Yu-Chun Hsu

A meta-model analysis of a finite element simulation for defining poroelastic properties of intervertebral discs.

Finite element analysis is an effective tool to evaluate the material properties of living tissue. For an interactive optimization procedure, the finite element analysis usually needs many simulations to reach a reasonable solution. The meta-model analysis of finite element simulation can be used to reduce the computation of a structure with complex geometry or a material with composite constitutive equations. The intervertebral disc is a complex, heterogeneous, and hydrated porous structure. A poroelastic finite element model can be used to observe the fluid transferring, pressure deviation, and other properties within the disc. Defining reasonable poroelastic material properties of the anulus fibrosus and nucleus pulposus is critical for the quality of the simulation. We developed a material property updating protocol, which is basically a fitting algorithm consisted of finite element simulations and a quadratic response surface regression. This protocol was used to find the material properties, such as the hydraulic permeability, elastic modulus, and Poisson’s ratio, of intact and degenerated porcine discs. The results showed that the in vitro disc experimental deformations were well fitted with limited finite element simulations and a quadratic response surface regression. The comparison of material properties of intact and degenerated discs showed that the hydraulic permeability significantly decreased but Poisson’s ratio significantly increased for the degenerated discs. This study shows that the developed protocol is efficient and effective in defining material properties of a complex structure such as the intervertebral disc.

Spinal Traction Promotes Molecular Transportation in a Simulated Degenerative Intervertebral Disc Model

Study Design. Biomechanical experiment using an in situ porcine model. Objective. To find the effect of traction treatment on annulus microstructure, molecular convection, and cell viability of degraded discs. Summary of Background Data. Spinal traction is a conservative treatment for disc disorders. The recognized biomechanical benefits include disc height recovery, foramen enlargement, and intradiscal pressure reduction. However, the influence of traction treatment on annulus microstructure, molecular transportation, and cell viability of degraded discs has not been fully investigated. Methods. A total of 48 thoracic discs were dissected from 8 porcine spines (140 kg, 6-month old) within 4 hours after killing them and then divided into 3 groups: intact, degraded without traction, and degraded with traction. Each disc was incubated in a whole-organ culture system and subjected to diurnal loadings for 7 days. Except for the intact group, discs were degraded with 0.5 mL of trypsin on day 1 and a 5-hour fatigue loading on day 2. From day 4 to day 6, half of the degraded discs received a 30-minute traction treatment per day (traction force: 20 kg; loading: unloading = 30 s: 10 s). By the end of the incubation, the discs were inspected for disc height loss, annulus microstructure, molecular (fluorescein sodium) intensity, and cell viability. Results. Collagen fibers were crimped and delaminated, whereas the pores were occluded in the annulus fibrosus of the degraded discs. Molecular transportation and cell viability of the discs decreased after matrix degradation. With traction treatment, straightened collagen fibers increased within the degraded annulus fibrosus, and the annulus pores were less occluded. Both molecular transportation and cell viability increased, but not to the intact level. Conclusion. Traction treatment is effective in enhancing nutrition supply and promoting disc cell proliferation of the degraded discs. Level of Evidence: N/A

Rheological and dynamic integrity of simulated degenerated disc and consequences after cross-linker augmentation.

Study Design. An in situ study using whole-organ culture system. Objective. To study the effect of disc degeneration at different stages on its rheological and dynamic properties and to investigate the efficacy of exogenous cross-linking therapy. Summary of Background Data. Disc degeneration can involve protein denaturation or microdefects to the discs collagen fiber network. A disc degeneration model using whole-organ culture technique can be effectively used for the screening of treatments of degenerated discs. Exogenous cross-linking therapy has been shown to enhance the mechanical properties of the disc by cross-linking collagen. However, the efficacy of this therapy on the degenerated disc is unclear. Methods. A total of 40 porcine thoracic discs were assigned to 5 groups: intact discs, moderately degenerated discs, moderately degenerated discs with cross-linker augmentation, severely degenerated discs, and severely degenerated discs with cross-linker augmentation. The disc degeneration was simulated by trypsin digestion and mechanical fatigue loading. Rheological properties, dynamic properties, water content, and histological analysis were conducted after a 7-day incubation. Results. The mechanical properties of moderate degenerated discs significantly decrease both in rheological and dynamic properties, and laminate structure disorganization was observed. Mechanical defects of severely degenerated discs resulted in disc height loss, an increase in the aggregate modulus and stiffness modulus, and a decrease in the damping coefficient, hydraulic permeability, and water content. Cross-linker augmentation significantly recovered mechanical properties of moderately degenerated discs and restored the water content compared with the intact disc. However, the augmentation did not fully repair the severely degenerated discs. Conclusion. Trypsin-induced extracellular matrix damage resulted in a change of the discs biomechanics. Cross-linker augmentation recovers the rheological and dynamic properties of moderately degenerated discs but not of the severely degenerated discs. The genipin cross-linker may be able to improve the proteoglycan depletion effect in the nucleus pulposus but may not be effective to restore the structural damage in the collagen molecule of the anulus fibrosus. Level of Evidence: N/A

