Intervertebral disc damage models in organ culture: a comparison of annulus fibrosus cross-incision versus punch model under complex loading

Frauchiger, Daniela Angelika; Chan, Samantha; Benneker, Lorin Michael; Gantenbein, Benjamin

doi:10.1007/s00586-018-5638-5

Cited by 11 publications

(16 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While HG medium is most commonly used for culturing ex vivo disc organ models, 6,9,11,18,36,38,78‐86 the results of this study suggests that HG culturing creates supraphysiological levels in the disc centre (8‐12 mM) when compared to predicted in vivo glucose concentrations of 0.2 to 1.9 mM under degenerative conditions 55‐63 . An important distinction between in vivo and ex vivo nutrition is the pathway of nutrient transport.…”

Section: Discussionmentioning

confidence: 76%

“…21 The popularity of ex vivo disc organ culture has grown over the past decade (Figure 1A) with the focus being either the development of bioreactor systems [22][23][24][25][26][27][28][29] or their utilization to investigate degeneration processes [1][2][3][4][5][6][7][8][9] or regeneration strategies. [10][11][12][13][14][15][16][17][18][19][20] Discs from a variety of different species including mouse, 30,31 rat, 32,33 lapine, 1,34 bovine, [35][36][37][38] ovine, 39,40 caprine, 22,41 porcine 24,42 and human 3,19 have been used. Bovine caudal discs have become a widely accepted model for ex vivo disc organ culture as reflected by their popularity in published works...…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating the physiological relevance of ex vivo disc organ culture nutrient microenvironments using in silico modeling and experimental validation

McDonnell

Buckley

2021

JOR Spine

View full text Add to dashboard Cite

Background: Ex vivo disc organ culture systems have become a valuable tool for the development and pre-clinical testing of potential intervertebral disc (IVD) regeneration strategies. Bovine caudal discs have been widely selected due to their large availability and comparability to human IVDs in terms of size and biochemical composition. However, despite their extensive use, it remains to be elucidated whether their nutrient microenvironment is comparable to human degeneration.Aims: This work aims to create the first experimentally validated in silico model which can be used to predict and characterize the metabolite concentrations within ex vivo culture systems.Materials & Methods: Finite element models of cultured discs governed by previously established coupled reaction-diffusion equations were created using COMSOL Multiphysics. Experimental validation was performed by measuring oxygen, glucose and pH levels within discs cultured for 7 days, in a static compression bioreactor. Results:The in silico model was successfully validated through good agreement between the predicted and experimentally measured concentrations. For an ex vivo organ cultured in high glucose medium (4.5 g/L or 25 mM) and normoxia, a larger bovine caudal disc (Cd1-2 to Cd3-4) had a central concentration of 2.6 %O 2 , 8 mM of glucose and a pH value of 6.7, while the smallest caudal discs investigated (Cd6-7 and Cd7-8), had a central concentration of 6.5 %O 2 , 12 mM of glucose and a pH value of 6.9.Discussion: This work advances the knowledge of ex vivo disc culture microenvironments and highlights a critical need for optimization and standardization of culturing conditions. Conclusion:Ultimately, for assessment of cell-based therapies and successful clinical translation based on nutritional demands, it is imperative that the critical metabolite values within organ cultures (minimum glucose, oxygen and pH values) are physiologically relevant and comparable to the stages of human degeneration.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Investigating the physiological relevance of ex vivo disc organ culture nutrient microenvironments using in silico modeling and experimental validation

McDonnell

Buckley

2021

JOR Spine

View full text Add to dashboard Cite

show abstract

“…For example, collagen fiber diameter and stiffness can be readily modified based on structural and mechanical changes noted with degeneration, or diseases such as diabetes ( Adams and Roughley, 2006 ; Li et al, 2013 ; Svensson et al, 2018 ). Furthermore, the model can be easily modified to evaluate advanced tissue engineering designs (e.g., angle-ply disc replacements) before conducting costly and time-intensive in vivo studies in large animal models ( Martin et al, 2014 ), or to help track time-dependent changes during bioreactor organ cultures ( Frauchiger et al, 2018 ; Pfannkuche et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

A Robust Multiscale and Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc

Zhou

Lim

O’Connell

2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

A comprehensive understanding of multiscale and multiphasic intervertebral disc mechanics is crucial for designing advanced tissue engineered structures aiming to recapitulate native tissue behavior. The bovine caudal disc is a commonly used human disc analog due to its availability, large disc height and area, and similarities in biochemical and mechanical properties to the human disc. Because of challenges in directly measuring subtissue-level mechanics, such as in situ fiber mechanics, finite element models have been widely employed in spinal biomechanics research. However, many previous models use homogenization theory and describe each model element as a homogenized combination of fibers and the extrafibrillar matrix while ignoring the role of water content or osmotic behavior. Thus, these models are limited in their ability in investigating subtissue-level mechanics and stress-bearing mechanisms through fluid pressure. The objective of this study was to develop and validate a structure-based bovine caudal disc model, and to evaluate multiscale and multiphasic intervertebral disc mechanics under different loading conditions and with degeneration. The structure-based model was developed based on native disc structure, where fibers and matrix in the annulus fibrosus were described as distinct materials occupying separate volumes. Model parameters were directly obtained from experimental studies without calibration. Under the multiscale validation framework, the model was validated across the joint-, tissue-, and subtissue-levels. Our model accurately predicted multiscale disc responses for 15 of 16 cases, emphasizing the accuracy of the model, as well as the effectiveness and robustness of the multiscale structure-based modeling-validation framework. The model also demonstrated the rim as a weak link for disc failure, highlighting the importance of keeping the cartilage endplate intact when evaluating disc failure mechanisms in vitro. Importantly, results from this study elucidated important fluid-based load-bearing mechanisms and fiber-matrix interactions that are important for understanding disease progression and regeneration in intervertebral discs. In conclusion, the methods presented in this study can be used in conjunction with experimental work to simultaneously investigate disc joint-, tissue-, and subtissue-level mechanics with degeneration, disease, and injury.

show abstract

“…Of course, there are anatomical differences to be considered to the human IVD and the fact that facet joints and muscle connections had to be omitted [ 24 ]. The biopsy punch injury model has been proposed now by two recent studies [ 34 , 35 ], which resulted in about 50% penetration depth of the IVD diameter [ 35 ]. It is currently unknown how bigger damage models would respond when even >50% or more of the tissue was penetrated and mechanically removed.…”

Section: Discussionmentioning

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

Self Cite

View full text Add to dashboard Cite

(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.

show abstract

Intervertebral disc damage models in organ culture: a comparison of annulus fibrosus cross-incision versus punch model under complex loading

Cited by 11 publications

References 34 publications

Investigating the physiological relevance of ex vivo disc organ culture nutrient microenvironments using in silico modeling and experimental validation

Investigating the physiological relevance of ex vivo disc organ culture nutrient microenvironments using in silico modeling and experimental validation

A Robust Multiscale and Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc

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

Contact Info

Product

Resources

About