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In Vivo Functional Assessment of Rat Masseter Muscle Following Surgical Creation of a Volumetric Muscle Loss (VML) Injury
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Repairing Volumetric Muscle Loss with Commercially Available Hydrogels in an Ovine Model
Eileen Y Su1, Christopher S Kennedy1, Emmanuel E Vega-Soto1
1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Tissue Engineering. Part A
|December 20, 2023
Summary
Hyaluronic acid hydrogels combined with engineered muscle units effectively treat volumetric muscle loss in sheep. This approach reduces inflammation and fibrosis, promoting muscle regeneration for potential human therapies.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Skeletal Muscle Biology
Background:
- Volumetric muscle loss (VML) causes permanent functional deficits due to exceeding the muscle's self-repair capacity.
- Previous studies showed tissue-engineered skeletal muscle units (SMUs) restore muscle mass but fibrosis hinders full recovery.
- Hydrogels (HGs) show potential to reduce inflammation and fibrosis, enhancing skeletal muscle regeneration after VML.
Purpose of the Study:
- To assess the biocompatibility of poly(ethylene glycol), methacrylated gelatin, and hyaluronic acid (HA) hydrogels with SMUs for VML treatment.
- To evaluate the efficacy of combining HGs with SMUs in a large animal model for VML repair.
- To determine the optimal HG for combination therapy based on reduced inflammation and enhanced regeneration.
Main Methods:
- A 30% VML injury was created in sheep peroneus tertius (PT) muscles.
- Muscles were repaired with or without different HGs (poly(ethylene glycol), methacrylated gelatin, HA) and SMUs.
- Acute inflammation was assessed via swelling and white blood cell counts; structural recovery and fibrosis were evaluated histologically after 6 weeks.
Main Results:
- Hyaluronic acid (HA) hydrogel demonstrated reduced acute inflammation compared to other tested HGs.
- SMU-only and SMU+HA groups restored muscle mass significantly, with masses indistinguishable from the uninjured contralateral muscle.
- HA hydrogel, SMU-only, and SMU+HA groups showed reduced pro-inflammatory markers and increased regenerating muscle fibers.
Conclusions:
- HA hydrogels are biocompatible and effectively decrease acute inflammation and fibrotic response in VML repair.
- Combining HA hydrogels with SMUs holds promise for treating VML by reducing inflammation and fibrosis while promoting muscle regeneration.
- This combination therapy represents a potential advancement towards clinical interventions for human VML injuries.
