Meniscal extracellular matrix remodelling caused by injuries and degeneration

• Multimodal analysis on degenerative, traumatic, and pediatric menisci can reveals ECM composition as driving actor in fucntional alterations • Age-dependent ECM composition has direct impact on morphological and functional differences of menisci • In deepth correlations of mechanical and chemical composition of ECM can highlight determinants of meniscal integrity and repair potential. The characterization of meniscal extracellular matrix (ECM) is fundamental for tissue engineering to design a functional substitute. However, most of the available data come from animal studies. The meniscus has a complex ECM, characterized by a specific orientation of collagen fibres related to its function. In this work, both pediatric and adult meniscal tissues were examined from morphological, biochemical, and mechanical perspectives to identify the characteristics of physiological tissue and the changes caused by injuries and degeneration. Additionally, a comparison was performed between menisci from patients with normal and valgus knees to observe ECM remodeling associated with altered biomechanics. Obtained results indicatet that, with both aging and pathology, collagen and glycosaminoglycans (GAG) content decreased, while mucins increased. These changes were accompanied by alterations in tissue structure at both the macroscopic and nanoscale levels, including less organized collagen networks and thicker, more fibrotic fibres. Correspondingly, the elastic modulus decreased with age, reflecting a loss of tissue mechanical integrity. The various results from the morphological, biochemical, and mechanical analyses were then correlated in a qualitative and descriptive manner to provide a comprehensive impression of tissue organization and remodelling. Finally, the obtained results were compared with data available in the literature to highlight similarities and differences between humans of various ages and animal models.