Simulation of biological therapies for degenerated intervertebral discs

Abstract

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.

Keywords: biomechanics; disc repair; finite element model.

Figure 1

(A) A picture of a human lumbar disc (L2-3, male, non-degenerated). (B) The upper-right quarter of the disc for simulation. (C) GAG content and (D) water content distributions in the mildly degenerated disc before treatment. (E) GAG content and (F) water content distributions in the severely degenerated disc before treatment. All the values are normalized to that at the healthy state.

Figure 2

Comparisons of GAG content (normalized to that at the healthy state) in the severely degenerated disc treated with various cell densities in Case I: (A) 4000 cells/mm³, (B) 8000 cells/mm³, and (C) 12000 cells/mm³. The treatment is under normal nutrition level at the disc boundary.

Figure 3

Comparisons of water content (normalized to that at the healthy state) in the severely degenerated disc treated with various cell densities in Case I: (A) 4000 cells/mm³, (B) 8000 cells/mm³, and (C) 12000 cells/mm³. The treatment is under normal nutrition level at the disc boundary.

Figure 4

Comparisons of treatment outcomes in the severely degenerated disc treated with various cell densities in Case I: (A) GAG content, (B) water content, and (C) disc height. The treatment is under normal nutrition level at the disc boundary. Values in (A) and (B) are averaged over NP.

Figure 5

Comparisons of treatment outcomes in the severely degenerated disc treated with a cell density of 8000 cells/mm³ in Case I between normal nutrition level and lower nutrition level (e.g., 1.6 mM for glucose, and 1.8 kPa for oxygen on the NP surface, while normal level remains on AF periphery): (A-B) GAG content, (C-D) water content.

Figure 6

The critical nutrition level (minimum level of glucose at the NP surface for cell survival) versus the cell density in the NP in severely degenerated disc treated with various cell densities in Case I.

Figure 7

Comparison of treatment outcomes between mildly and severely degenerated discs and between non-treated (control) and treated discs in Case II (i.e., increasing GAG synthesis rate in the NP): spatial distributions of GAG content (A, C) and water content (B, D), and temporal variations of GAG content (E), water content (F), and disc height (G). The treatment is under normal nutrition level at the disc boundary. All the values are normalized to that at the healthy state. Values in (E) and (F) are averaged over NP.

Figure 8

Comparison of treatment outcomes between mildly and severely degenerated discs and between non-treated (control) and treaded discs in Case III (decreasing GAG degradation rate in the NP): spatial distributions of GAG content (A-D) and water content (E-H) after 5 year, and temporal variations of GAG content (I), water content (J), and disc height (K). The treatment is under normal nutrition level at the disc boundary. All the values are normalized to that at the healthy state. Values in (I) and (J) are averaged over NP.