Neonatal mouse intervertebral discs heal with restored function following herniation injury

Adult intervertebral discs (IVDs) have poor endogenous healing capacity, because of their challenging microenvironment and complex mechanical demands, which can result in painful IVD herniation. There are no regenerative strategies available to improve IVD healing and restore its function. Neonatal mice are excellent models of mammalian regeneration, but there are no studies of the regenerative capacity of neonatal IVDs. In this study, we developed a neonatal model of improved IVD healing to inform repair strategies after herniation. In vivo puncture injuries were performed to simulate herniation with complete annulus fibrosus (AF) tears in caudal IVDs of neonatal (postnatal d 5) and adult (4-6 mo) Scleraxis green fluorescent protein (ScxGFP) mice. Acute and long-term healing responses were assessed with histologic, radiologic, and biomechanical measurements. Neonates underwent accelerated IVD healing compared to adults with functional restoration and enhanced structural repair after herniation. A population of ScxGFP(-) cells identified in the neonatal repair site may be associated with this improved healing and warrants future investigation. In summary, function of neonatal IVDs was restored after herniation injury, whereas that of adult discs was not. This improved healing response is likely driven by multiple mechanisms that may include differences in mechanical loading and available repair cells during growth.Torre, O. M., Das, R., Berenblum, R. E., Huang, A. H., Iatridis, J. C. Neonatal mouse intervertebral discs heal with restored function following herniation injury.