The purpose of this review was to compare the efficacy and safety of synthetic bone graft substitutes versus autograft or allograft for the treatment of lumbar and cervical spinal degenerative ...diseases. Multiple major medical reference databases were searched for studies that evaluated spinal fusion using synthetic bone graft substitutes (either alone or with an autograft or allograft) compared with autograft and allograft. Randomized controlled trials (RCT) and cohort studies with more than 10 patients were included. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. The search yielded 214 citations with 27 studies that met the inclusion criteria. For the patients with lumbar spinal degenerative disease, data from 19 comparative studies were included: 3 RCTs, 12 prospective, and 4 retrospective studies. Hydroxyapatite (HA), HA+collagen, β-tricalcium phosphate (β-TCP), calcium sulfate, or polymethylmethacrylate (PMMA) were used. Overall, there were no differences between the treatment groups in terms of fusion, functional outcomes, or complications, except in 1 study that found higher rates of HA graft absorption. For the patients with cervical degenerative conditions, data from 8 comparative studies were included: 4 RCTs and 4 cohort studies (1 prospective and 3 retrospective studies). Synthetic grafts included HA, β-TCP/HA, PMMA, and biocompatible osteoconductive polymer (BOP). The PMMA and BOP grafts led to lower fusion rates, and PMMA, HA, and BOP had greater risks of graft fragmentation, settling, and instrumentation problems compared with iliac crest bone graft. The overall quality of evidence evaluating the potential use and superiority of the synthetic biological materials for lumbar and cervical fusion in this systematic review was low or insufficient, largely due to the high potential for bias and small sample sizes. Thus, definitive conclusions or recommendations regarding the use of these synthetic materials should be made cautiously and within the context of the limitations of the evidence.
Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant's ...therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant's influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.
Therapeutic treatment of intervertebral disc repair using cells.
The goal of the study was to test the hypothesis that repair of a damaged disc is possible using autologous adipose tissue derived ...stem and regenerative cells (ADRCs).
Degradation resulting from either acute or chronic repetitive disc injury leads to disc degeneration. However, if a damaged disc could be repaired in the early stages, before the onslaught of degradation, then the disc degeneration process may be slowed down.
Twelve dogs underwent a partial nucleotomy at 3 lumbar levels (L3-L4, L4-L5, and L5-L6); adjacent levels served as nonoperated controls. The animals (or discs) were allowed to recover from the surgery for 6 weeks. At that time subcutaneous adipose tissue was harvested and ADRCs were isolated. The 3 experimental discs that had undergone a partial nucleotomy were randomized to receive: (1) ADRCs in hyaluronic acid carrier (Cells/HA); (2) HA only; or (3) No Intervention. Assessments of the 3 experimental discs plus the 2 adjacent untouched discs were made using MRI, radiography, histology, and biochemistry. The animals were killed at 6 months and at 12 months.
Repair in this study was specifically demonstrated through histology and biochemical analysis. Disc levels receiving ADRCs more closely resembled the healthy controls as evidenced in matrix translucency, compartmentalization of the anulus, and in cell density within the nucleus pulposus. Matrix analysis for Type-II collagen and aggrecan demonstrated evidence of a statistically better regenerative stimulation to the disc provided by ADRCs when compared to either the HA only or no intervention treatments.
Autologous adipose tissue derived stem and regenerative cells, as used in this disc injury model, were effective in promoting disc regeneration, as evidenced by disc matrix production and overall disc morphology.
Adjacent segment disease (ASD) is a potential complication following lumbar spinal fusion.
This study aimed to demonstrate the demographic, clinical, and operative risk factors associated with ASD ...development following lumbar fusion.
Systematic review and meta-analysis.
We identified 35 studies that reported risk factors for ASD, with a total number of 7,374 patients who had lumbar spine fusion.
We investigated the demographic, clinical, and operative risk factors for ASD after lumbar fusion.
