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Local stimulation of osteocytes using a magnetically actuated oscillating beam.

ABSTRACT: Mechanical loading on bone tissue is an important physiological stimulus that plays a key role in bone growth, fracture repair, and treatment of bone diseases. Osteocytes (bone cells embedded in bone matrix) are well accepted as the sensor cells to mechanical loading and play a critical role in regulating the bone structure in response to mechanical loading. To understand the response of osteocytes to differential mechanical stimulation in physiologically relevant arrangements, there is a need for a platform which can locally stimulate bone cells with different levels of fluid shear stress. In this study, we developed a device aiming to achieve non-contact local mechanical stimulation of osteocytes with a magnetically actuated beam that generates the fluid shear stresses encountered in vivo. The stimulating beam was made from a composite of magnetic powder and polymer, where a magnetic field was used to precisely oscillate the beam in the horizontal plane. The beam is placed above a cell-seeded surface with an estimated gap height of 5 ?m. Finite element simulations were performed to quantify the shear stress values and to generate a shear stress map in the region of interest. Osteocytes were seeded on the device and were stimulated while their intracellular calcium responses were quantified and correlated with their position and local shear stress value. We observed that cells closer to the oscillating beam respond earlier compared to cells further away from the local shear stress gradient generated by the oscillating beam. We have demonstrated the capability of our device to mimic the propagation of calcium signalling to osteocytes outside of the stimulatory region. This device will allow for future studies of osteocyte network signalling with a physiologically accurate localized shear stress gradient.

SUBMITTER: Onaizah O

PROVIDER: S-EPMC7323988 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Local stimulation of osteocytes using a magnetically actuated oscillating beam.

Onaizah Onaizah O Xu Liangcheng L Middleton Kevin K You Lidan L Diller Eric E

PloS one 20200629 6

Mechanical loading on bone tissue is an important physiological stimulus that plays a key role in bone growth, fracture repair, and treatment of bone diseases. Osteocytes (bone cells embedded in bone matrix) are well accepted as the sensor cells to mechanical loading and play a critical role in regulating the bone structure in response to mechanical loading. To understand the response of osteocytes to differential mechanical stimulation in physiologically relevant arrangements, there is a need f ...[more]

PMID: 32598396

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Project description:Providing the right stimulatory conditions resulting in efficient tissue promoting microenvironment in vitro and in vivo is one of the ultimate goals in tissue development for regenerative medicine. It has been shown that in addition to molecular signals (e.g. growth factors) physical cues are also required for generation of functional cell constructs. These cues are particularly relevant to engineering of biological tissues, within which mechanical stress activates mechano-sensitive receptors, initiating biochemical pathways which lead to the production of functionally mature tissue. Uniform magnetic fields coupled with magnetizable nanoparticles embedded within three dimensional (3D) scaffold structures remotely create transient physical forces that can be transferrable to cells present in close proximity to the nanoparticles. This study investigated the hypothesis that magnetically responsive alginate scaffold can undergo reversible shape deformation due to alignment of scaffold's walls in a uniform magnetic field. Using custom made Helmholtz coil setup adapted to an Atomic Force Microscope we monitored changes in matrix dimensions in situ as a function of applied magnetic field, concentration of magnetic particles within the scaffold wall structure and rigidity of the matrix. Our results show that magnetically responsive scaffolds exposed to an externally applied time-varying uniform magnetic field undergo a reversible shape deformation. This indicates on possibility of generating bending/stretching forces that may exert a mechanical effect on cells due to alternating pattern of scaffold wall alignment and relaxation. We suggest that the matrix structure deformation is produced by immobilized magnetic nanoparticles within the matrix walls resulting in a collective alignment of scaffold walls upon magnetization. The estimated mechanical force that can be imparted on cells grown on the scaffold wall at experimental conditions is in the order of 1 pN, which correlates well with reported threshold to induce mechanotransduction effects on cellular level. This work is our next step in understanding of how to accurately create proper stimulatory microenvironment for promotion of cellular organization to form mature tissue engineered constructs.

Dataset Information

Local stimulation of osteocytes using a magnetically actuated oscillating beam.

Publications

Local stimulation of osteocytes using a magnetically actuated oscillating beam.

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