A multi-throughput mechanical loading system for mouse intervertebral disc

Xing, Yuan; Zhang, Pu; Zhang, Yangpu; Holzer, Liam; Xiao, Li; He, Yi; Majumdar, Rahul; Jianzhong, Huo; Ramasubramanian, Melur K.; Jin, Li; Wang, Yong; Li, Xudong; Oberholzer, José

doi:10.1016/j.jmbbm.2020.103636

Cited by 9 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[31] Previously, we showed that a loading of 0.5 MPa, 1 Hz, 1.5 h daily caused a typical degenerative phenotype in mouse discs. [22] In this study, our loading magnitude (0.02 MPa) and duration (1.5 hr day −1 ) were both smaller and shorter than most of the literature reported values, while our loading frequency (1 Hz) was higher than other studies. Due to the variation in the loading protocols across studies, mechanical regimens on animal discs should be discussed on a case-by-case basis.…”

Section: Computational Simulation Of Mechanical Loadingcontrasting

confidence: 68%

“…[ 21 ] In a separate study, an automated multi‐throughput mechanical system was also built to allow axial compression on mouse discs with a wide range of loading regimens, such as magnitude, frequency, cycle, and duration. [ 22 ] However, this mechanical loading system could not sustain tissue integrity and cell viability of mouse disc after 7 days of in vitro culture, since the force sensitive resistor (FSR) was not sensitive enough to accurately detect compression force lower than 0.05 MPa delivered to mouse discs. In this study, we aim to establish a microfluidic organ culture system “Intervertebral Disc‐on‐a‐Chip MF ”—an integrated platform that allows for simultaneous mechanical loading (“M” for mechanical ) and continuous media supply (“F” for flow ) to study the long‐term impacts of nutrients and mechanical loading on disc structure and homeostasis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

Xie,

Xing,

Xiao

et al. 2023

Adv Materials Technologies

Self Cite

View full text Add to dashboard Cite

This study aims to develop an ex vivo organ‐on‐a‐chip model, intervertebral Disc‐on‐a‐ChipMF, to investigate integrated effects of mechanical loading and nutrition on disc health. The system consists of a detachable multilayer microfluidic chip, a Computer‐Arduino‐based control system, and a mechanical loading unit, which are optimized for accurate axial force measurement and the maintenance of a 21‐day ex vivo disc culture. To ensure accuracy of axial force, the axial mechanical loading regimen is optimized, using the Computer‐Arduino‐based system and low‐profile force sensors (LPFS) to control the mechanical loading unit, and the force distribution on the disc surface is modeled by computational simulation. A 21‐day ex vivo disc culture is demonstrated using the Disc‐on‐a‐ChipMF system, with optimized mechanical loading (0.02 MPa at 1Hz, 1.5 hr day−1) and flow rate (1 µL min−1). The structural integrity, collagen breakdown, catabolic enzyme activities, and disc cell and collagen alignment reveal that the on‐chip cultured discs exhibit a preferred disc health similar to that of native discs for up to 21 days, while discs in a static culture show degenerative changes. The mouse Disc‐on‐a‐ChipMF system mimics in vivo disc microenvironment and provides a valuable platform for studying the effects of various factors on disc health and degeneration and testing new therapies.

show abstract

Section: Computational Simulation Of Mechanical Loadingcontrasting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

Xie,

Xing,

Xiao

et al. 2023

Adv Materials Technologies

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, Haqqi and colleagues showed that mitochondrial dysfunction in chondrocytes and cartilage explants from patients with OA increased the mitochondrial superoxide production, the expression of inflammatory factors, and the degradation of type II collagen in the cartilage matrix . Correlations of intervertebral disc degeneration with aging, inflammatory factors, dysregulated osmoadaptation, accumulation of AGEs (Figure a), , and ex vivo mechanical culturing conditions have been assessed histologically with CHPs to show the denatured collagen in the annulus fibrosus of the IVDs. The cornea and sclera are connective tissues formed by networks of collagen fibrils.…”

Section: Biology Of Collagen Hybridizationmentioning

confidence: 99%

The Chemistry and Biology of Collagen Hybridization

Zhang

et al. 2023

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Collagen provides mechanical and biological support for virtually all human tissues in the extracellular matrix (ECM). Its defining molecular structure, the triple-helix, could be damaged and denatured in disease and injuries. To probe collagen damage, the concept of collagen hybridization has been proposed, revised, and validated through a series of investigations reported as early as 1973: a collagen-mimicking peptide strand may form a hybrid triple-helix with the denatured chains of natural collagen but not the intact triple-helical collagen proteins, enabling assessment of proteolytic degradation or mechanical disruption to collagen within a tissue-of-interest. Here we describe the concept and development of collagen hybridization, summarize the decades of chemical investigations on rules underlying the collagen triple-helix folding, and discuss the growing biomedical evidence on collagen denaturation as a previously overlooked ECM signature for an array of conditions involving pathological tissue remodeling and mechanical injuries. Finally, we propose a series of emerging questions regarding the chemical and biological nature of collagen denaturation and highlight the diagnostic and therapeutic opportunities from its targeting.

show abstract

“…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%

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

A multi-throughput mechanical loading system for mouse intervertebral disc

Cited by 9 publications

References 38 publications

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

The Chemistry and Biology of Collagen Hybridization

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

Contact Info

Product

Resources

About

A multi-throughput mechanical loading system for mouse intervertebral disc

Cited by 9 publications

References 38 publications

Intervertebral Disc‐on‐a‐ChipMF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

Intervertebral Disc‐on‐a‐ChipMF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

The Chemistry and Biology of Collagen Hybridization

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

Contact Info

Product

Resources

About

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow

Intervertebral Disc‐on‐a‐Chip^MF: A New Model for Mouse Disc Culture via Integrating Mechanical Loading and Dynamic Media Flow