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Aim:  To explore the effects of viable allogeneic disc tissue supplementation in younger patients with discogenic chronic low back pain (CLBP). Patients & methods: VAST was a randomized placebo-controlled trial of disc allograft supplementation in 218 patients with discogenic CLBP. We conducted a post hoc analysis of change from baseline to 12 months in Oswestry Disability Index (ODI) and visual analog scale for pain intensity scores stratified by patient age. Results: Patients aged <42 years receiving allograft experienced greater improvement in ODI (p = 0.042) and a higher ODI response rate (≥10-, ≥15- and ≥20-point reductions in ODI) than those receiving saline (p = 0.001, p = 0.002 and p = 0.021, respectively). Conclusion: Young patients with discogenic CLBP may have significant functional improvement following nonsurgical disc allograft supplementation.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 10 6 or 2 × 10 6 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

In the last decade, intervertebral disc (IVD) decellularization has gained significant attention for tissue regenerative purposes as a successful therapeutic alternative for low back pain (LBP). We discuss the recent advances in IVD decellularization, repopulation, and sterilization procedures, highlighting the major challenges that need to be addressed for clinical translation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A biomaterial-based strategy is employed to regenerate the degenerated intervertebral disc, which is considered a major generator of neck and back pain. Although encouraging enhancements in the anatomy and kinematics of the degenerative disc have been gained by biomaterials with various formulations in animals, the number of biomaterials tested in humans is rare. At present, most studies that involve the use of newly developed biomaterials focus on regeneration of the degenerative disc, but not pain relief. In this review, we summarise the current state of the art in the field of biomaterial-based regeneration or repair for the nucleus pulposus, annulus fibrosus, and total disc transplantation in animals and humans, and we then provide essential suggestions for the development and clinical translation of biomaterials for disc regeneration. It is important for researchers to consider the commonly neglected issues instead of concentrating solely on biomaterial development and fabrication., (© 2018 John Wiley & Sons, Ltd.)

Objective: To discuss the effect of three different ways of annulus fibrosus incision on the biomechanical strength of intervertebral disc., Methods: A total of 30 goats underwent intervertebral disc nucleus pulposus extraction at L3,4 and 45 by the working channel in group A (n=10), by circular incision in group B (n=10), and by square incision in group C (n=10). The body weight, male and female ratio, age, intraoperative blood loss, and wound healing time were recorded and compared among 3 groups. The survival rate and wound healing situation were observed after operation. At 24 weeks after operation, the goats were sacrificed, MRI images were taken to observe the signal intensity of nucleus pulposus. The disc height of L(3,4) and L(4,5) was measured to calculate the loss of disc height; biomechanical test was used to assess the strength of the disc and anulus. Histological staining was also conducted to observe the repair effect at L(4,5)., Results: There was no significant difference in body weight, male to female ratio, age, intraoperative blood loss, and wound healing time among groups (P>0.05). All goats survived to the end of the experiment. MRI examination showed decreased signal intensity in 3 groups, indicating intervertebral disc degeneration. According to modified Thompson classification method, the degree of intervertebral disc degeneration of group A was significantly higher than that of groups B and C (P<0.05), but no significant difference was found between groups B and C (P>0.05). Difference was not significant in intervertebral space height before operation among 3 groups (P>0.05). But after 24 weeks, the intervertebral space height in group A was significantly higher than that in groups B and C (P<0.05), and the intervertebral space height loss in group A was significantly lower than that in groups B and C (P<0.05). The biomechanical strength in group A was also significantly higher than that in groups B and C (P<0.05), but no significant difference was found between group B and group C (P>0.05). HE and Masson staining showed good continuity of annulus fibrosus and clear layers in group A; poor continuity of annulus fibrosus and obvious scar tissues were observed in groups B and C., Conclusion: Application of working channel may have less destruction of annulus fibrosus, it plays a positive role in the maintenance of biomechanical strength and repair of annulus fibrosus.

