Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Muscle Physiology

Background:

• Muscle atrophy, including sarcopenia, significantly impairs health and increases mortality.
• Current treatments like exercise and nutrition are limited, and cell/drug therapies face challenges.
• Cell-free extracellular matrix (ECM) holds promise but requires improved mechanical and adhesive properties.

Purpose of the Study:

• To develop durable muscle ECM (MEM) hydrogels fortified with phenolic moieties (catechol, pyrogallol).
• To evaluate the enhanced mechanical and adhesive properties of these phenolic MEM hydrogels.
• To assess the efficacy of cell-free phenolic MEM hydrogels in treating muscle atrophy.

Main Methods:

• Fortification of muscle ECM with catechol and pyrogallol to create phenolic MEM hydrogels.
• Characterization of hydrogel mechanical strength and adhesive properties.
• In vivo injection of phenolic MEM hydrogels into mouse models of disuse- and age-induced muscle atrophy.
• Assessment of local and systemic toxicity, muscle protein synthesis, and functional recovery.

Main Results:

• Phenolic MEM hydrogels demonstrated significantly enhanced mechanical and adhesive characteristics.
• No local or systemic toxicities were observed post-injection.
• Cell-free hydrogels promoted muscle protein synthesis and facilitated significant functional muscle recovery.
• Tissue rejuvenation and reversal of muscle loss were observed in atrophy models.

Conclusions:

• Cell-free, ECM-based therapeutics using fortified MEM hydrogels offer a promising strategy for muscle atrophy.
• This approach enhances muscle regeneration and functional recovery without cells or drugs.
• Phenolic MEM hydrogels present a translational therapeutic potential for combating muscle loss and disability.