Design of a Mechanical Loading Device to Culture Intact Bovine Spinal Motion Segments under Multiaxial Motion

Walser, Jochen; Ferguson, Stephen J.; Gantenbein, Benjamin

doi:10.1002/9781119940685.ch9

Cited by 5 publications

(5 citation statements)

References 64 publications

(60 reference statements)

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“…Considering uni-axial compression, it becomes obvious that disc surface area is relevant and thus determines the force range of the bioreactor force cell and the dimensions of the culture chambers. Disc height and creep determines the required range of displacement [33,41]. Figure 1 depicts a general design of a bioreactor for IVD culture and summarizes current research foci for the establishment of in vitro degeneration and regeneration models.…”

Section: Overview Of Bioreactor Systemsmentioning

confidence: 99%

“…rabbit), a cost-effective alternative is a multi-station loading system, which is integrated into a standard materials testing machine [47], providing the advantage of high throughput for simultaneous stimulation of multiple samples. In terms of loading, most bioreactors focus on uniaxial compressive loading except one that can also investigate torsion as a 2 nd degree of freedom (DoF) by using rough-surface titanium plates to enable torsion [41]. More complex loadings by increasing the DoF up to six have been recently undertaken with formalin fixed samples [48] and studies are under way to use also unfixed live tissue (Costi, personal communication).…”

Section: Overview Of Bioreactor Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

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In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

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Section: Overview Of Bioreactor Systemsmentioning

confidence: 99%

Section: Overview Of Bioreactor Systemsmentioning

confidence: 99%

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

Self Cite

View full text Add to dashboard Cite

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“…For human samples, two bioreactors for compressional loading of lumbar IVDs were designed lately [ 22 , 24 ]. Nevertheless, only one can apply torsion in addition to compression to mimic physiological loading over a prolonged time on living IVDs [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…The three experimental groups were subjected to either no loading, static loading or complex loading conditions [ 12 ]. To mimic physiological loads, complex loading was performed in a two-degree-of-freedom bioreactor that allows for compression and torsion [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Genipin-Enhanced Fibrin Hydrogel and Novel Silk for Intervertebral Disc Repair in a Loaded Bovine Organ Culture Model

Frauchiger

May

Bakırcı

et al. 2018

JFB

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(1) Background: Intervertebral disc (IVD) repair represents a major challenge. Using functionalised biomaterials such as silk combined with enforced hydrogels might be a promising approach for disc repair. We aimed to test an IVD repair approach by combining a genipin-enhanced fibrin hydrogel with an engineered silk scaffold under complex load, after inducing an injury in a bovine whole organ IVD culture; (2) Methods: Bovine coccygeal IVDs were isolated from ~1-year-old animals within four hours post-mortem. Then, an injury in the annulus fibrosus was induced by a 2 mm biopsy punch. The repair approach consisted of genipin-enhanced fibrin hydrogel that was used to fill up the cavity. To seal the injury, a Good Manufacturing Practise (GMP)-compliant engineered silk fleece-membrane composite was applied and secured by the cross-linked hydrogel. Then, IVDs were exposed to one of three loading conditions: no load, static load and complex load in a two-degree-of-freedom bioreactor for 14 days. Followed by assessing DNA and matrix content, qPCR and histology, the injured discs were compared to an uninjured control IVD that underwent the same loading profiles. In addition, the genipin-enhanced fibrin hydrogel was further investigated with respect to cytotoxicity on human stem cells, annulus fibrosus, and nucleus pulposus cells; (3) Results: The repair was successful as no herniation could be detected for any of the three loading conditions. Disc height was not recovered by the repair DNA and matrix contents were comparable to a healthy, untreated control disc. Genipin resulted being cytotoxic in the in vitro test but did not show adverse effects when used for the organ culture model; (4) Conclusions: The current study indicated that the combination of the two biomaterials, i.e., genipin-enhanced fibrin hydrogel and an engineered silk scaffold, was a promising approach for IVD repair. Furthermore, genipin-enhanced fibrin hydrogel was not suitable for cell cultures; however, it was highly applicable as a filler material.

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“…As previous studies show that cell may react differently due to different loading types, cellular stress response in response to static and dynamic loading was studied. Bovine caudal discs were loaded on to a custom made bioreactor [ 32 ] to apply compressive loading. IVD mechanobiology studies were previously performed on this bioreactor, which can maintain cell viability and nutrients diffusion throughout the experiment with dynamic compressive loads applied [ 30 ] ( Fig 1 ).…”

Section: Methodsmentioning

confidence: 99%

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

et al. 2016

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Mechanical loading has been shown to affect cell viability and matrix maintenance in the intervertebral disc (IVD) but there is no investigation on how cells survive mechanical stress and whether the IVD cells perceive mechanical loading as stress and respond by expression of heat shock proteins. This study investigates the stress response in the IVD in response to compressive loading. Bovine caudal disc organ culture was used to study the effect of physiological range static loading and dynamic loading. Cell activity, gene expression and immunofluorescence staining were used to analyze the cell response. Cell activity and cytoskeleton of the cells did not change significantly after loading. In gene expression analysis, significant up-regulation of heat shock protein-70 (HSP70) was observed in nucleus pulposus after two hours of loading. However, the expression of the matrix remodeling genes did not change significantly after loading. Similarly, expressions of stress response and matrix remodeling genes changed with application and removal of the dynamic loading. The results suggest that stress response was induced by physiological range loading without significantly changing cell activity and upregulating matrix remodeling. This study provides direct evidence on loading induced stress response in IVD cells and contributes to our understanding in the mechanoregulation of intervertebral disc cells.

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Design of a Mechanical Loading Device to Culture Intact Bovine Spinal Motion Segments under Multiaxial Motion

Cited by 5 publications

References 64 publications

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Genipin-Enhanced Fibrin Hydrogel and Novel Silk for Intervertebral Disc Repair in a Loaded Bovine Organ Culture Model

Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc Organ Culture

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