• Zehnder, Anna-Katharina
• Schädli, Gian Nutal
• Rubert, Marina
• Müller, Ralph
• Leeuw, Anke De
• Lai, Yuxiao
• Zeng, Peng
• Zhang, Jianhua
• Griesbach, Julia
• Ganeyev, Marsel

Abstract

<jats:title>Abstract</jats:title><jats:p>Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation <jats:italic>in vivo</jats:italic>. However, the influence of mechanical stimulation on the formation of bone organoid <jats:italic>in vitro</jats:italic> is not clearly understood. Here, three-dimensional (3D) bioprinted human mesenchymal stem cells-laden graphene oxide composite scaffolds were cultured in a novel cyclic-loading bioreactors for up to 56 d. Our results showed that mechanical loading from day 1 (ML01) significantly increased organoid mineral density, organoid stiffness, and osteoblast differentiation compared with non-loading and mechanical loading from day 21. Importantly, ML01 stimulated collagen I maturation, osteocyte differentiation, lacunar-canalicular network formation and YAP expression on day 56. These finding are the first to reveal that long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids. Such 3D bone organoids may serve as a human-specific alternative to animal testing for the study of bone pathophysiology and drug screening.</jats:p>

Topics

• density
• impedance spectroscopy
• mineral
• composite