期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms22168832
关键词
skeletal muscle aging; decellularization; advanced glycation end products; collagen cross-linking
资金
- National Science Foundation CMMI [1351162]
- Department of Defense DMRDP [W81XWH-18-10352]
- Musculoskeletal Transplant Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1351162] Funding Source: National Science Foundation
Decellularized tissues derived from aged sources exhibit age-dependent increases in collagen amount, cross-linking, and stiffness. This suggests that age is an important factor to consider when sourcing skeletal muscle extracellular matrix as a biomaterial.
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.
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