A literature search was done using PubMed, Embase, Medline, Scopus, and the Cochrane library databases from inception to December 2019. The methodological index for non‐randomized studies (MINORS) criteria was used to assess the methodological quality of the included studies. A meta-analysis was done to calculate the odds ratio (OR) with the 95% confidence interval (CI) for dichotomous data and mean difference (MD) with 95% CI for continuous data.
Thirty-five studies were included in the qualitative analysis, and 22 studies were included in the meta-analyses. The mean quality score based on the MINORS criteria was 12.4±1.9 (range, 8–16) points. Significant risk factors included higher preoperative body mass index (BMI) (mean difference MD=1.97 kg/m2; 95% confidence interval CI=1.49–2.45; p<.001), floating fusion (Odds ratio OR=1.78; 95% CI=1.32–2.41; p<.001), superior facet joint violation (OR=10.43; 95% CI=6.4–17.01; p<.001), and decompression outside fusion construct (OR=1.72; 95% CI=1.25–2.37; p<.001).
The overall level of evidence was low to very low. Higher preoperative BMI, floating fusion, superior facet joint violation, and decompression outside fusion construct are significant risk factors of development of ASD following lumbar fusion surgeries.
Cervical fusion for degenerative disorders carries a known risk of adjacent segment disease (ASD), a complication that often requires surgical intervention to relieve symptoms. Proposed risk factors ...for development of ASD include both clinical and radiographic patient characteristics. However, the true impact of these risk factors is less understood due to limitations in sample sizes and loss to follow-up in individual studies.
To review and critically examine current literature on the clinical risk factors associated with development of ASD in the cervical spine following ACDF.
Systematic Review and Meta-Analysis.
We systematically reviewed the literature in December 2019 according to the PRISMA guidelines. Methodological quality of included papers and quality of evidence were evaluated according to MINORS and GRADE framework. Meta-analysis was performed to compute the odds ratio(OR)with corresponding 95% confidence interval(CI)for dichotomous data, and mean difference(MD) with 95% CI for continuous variables.
6,850 records were obtained using database query. Title/abstract screening resulted in 19 articles for full review, from which 10 papers met the criteria for analysis. There were no significant differences in gender (OR 0.99, 95% CI 0.75–1.30), BMI (MD -0.09, 95% CI -0.46 to 0.29), smoking (OR 1.13, 95% CI 0.80–1.59), alcohol (OR 1.07, 95% CI 0.70–1.64), diabetes (OR 0.85, 95% CI 0.56–1.31), number of segments fused (OR 0.86, 95% CI 0.64–1.16), and preoperative JOA (MD -0.50, 95% CI -1.04 to 0.04). Age (MD 3.21, 95% CI 2.00–4.42), congenital/developmental stenosis (OR 1.94, 95% CI 1.06–3.56), preoperative NDI (MD 4.18, 95% CI 2.11 to 6.26), preoperative VAS (neck) (MD 0.54 95% CI 0.09–0.99), and preoperative VAS (arm) (MD 0.98, 95% CI 0.43–1.34) were found to be statistically significant risk factors.
Patients with congenital stenosis, advanced age, and high preoperative NDI are at increased risk of developing ASD.
Study Design:
Systematic review.
Objective:
To review, critically appraise, and synthesize evidence on use of cell therapy for intervertebral disc repair.
Methods:
A systematic search of ...PubMed/MEDLINE was conducted for literature published through October 31, 2018 and EMBASE and ClinicalTrials.gov databases through April 13, 2018 comparing allogenic or autologous cell therapy for intervertebral disc (IVD) repair in the lumbar or cervical spine. In the absence of comparative studies, case series of ≥10 patients were considered.
Results:
From 1039 potentially relevant citations, 8 studies across 10 publications on IVD cell therapies in the lumbar spine met the inclusion criteria. All studies were small and primarily case series. For allogenic cell sources, no difference in function or pain between mesenchymal cell treatment and sham were reported in 1 small randomized controlled trial; 1 small case series reported improved function and pain relative to baseline but it was unclear if the change was clinically significant. Similarly for autologous cell sources, limited data across case series suggest pain and function may be improved relative to baseline; whether the changes were clinically significant was not clear. Safety data was sparse and poorly reported. The need for subsequent surgery was reported in 3 case-series studies ranging from 6% to 80%.
