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IVD herniation involves cellular and extracellular matrix (ECM) alterations that have been associated with tissue fibrosis, although still poorly investigated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Here, fibrotic alterations in human AF were evaluated, by characterizing the herniated ECM. Human AF samples (herniated lumbar IVD (<jats:italic>n<\/jats:italic> = 39, age 24\u201383) and scoliosis controls (<jats:italic>n<\/jats:italic> = 6, age 15\u201321)) were processed for transmission electron microscopy and histological\/immunohistochemical analysis of fibrotic markers. Correlations between the fibrotic markers in AF ECM and the degree of NP containment (protused, contained and uncontained) and patients\u2019 age were conducted.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our results demonstrate that with herniation progression, i.e. loss of NP containment, human AF presents less stained area of sulphated glycosaminoglycans and collagen I, being collagen I fibres thinner and disorganized. On the other hand, fibronectin stained area and percentage of \u03b1-smooth muscle actin+ cells increase in human AF, while matrix metalloproteinase-12 (MMP12) production and percentage of macrophages (CD68+ cells) remain constant. These structural and biochemical fibrotic alterations observed in human AF with herniation progression occur independently of the age.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The characterization of human AF here conducted evidence the presence of fibrosis in degenerated IVD, while highlighting the importance of considering the herniation progression stage, despite the patients\u2019 age, for a better understanding of the mechanisms behind AF failure and IVD herniation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-021-02690-w","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T09:04:50Z","timestamp":1642410290000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation"],"prefix":"10.1186","volume":"24","author":[{"given":"A. 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