Advanced Glycation End Products Are Retained in Decellularized Muscle Matrix Derived from Aged Skeletal Muscle

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Aging Research

Background:

• Decellularized tissues are promising biocompatible materials for clinical applications.
• The impact of donor age on the properties of decellularized muscle extracellular matrix is not well understood.
• Advanced glycation end products (AGEs) accumulate with age, increasing collagen stiffness and inflammation.

Purpose of the Study:

• To investigate age-dependent changes in collagen stiffness and AGE cross-linking in decellularized muscle matrix (DMM).
• To determine if AGE accumulation in aged muscle persists after decellularization.
• To assess the efficacy of an AGE cross-link breaker on aged DMM.

Main Methods:

• Characterization of mouse gastrocnemius muscles from 1-, 2-, and 20-month-old mice before and after decellularization.
• Quantification of total and soluble collagen.
• Atomic force microscopy to measure matrix stiffness.
• Assessment of AGE levels and treatment with ALT-711, an AGE cross-link breaker.

Main Results:

• Decellularized muscle matrix (DMM) from older mice exhibited increased collagen content, cross-linking, and stiffness compared to younger sources.
• Aged muscle showed higher levels of AGE-specific cross-links, which were retained in the DMM.
• The AGE cross-link breaker ALT-711 reduced AGE levels in aged DMM, but did not fully reverse age-dependent changes.

Conclusions:

• Age-dependent modifications, including increased collagen cross-linking and stiffness due to AGEs, are present in decellularized muscle extracellular matrix.
• The age of the skeletal muscle source is a critical factor influencing the properties of DMM for biomaterial applications.
• These findings suggest careful consideration of donor age is necessary for the successful clinical translation of decellularized muscle biomaterials.