Feasibility Analysis of Crosslinker, Platelet-rich Plasma and Traction Treatment on the Recovery of Biomechanical Functions in Simulated Degenerative Intervertebral Disc
Date Issued
2014
Date
2014
Author(s)
Hsu, Yu-Chun
Abstract
Disc degeneration is one of the most common causes of low back pain and the development of appropriate treatment strategies to prevent or slow the degeneration process has gained enormous interest. It has been shown recently that the disc degeneration process may be initiated from inflammatory factors and the associated enzyme activation leading to a chain of reaction including the destruction of anular structural integrity, a change of disc biochemical compositions and significant reduction of water content. Subsequently, maintaining the integrity of extracellular matrix and cell viability by the injection of natural cross-linker and platelet-rich plasma (PRP) has been shown to be a treatment strategy with some great potential. Natural cross-linker has been proven to enhance the resistant strength of intervertebral disc; however, exact effects on disc biochemical properties remain unknown. Furthermore, although PRP is rich in growth factors and have been shown to stimulate the cell proliferation and matrix synthesis process, its ability to return the disc back to pre-injury status is yet to be investigated. Moreover, traction therapy is a physical therapy technique that is commonly prescribed for the treatment of low back pain. Biomechanically, traction is able to increase the foramen space and thus easing the symptoms of back pain, however, the long-term outcome and the associated mechanisms in the prevention of disc degeneration remain unclear.
The first part of this dissertation was to develop an appropriate disc degeneration model based on the injection of trypsin in a whole organ culture system, and to evaluate the treatment efficacy of natural cross-linker (genipin) on microstructure and biomechanical properties of degenerated disc. The results showed that the moderately degenerated disc and severely degenerated disc were successfully simulated by trypsin injection and high magnitude fatigue loading (Frms: 420N, Frequency: 2.5, Loading period: 4 Hours). The rheological, dynamic properties and water content significantly decreased and anular structure was loosen in moderately degenerated discs. In severely degenerated disc, the aggregate modulus and stiffness increased, while the reduction of water content in nucleus pulposus and broken anular structures were observed. Cross-linker therapy restored the rheological and dynamic properties of moderately degenerated disc. It also recovered the water content in nucleus pulposus, however, the hydraulic permeability and damping coefficient significantly decreased due to the unrecoverable anulus structure defects.
In the second part of the dissertation, the recovery efficacy of natural cross-linker and PRP therapy on trypsin-treated degenerated discs were determined by studying the change of disc water content, glycosaminoglycan content and disc biomechanics. The results showed that natural cross-linker has the capacity to recover the aggregate modulus, stiffness and water content in nucleus pulposus. The PRP therapy restored not only the disc biomechanics such as aggregate modulus, hydraulic permeability, stiffness, damping coefficient, but also recovered the disc water content and glycosaminoglycan content. However, both treatments failed to fully recover the disc functions back to its intact level. Overall, the PRP were found to have better treatment efficacy on the recovery of disc biomechanics and biology functions.
In the third part of the dissertation, the efficacy of the traction therapy on microstructure, molecular convection and cell viability of degenerated disc was determined. The results found that post-traction, the anular collagen fibers were delaminated and irregular. The pores in collagen fibrils were occluded which is likely to lower nutrient transportation and decrease cell viability. Traction therapy was found to straighten the collagen fibers and subsequently the annulus pores were found to be less occulded. Overall, the molecular convection and cell viability improved but not to the intact level.
In conclusion, the dissertation provided evidence that the enzymatic digestion on intervertebral disc has the capacity to alter disc biomechanics and biology to successfully simulate disc degeneration with the most profound effect being the occultation of the pores in anular fibrous. The natural cross-linker, PRP therapy, and traction therapy were all effective in the recovery of disc biomechanics and biology; however, all failed to return the degenerated disc back to pre-injury levels. Therefore, future studies should develop treatment strategies to enhance the recovery of degenerated disc that is applicable clinical practice.
Subjects
全椎間盤培養系統
椎間盤退化模型
天然交聯劑
牽引治療
富含血小板之血漿
動態性質
流變學性質
水含量
醣胺聚醣含量
SDGs
Type
thesis
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