Conclusions:
The overall strength of evidence for efficacy and safety of cell therapy for lumbar IVD repair was very low primarily due to substantial risk of bias, small sample sizes and lack of a comparator intervention. Methodologically sound studies comparing cell therapies to other treatments are needed.
Background: In the regeneration and therapy of degenerated intervertebral discs, the height, volume or categorizing assessments, such as Pfirrmann classification, are used to quantify the discs ...themselves and the effects of therapy. Here, the question of transferability, in the sense of reliability, of the results arises in the common exchange. Methods: We have investigated two established and a newly developed (9-point measurement), easy to use methods for height measurement and volume measurement on degenerated and healthy lumbar intervertebral discs of 66 patients regarding inter- and intra-observer reliability. Results: In overview, we found very different reliabilities. While the intra-observer reliability showed good to excellent agreement for both healthy and degenerated lumbar discs for the height and volume measurements, the inter-observer reliability was low or moderate in some cases. The 9-point method for height determination consistently showed better reliability for both healthy and degenerated discs, for both intra- and inter-observer reliability, compared to the two established methods. Conclusions: We recommend using the 9-point measurement as the method to communicate lumbar disc height, both for healthy and degenerated discs. Due to the partly low or moderate reliability, significant differences in the measured heights can already occur, which can lead to a worsened comparability.
Disc degeneration and osteoarthritis are diseases of the matrix. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce, and secrete matrix ...components, and respond to physical stimuli such as dynamic loading. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc.
Given the capacity for the cells in vitro to produce matrix molecules that would be appropriate for disc chondrocytes, the focus of the experiment was to investigate whether the cells would continue to sustain metabolic function after transplantation.
No evidence for long-term integration exists for cell transplantation in species other than rats and rabbits. Furthermore, no controlled studies of 1-year duration have been published.
Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair.
In the context of degenerative changes in an injury model: (1) autologous disc chondrocytes were expanded in culture and returned to the disc by a minimally invasive procedure after 12 weeks; (2) disc chondrocytes remained viable after transplantation as shown by Bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; (3) transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; (4) both type II and type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and (5) when the disc heights were analyzed for variance according to treatment, a statistically significantcorrelation between transplanting cells and retention of disc height was achieved.
Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.
Study design:
Systematic review.
Objectives:
To systematically review, critically appraise and synthesize evidence on use of autologous stem cells sources for fusion in the lumbar spine.
Methods:
A ...systematic search of PubMed/MEDLINE, EMBASE and ClinicalTrials.gov through February 20, 2020 was conducted comparing autologous cell grafts to other biologics for lumbar spine fusion. The focus was on studies comparing distinct patient groups.
Results:
From 343 potentially relevant citations, 15 studies met the inclusion criteria set a priori. Seven studies compared distinct patient groups, with BMA being used in combination with allograft or autograft not as a standalone material. No economic evaluations were identified. Most observational studies were at moderately high risk of bias. When used for primary lumbar fusion, no statistical differences in outcomes or complications were seen between BMA+autograft/or +allograft compared to autograft/allograft alone. Compared with allograft, data from a RCT suggested statistically better fusion and lower complication rates with concentrated BMA+allograft. When used in revisions, no differences in outcomes were seen between BMA+allograft and either autograft or rh-BMP-2 but fusion rates were lower with BMA+allograft, leading to additional revision surgery.
Conclusions:
There was substantial heterogeneity across studies in patient populations, sample size, biologic combinations, and surgical characteristics making direct comparisons difficult. The overall quality of evidence for fusion rates and the safety of BMA in lumbar fusion procedures was considered very low, with studies being at moderately high or high risk of bias.
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