units and Hyaluronic Acid Hydrogel in Rats

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Muscle Physiology

Background:

• Volumetric muscle loss (VML) exceeds self-repair, leading to incomplete functional recovery and potential fibrosis.
• Current treatments like grafts have limitations, including tissue availability and donor site morbidity.
• Hydrogels are emerging therapeutics with potential to reduce fibrosis and improve muscle regeneration.

Purpose of the Study:

• To evaluate the therapeutic potential of engineered skeletal muscle units (SMUs) alone and with hyaluronic acid-based hydrogel (HyA-HG) for VML repair.
• To assess the impact of SMU and HyA-HG combination therapy on muscle structure and function post-VML injury.
• To investigate the short-term and long-term effects of the combination therapy on muscle regeneration and fibrosis.

Main Methods:

• A 30% VML injury was created in the rat tibialis anterior muscle.
• Repairs were performed using SMUs alone, or SMUs combined with HyA-HG.
• Muscle structure and function were assessed at 1 and 3 months post-implantation via histological analysis and force production measurements.

Main Results:

• The combination of HyA-HG and SMUs improved force production at 1 month post-VML repair.
• Sustained superior improvements in muscle function were not observed at 3 months compared to SMU-only repair.
• Histological analysis showed increased cross-sectional area and force production in the early recovery stage (1 month) with SMU and HyA-HG treatment.

Conclusions:

• SMU and HyA-HG combination therapy demonstrates potential for enhancing early functional recovery following VML.
• The benefits of the combination therapy appear transient, with comparable outcomes across groups at 3 months.
• Further research is warranted to optimize hydrogel-based strategies for long-term VML functional restoration.