Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions

doi:10.1016/j.msec.2021.112313

. 2021 Sep:128:112313.

doi: 10.1016/j.msec.2021.112313. Epub 2021 Jul 14.

Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions

Akhilandeshwari Ravichandran¹, Christoph Meinert², Onur Bas³, Dietmar W Hutmacher⁴, Nathalie Bock⁵

Affiliations

¹ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia.
² Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Metro North Hospital and Health Service, Herston 4029, QLD, Australia.
³ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, QUT, Kelvin Grove 4059, QLD, Australia.
⁴ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia; Bone and Joint Disorders Program, School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane 4000, QLD, Australia; School of Biomedical Sciences, Faculty of Health and Australian Prostate Cancer Research Centre (APCRC-Q), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane 4000, QLD, Australia.
⁵ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia; School of Biomedical Sciences, Faculty of Health and Australian Prostate Cancer Research Centre (APCRC-Q), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane 4000, QLD, Australia; ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing, QUT, Kelvin Grove 4059, QLD, Australia. Electronic address: n.bock@qut.edu.au.

PMID: 34474864
DOI: 10.1016/j.msec.2021.112313

Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions

Akhilandeshwari Ravichandran et al. Mater Sci Eng C Mater Biol Appl. 2021 Sep.

. 2021 Sep:128:112313.

doi: 10.1016/j.msec.2021.112313. Epub 2021 Jul 14.

Authors

Akhilandeshwari Ravichandran¹, Christoph Meinert², Onur Bas³, Dietmar W Hutmacher⁴, Nathalie Bock⁵

Affiliations

¹ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia.
² Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Metro North Hospital and Health Service, Herston 4029, QLD, Australia.
³ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, QUT, Kelvin Grove 4059, QLD, Australia.
⁴ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia; Bone and Joint Disorders Program, School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty (SEF), QUT, Brisbane 4000, QLD, Australia; School of Biomedical Sciences, Faculty of Health and Australian Prostate Cancer Research Centre (APCRC-Q), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane 4000, QLD, Australia.
⁵ Centre in Regenerative Medicine, IHBI, QUT, Kelvin Grove 4059, QLD, Australia; Translational Research Institute (TRI), QUT, Woolloongabba 4102, QLD, Australia; School of Biomedical Sciences, Faculty of Health and Australian Prostate Cancer Research Centre (APCRC-Q), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane 4000, QLD, Australia; ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing, QUT, Kelvin Grove 4059, QLD, Australia. Electronic address: n.bock@qut.edu.au.

PMID: 34474864
DOI: 10.1016/j.msec.2021.112313

Abstract

Tissue engineering strategies are widely used to model and study the bone marrow microenvironment in healthy and pathological conditions. Yet, while bone function highly depends on mechanical stimulation, the effects of biomechanical stimuli on the bone marrow niche, specifically on bone marrow adipose tissue (BMAT) is poorly understood due to a lack of representative in vitro loading models. Here, we engineered a BMAT analog made of a GelMA (gelatin methacryloyl) hydrogel/medical-grade polycaprolactone (mPCL) scaffold composite to structurally and biologically mimic key aspects of the bone marrow microenvironment, and exploited an innovative bioreactor to study the effects of mechanical loading. Highly reproducible BMAT analogs facilitated the successful adipogenesis of human mesenchymal bone marrow stem cells. Upon long-term intermittent stimulation (1 Hz, 2 h/day, 3 days/week, 3 weeks) in the novel bioreactor, cellular proliferation and lipid accumulation were similar to unloaded controls, yet there was a significant reduction in the secretion of adipokines including leptin and adiponectin, in line with clinical evidence of reduced adipokine expression following exercise/activity. Ultimately, this innovative loading platform combined with reproducibly engineered BMAT analogs provide opportunities to study marrow physiology in greater complexity as it accounts for the dynamic mechanical microenvironment context.

Keywords: Adipose tissue model; Biomechanical loading; Bioreactor; Composite; GelMA; Hydrogel.

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Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions

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Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions

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