A regenerative approach towards recovering the mechanical properties of degenerated intervertebral discs: Genipin and platelet-rich plasma therapies

Degenerative disc disease, associated with discrete structural changes in the peripheral annulus and vertebral endplate, is one of the most common pathological triggers of acute and chronic low back pain, significantly depreciating an individual’s quality of life and instigating huge socioeconomic costs. Novel emerging therapeutic techniques are hence of great interest to both research and clinical communities alike. Exogenous crosslinking, such as Genipin, and platelet-rich plasma therapies have been recently demonstrated encouraging results for the repair and regeneration of degenerated discs, but there remains a knowledge gap regarding the quantitative degree of effectiveness and particular influence on the mechanical properties of the disc. This study aimed to investigate and quantify the material properties of intact (N = 8), trypsin-denatured (N = 8), Genipin-treated (N = 8), and platelet-rich plasma–treated (N = 8) discs in 32 porcine thoracic motion segments. A poroelastic finite element model was used to describe the mechanical properties during different treatments, while a meta-model analytical approach was used in combination with ex vivo experiments to extract the poroelastic material properties. The results revealed that both Genipin and platelet-rich plasma are able to recover the mechanical properties of denatured discs, thereby affording promising therapeutic modalities. However, platelet-rich plasma–treated discs fared slightly, but not significantly, better than Genipin in terms of recovering the glycosaminoglycans content, an essential building block for healthy discs. In addition to investigating these particular degenerative disc disease therapies, this study provides a systematic methodology for quantifying the detailed poroelastic mechanical properties of intervertebral disc.

Effect of Degeneration on Fluid-Solid Interaction within Intervertebral Disk Under Cyclic Loading - A Meta-Model Analysis of Finite Element Simulations.

The risk of low back pain resulted from cyclic loadings is greater than that resulted from prolonged static postures. Disk degeneration results in degradation of disk solid structures and decrease of water contents, which is caused by activation of matrix digestive enzymes. The mechanical responses resulted from internal solid–fluid interactions of degenerative disks to cyclic loadings are not well studied yet. The fluid–solid interactions in disks can be evaluated by mathematical models, especially the poroelastic finite element (FE) models. We developed a robust disk poroelastic FE model to analyze the effect of degeneration on solid–fluid interactions within disk subjected to cyclic loadings at different loading frequencies. A backward analysis combined with in vitro experiments was used to find the elastic modulus and hydraulic permeability of intact and enzyme-induced degenerated porcine disks. The results showed that the averaged peak-to-peak disk deformations during the in vitro cyclic tests were well fitted with limited FE simulations and a quadratic response surface regression for both disk groups. The results showed that higher loading frequency increased the intradiscal pressure, decreased the total fluid loss, and slightly increased the maximum axial stress within solid matrix. Enzyme-induced degeneration decreased the intradiscal pressure and total fluid loss, and barely changed the maximum axial stress within solid matrix. The increase of intradiscal pressure and total fluid loss with loading frequency was less sensitive after the frequency elevated to 0.1 Hz for the enzyme-induced degenerated disk. Based on this study, it is found that enzyme-induced degeneration decreases energy attenuation capability of disk, but less change the strength of disk.

Recovering the mechanical properties of denatured intervertebral discs through Platelet-Rich Plasma therapy.

Degenerative disc disease is one of the most common causes of low back pain instigating huge socioeconomic costs and posing an immense burden on healthcare systems worldwide. New therapeutic approaches to damaged intervertebral discs are therefore of great interest. Platelet-Rich Plasma (PRP) has been proposed for the repair and regeneration of degenerated discs, but there remains a knowledge gap regarding its effectiveness and influence on disc material properties. The objective of this study was to investigate and quantify the material properties of intact, denatured, and PRP treated discs. A systematic methodology was established in the process, where ex-vivo experiments were conducted and material properties were extracted using an inverse finite element approach. The results showed that PRP is able to recover the mechanical properties of denatured discs, thereby providing a promising effective therapeutic modality.