Regenerative therapies for intervertebral disc degeneration: A translational approach to serve man and dog

Abstract

Low back pain is a common type of pain restricting daily activity in man and dogs. Degeneration of the intervertebral disc (IVD), is strongly associated with back pain. Patients with late stage IVD disease and pain refractory to medication can only be surgically treated. Such surgical treatments demand an extended period of revalidation but do not lead to full recovery. Therefore, the aim of this thesis was to develop innovative treatments to regenerate early degenerated IVDs in order to treat back pain and regain disc function. First of all safety of intradiscal injection was shown in a canine model predisposed for IVD degeneration. In contrast to the regenerative effects of the growth factor rhBMP-7 in vitro in canine IVD cells, intradiscal injection in vivo in a canine model showed no regeneration of the IVD, but extensive extradiscal new bone formation. Biomaterials loaded with bioactive substances could function as local sustained release systems and thereby provide a solution to this problem. Hence, safety and biocompatibility of injectable microspheres and a thermoreversible hydrogel were investigated and demonstrated in the previously mentioned canine model. Intradiscal application of sustained release of the anti-inflammatory drug celecoxib, to decrease levels of the inflammatory mediator PGE2, seemed most beneficial in dogs with clinical signs of IVD degeneration. In canine patients with late stage IVD disease surgical stabilization of the spinal segment is indicated, and can be provided by pedicle screw-rod fixation (PSRF). A good long term clinical outcome of PSRF was described in 12 client-owned dogs with back pain due to severe degenerative lumbosacral IVD disease. Subsequently, PSRF in combination with temporary distraction, thereby unloading the IVD, was applied in a dog with mild clinical signs of back pain related to IVD degeneration. Although the dog improved from a clinical perspective, it remains to be determined whether temporary distraction of a spinal segment results in regeneration and restoration of IVD function.