Long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids. (1st July 2022)

• Record Type: Journal Article
• Authors: Zhang, Jianhua; Griesbach, Julia; Ganeyev, Marsel; Zehnder, Anna-Katharina; Zeng, Peng; Schädli, Gian Nutal; Leeuw, Anke de; Lai, Yuxiao; Rubert, Marina; Müller, Ralph
• Is Part Of: Biofabrication. Volume 14:Number 3(2022)
• Publication Date: 2022-07-01
• Subjects: 3D bioprinting -- mechanical loading -- functional bone organoid -- osteoblast–osteocyte differentiation -- lacuna-canaliculi network; Biomedical engineering -- Periodicals; Tissue engineering -- Periodicals; Biomedical materials -- Microstructure -- Periodicals; Bioengineering -- Periodicals; 610.28
• DOI: 10.1088/1758-5090/ac73b9
• Languages: English
• ISSNs: 1758-5082

Abstract

Abstract: Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation in vivo . However, the influence of mechanical stimulation on the formation of bone organoid in vitro 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.