Purpose: Fresh-frozen intervertebral disc transplantation was determined to be an effective treatment for degenerative disc diseases in rhesus monkeys and in humans. Further research in improving different aspects of disc allografts transplantation is needed and will be investigated in large animal models. This study reports the detailed surgical technique of intervertebral disc transplantation without internal fixation and the important notes to ensure success in goats., Methods: Fifty-one male goats were used in this study. Ten goats were used as intervertebral disc allograft donors; the remaining forty-one goats were used to develop the surgical technique for intervertebral disc allograft transplantation. Radiographs, ex vivo MRI and gross observation were used to monitor the stability and healing of the disc allografts at 3 months, postoperatively., Results: Size matching of the disc allograft, preservation of the anterior longitudinal ligament and an appropriate portion of the annulus fibrosus at the recipient site were crucial for stable graft retention. Additionally, a slightly reduced height of the disc allograft compared to that of the recipient slot may avoid graft endplate fracture., Conclusions: Lumbar intervertebral disc transplantation without internal fixation can be successfully performed in goats.

Object: Tissue-engineered intervertebral discs (TE-IVDs) represent a new experimental approach for the treatment of degenerative disc disease. Compared with mechanical implants, TE-IVDs may better mimic the properties of native discs. The authors conducted a study to evaluate the outcome of TE-IVDs implanted into the rat-tail spine using radiological parameters and histology., Methods: Tissue-engineered intervertebral discs consist of a distinct nucleus pulposus (NP) and anulus fibrosus (AF) that are engineered in vitro from sheep IVD chondrocytes. In 10 athymic rats a discectomy in the caudal spine was performed. The discs were replaced with TE-IVDs. Animals were kept alive for 8 months and were killed for histological evaluation. At 1, 5, and 8 months, MR images were obtained; T1-weighted sequences were used for disc height measurements, and T2-weighted sequences were used for morphological analysis. Quantitative T2 relaxation time analysis was used to assess the water content and T1ρ-relaxation time to assess the proteoglycan content of TE-IVDs., Results: Disc height of the transplanted segments remained constant between 68% and 74% of healthy discs. Examination of TE-IVDs on MR images revealed morphology similar to that of native discs. T2-relaxation time did not differ between implanted and healthy discs, indicating similar water content of the NP tissue. The size of the NP decreased in TE-IVDs. Proteoglycan content in the NP was lower than it was in control discs. Ossification of the implanted segment was not observed. Histological examination revealed an AF consisting of an organized parallel-aligned fiber structure. The NP matrix appeared amorphous and contained cells that resembled chondrocytes., Conclusions: The TE-IVDs remained viable over 8 months in vivo and maintained a structure similar to that of native discs. Tissue-engineered intervertebral discs should be explored further as an option for the potential treatment of degenerative disc disease.

Objectives: To investigate whether the intervention of nucleus pulposus (NP) cells or human telomerase reverse transcriptase (hTERT) gene-transfected NP cells can prevent the degeneration process after allograft total disc transplantation., Methods: Eighteen canine lumbar intervertebral discs were obtained from five canines and cryopreserved in liquid nitrogen. Canine nucleus pulposus cells were isolated and transduced with recombinant adeno-associated virus (rAAV)-hTERT. The cells were injected into the discs to construct a tissue-engineered allograft disc (group A). NP cells and DMEM/F12 were used for positive control (group B) and blank control (group C). 18 beagle dogs received the three groups of allograft intervertebral disc (IVD) composites implantation, respectively. Radiographic examinations were performed at 4, 8, and 12 weeks postimplantation. At 12 weeks after operation, all dogs were sacrificed and the lumbar spines were harvested for the biomechanical analysis, and then the allografts underwent histological analysis, ectogenic NP cell tracing, and hTERT mRNA analysis., Results: Bony fusion between the intervertebral disc allograft and the adjacent host intervertebral body were observed in all animals. The disc height and T2 signal intensity preservation in group A and B was better than group C. Magnetic resonance images (MRI) showed typical degenerative changes in group C. In group A, the normalized grayscale of the transplanted disc on MRI was significant higher compared with the controls at 12 weeks. A biomechanical test showed a poor stability preservation in group C compared to group A and B. PKH-26-positive cells were identified within the allograft discs in group A at 12 weeks, providing evidence of cell survival. Histological analysis showed the NP cell morphology, cell number, and distribution of the allograft discs was better preserved in group A and B compared to group C at a 12-week follow-up., Conclusion: The present study demonstrated that NP cells or hTERT-loaded NP cells intervention could effectively resist the degeneration of the allogenic transplanted intervertebral discs in a beagle model. The hTERT-loaded NP cells had a better antidegeneration effect on the transplanted disc than NP cells. This modified disc regeneration technique through NP cell injection or manipulation may have the potential to ensure the long-term function preservation of allograft disc transplantation.