29 research outputs found
Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical
Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is frought with many hurdles to overcome. Many of the keys to success are not necessarily linked to science or innovation. Successful translation to clinic will also rely on planning and awareness of the hurdles. It will be essential to plan your entire path to clinic from the outset and to do this with a multidisciplinary team. Take advise early on regulatory aspects and focus on generating the proof required to satisfy regulatory approval. Scientific demonstration and societal benefits are important, but translation cannot occur without involving commercial parties, which are instrumental to support expensive clinical trials. This will only be possible when intellectual property can be protected sufficiently to support a business model. In this manner, commercial, societal, medical, and scientific partners can work together to ultimately improve patient health. Based on literature surveys and experiences of the co‐authors, this opinion paper presents this pathway, highlights the most prominent issues and hopefully will aid in your own transational endeavors
Analysis of Nonlinear Coupled Diffusion of Oxygen and Lactic Acid in Intervertebral Discs
Correlations between effective permeability and marrow contact channels surface of vertebral endplates
Simulation of water content distributions in degenerated human intervertebral discs
The objective of this study was to investigate the spatial and temporal variations of water content in intervertebral discs during degeneration and repair processes. We hypothesized that the patterns of water content distribution in the discs are related to the intensity patterns observed in T2-weighted MRI images. Water content distributions in the mildly (e.g., 80% viable cells in the disc, 2.3% decrease in disc height) and moderately (e.g., 40% viable cells in the disc, 9.3% decrease in disc height) degenerated discs were predicted using a finite element model. The variation of water content in the degenerated discs treated with three biological therapies [i.e., increasing the cell density in the NP (Case I), increasing glycosaminoglycan synthesis rate in the nucleus pulposus (Case II), and decreasing glycosaminoglycan degradation rate in the nucleus pulposus (Case III)] were also predicted. It was found that two patterns of water content distributions, a horizontal region with lower water content at the mid-axial plane of nucleus pulposus and a spot with higher water content at the posterior region, were shown during the degeneration progress for the disc simulated in this study. These two patterns disappeared after treatment in Case I, but in Case II and Case III. The implication of these patterns for the horizontal gray band and high intensity zone in T2-weighted MRI images was discussed. This study provided new guidance to develop a novel method for diagnosing disc degeneration and assessing outcomes of biological therapies with MRI techniques
Influences of Nutrition Supply and Pathways on the Degenerative Patterns in Human Intervertebral Disc
STUDY DESIGN: Investigation of the effects of the impairment of different nutritional pathways on the intervertebral disc degeneration patterns in terms of spatial distributions of cell density, glycosaminoglycan content, and water content. OBJECTIVE: To test the hypothesis that impairment of different nutritional pathways would result in different degenerative patterns in human discs. SUMMARY OF BACKGROUND DATA: Impairment of nutritional pathways has been found to affect cell viability in the disc. However, details on how impairment of different nutritional pathways affects the disc degeneration patterns are unknown. METHODS: A 3D finite element model was used for this study. This finite element method was based on the cell-activity-coupled mechano-electrochemical theory for cartilaginous tissues. Impairment of the nutritional pathways was simulated by lowering the nutrition level at the disc boundaries. Effects of the impartment of cartilaginous endplate-nucleus pulposus (CEP-NP) pathway only (Case 1), annulus fibrosus (AF) pathway only (Case 2), and both pathways (Case 3) on disc degeneration patterns were studied. RESULTS: The predicted critical level of nutrition for Case 1, Case 2, and Case 3 were around 30%, 20%, and 50% of the reference values, respectively. Below this critical level, the disc degeneration would occur. Disc degeneration appeared mainly in the NP for Case 1, in the outer AF for Case 2, and in both the NP and inner to middle AF for Case 3. For Cases 1 and 3, the loss of water content was primarily located in the mid-axial plane, which is consistent with the horizontal gray band seen in some T2-weighted MRI images. For the disc geometry used in this study, it was predicted that there existed a High Intensity Zone (for Case 3), as seen in some T2-weighted MRI images. CONCLUSION: Impairment of different nutrition pathways results in different degenerative patterns
Comparison of Oxygen Consumption Rates of Nondegenerate and Degenerate Human Intervertebral Disc Cells
Acidic pH promotes nucleus pulposus cell senescence through activating the p38 MAPK pathway
Simulation of biological therapies for degenerated intervertebral discs
The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs