Comparison of annulus fibrosus tissue from tails of neonatal mice aged postnatal day 5, day 14, day 21, and day 28

Neonatal mouse intervertebral discs lose regenerative potential between postnatal day 14 and day 28during a period of Intervertebral disc (IVD) defects heal poorly and can cause back pain and disability. We identified that IVD herniation injury heals regeneratively in neonatal mice until postnatal day 14 (p14) and shifts to fibrotic healing by p28. This age coincides with the shift in expansive IVD growth from cell proliferation to matrix elaboration, implicating collagen crosslinking. -aminopropionitrile treatment reduced IVD crosslinking and caused fibrotic healing without affecting cell proliferation. Bulk sequencing on naïve IVDs were depleted for matrix structural organization from p14 to p28 to validating the importance of crosslinking in regenerative healing. We conclude that matrix changes are key drivers in the shift to fibrotic healing, and a stably crosslinked matrix is needed for IVD regeneration.