Abstract
Decellularized tissues are biocompatible materials that engraft well, but the age of their source has not been explored for clinical translation. Advanced glycation end products (AGEs) are chemical cross-links that accrue on skeletal muscle collagen in old age, stiffening the matrix and increasing inflammation. Whether decellularized biomaterials derived from aged muscle would suffer from increased AGE collagen cross-links is unknown. We characterized gastrocnemii of 1-, 2-, and 20-month-old C57BL/6J mice before and after decellularization to determine age-dependent changes to collagen stiffness and AGE cross-linking. Total and soluble collagen was measured to assess if age-dependent increases in collagen and cross-linking persisted in decellularized muscle matrix (DMM). Stiffness of aged DMM was determined using atomic force microscopy. AGE levels and the effect of an AGE cross-link breaker, ALT-711, were tested in DMM samples. Our results show that age-dependent increases in collagen amount, cross-linking, and general stiffness were observed in DMM. Notably, we measured increased AGE-specific cross-links within old muscle, and observed that old DMM retained AGE cross-links using ALT-711 to reduce AGE levels. In conclusion, deleterious age-dependent modifications to collagen are present in DMM from old muscle, implying that age matters when sourcing skeletal muscle extracellular matrix as a biomaterial.
Highlights
Musculoskeletal aging in individuals over 65 years impacts independence, increases the risk of fall-related injuries, and reduces life quality [1]
Nuclei were counted in all samples, and we determined there to be a reduction in the number of total nuclei with age
We explore the age-dependent changes in collagen cross-linking, we used hydroxyproline-based measured porosity in decellularized muscle matrix (DMM) and did not observe any age‐dependent differences
Summary
Musculoskeletal aging in individuals over 65 years impacts independence, increases the risk of fall-related injuries, and reduces life quality [1]. The deterioration of muscle’s strength and mass with increasing age culminates in a condition known as sarcopenia, an age-dependent muscle wasting disease [2,3,4,5,6,7]. Advanced glycation end products (AGEs), the final derivative of the Maillard or browning reaction, are known to accumulate in musculoskeletal tissues in old age and are thought to play a role in the development of sarcopenia [8,9,10]. In addition to having a long half-life, collagens are rich in repeating arginine and lysine amino acids that potentiate the reaction between collagen and AGE precursors, further predisposing collagen to these glycation cross-links [11].
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