Biomechanical and in vivo evaluation of experimental closure devices of the annulus fibrosus designed for a goat nucleus replacement model

Promising strategies are being developed to replace or regenerate the herniated nucleus pulposus. However, clinical efficacy of these methods has still to be addressed, and the lack of appropriate annulus closure techniques is increasingly being recognised as a major limiting factor. In the current study, in vitro and in vivo evaluation of novel annulus closure devices (ACDs) was performed. These devices are intended to be used in adjunct to nucleus replacement therapies in an experimental goat study. After a standardised discectomy had been performed, different ACDs were implanted solely or in addition to a collagen nucleus replacement implant. Biomechanical effects and axial failure load were assessed in vitro and followed by in vivo evaluation in a goat model. On axial compression, the average axial failure load for ACDs with four barb rings was significantly higher compared to the implants with five barb rings. The increased range of flexion-extension and latero-flexion observed after discectomy were restored to the normal range after implantation of the implants. Positive findings with the four-ring ACD were confirmed in goats after a follow-up of 2 weeks in vivo. However, after 6 weeks most implants (n = 16) showed signs of destruction and displacement. Although there seemed to be a tendency towards better results when ACDs were placed in addition to the nucleus replacements, these differences were not statistically significant. Moreover, two endplate reactions extending into the subchondral bone were observed, most likely due to continuous friction between the ACD and the vertebrae. Although current results are encouraging first steps towards the development of an efficient ACD for animal models, further optimisation is necessary. Current results also show that one cannot rely on in vitro biomechanical studies with annulus closure techniques, and these should always be confirmed in vivo in a large animal mode

Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed

Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs

Intervertebral disc (IVD) degeneration involves a series of biochemical and morphological changes leading to loss of spinal stability and flexibility. Cell therapy is promising to reconstitute IVDs with new cells, however, sustained metabolic activity seems crucial for an active contribution to regeneration. The aim of the present study was to establish methods for separate follow up of persistence and activity of autologous porcine mesenchymal stem cells (pMSC) after implantation into IVDs of Goettingen minipigs in vivo in order to conclude about the potential of such an intervention strategy. For quantitative follow up, the transfer matrix was supplemented with Al2O3 particles and pMSC which were retrovirally labeled with firefly luciferase (pMSC-Luc). Six mature Goettingen minipigs underwent matrix based cell transfer after partial nucleotomy of lumbar IVDs (n = 24). Day 0 and day 3 segments were analyzed for retained volume of Al2O3 particles by micro-computed-tomography (μCT) and for cell activity by luciferase enzyme assessment. Three days after injection a reduction of Al2O3 particles (P = 0.028) to about 9% and of pMSC-Luc activity to about 7% of initial values (P = 0.003) was detected, which suggests loss of 90% of the implant material under in vivo conditions without evidence for reduced pMSC-Luc metabolic activity (P = 0.887). In conclusion, separate follow up of implant material and cell activity was possible and unravels problems with in vivo implant persistence after annular puncture rather than quick loss of cell activity. Therefore, IVD-regeneration-strategies should increasingly focus on annulus reconstruction in order to reduce implant loss due to annular failure