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In vitromodel to study confined osteocyte networks exposed to flow-induced mechanical stimuli.

ABSTRACT: Osteocytes are considered the primary mechanical sensor in bone tissue and orchestrate the coupled bone remodeling activity of adjacent osteoblast and osteoclast cells.In vivoinvestigation of mechanically induced signal propagation through networks of interconnected osteocytes is confounded by their confinement within the mineralized bone matrix, which cannot be modeled in conventional culture systems. In this study, we developed a new model that mimics thisin vivoconfinement using gelatin methacrylate (GelMA) hydrogel or GelMA mineralized using osteoblast-like model cells. This model also enables real-time optical examination of osteocyte calcium (Ca²⁺) signaling dynamics in response to fluid shear stimuli cultured under confined conditions. Using this system, we discovered several distinct and previously undescribed patterns of Ca²⁺responses that vary across networks of interconnected osteocytes as a function of space, time and connectivity. Heterogeneity in Ca²⁺signaling may provide new insights into bone remodeling in response to mechanical loading. Overall, such a model can be extended to study signaling dynamics within cell networks exposed to flow-induced mechanical stimuli under confined conditions.

SUBMITTER: Zhang K

PROVIDER: S-EPMC10642715 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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In vitromodel to study confined osteocyte networks exposed to flow-induced mechanical stimuli.

Zhang Kairui K Ogando Courtney C Filip Alex A Zhang Teng T Horton Jason A JA Soman Pranav P

Biomedical materials (Bristol, England) 20221125 6

Osteocytes are considered the primary mechanical sensor in bone tissue and orchestrate the coupled bone remodeling activity of adjacent osteoblast and osteoclast cells.In vivoinvestigation of mechanically induced signal propagation through networks of interconnected osteocytes is confounded by their confinement within the mineralized bone matrix, which cannot be modeled in conventional culture systems. In this study, we developed a new model that mimics thisin vivoconfinement using ...[more]

PMID: 36384043

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Project description:The vestibular end-organs encode for linear and angular head accelerations in space contributing to our internal representation of self-motion. Activation of the vestibular system with transmastoid electrical current has recently grown in popularity; however, a direct relationship between electrically evoked and mechanically evoked vestibular responses remains elusive in humans. We have developed and tested a mechanical-to-electrical vestibular stimulus conversion model incorporating physiological activation of primary vestibular afferents identified in nonhuman primates. We compared ocular torsional responses between mechanical (chair rotation) and model-derived electrical (binaural-bipolar) stimuli in separate experiments for an angular velocity step change (±10 deg/s over 1 s, ±4-mA peak amplitude; n = 10) and multisine angular velocities (±10 deg/s, 9.7 mA peak to peak, 0.05-1 Hz; n = 5), respectively. Perception of whole body rotation (n = 18) to our step-change stimuli was also evaluated. Ocular torsional slow-phase velocity responses between stimulation types were similar (paired two one-sided tests of equivalence: multiple P < 0.002; one-sample t test: P = 0.178) and correlated (Pearson's coefficient: multiple P < 0.001). Bootstrap analysis of perceived angular velocity likewise showed similarity in perceptual decay dynamics. These data suggest that central processing between stimuli was similar, and our vestibular stimulus conversion model with a conversion factor of ∼0.4 mA per deg/s for an angular velocity step change can generate electrical stimuli that replicates dynamic vestibular activation elicited by mechanical whole body rotations. This proposed vestibular conversion model represents an initial framework for using electrical stimuli to generate mechanically equivalent activation of primary vestibular afferents for use in biomedical applications and immersive reality technologies.NEW & NOTEWORTHY With the growing popularity of electrical vestibular stimulation in biomedical and immersive reality applications, a direct conversion model between electrical and mechanical vestibular stimuli is needed. We developed a model to generate electrical stimuli mimicking the physiological activation of vestibular afferents evoked by mechanical rotations. Ocular and perceptual responses evoked by mechanical and model-derived electrical stimuli were similar, thus providing a critical first step toward generation of electrically induced vestibular responses that have a realistic mechanical equivalent.

Dataset Information

In vitromodel to study confined osteocyte networks exposed to flow-induced mechanical stimuli.

Publications

<i>In vitro</i>model to study confined osteocyte networks exposed to flow-induced mechanical stimuli.

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