Responses of MSCs to 3D Scaffold Matrix Mechanical Properties under Oscillatory Perfusion Culture

Abstract

Both fluid shear stress and matrix stiffness are implicated in bone metabolism and functional adaptation, but the synergistic action of these mechanical cues on the biological behaviors of mesenchymal stem cells (MSCs) is still not well-known. In the present work, a homemade oscillatory flow device was applied to investigate the effects of matrix stiffness on MSCs survival, distribution, and osteogenic differentiation in three-dimensional (3D) conditions. Furthermore, the flow field and cell growth in this bioreactor were theoretically simulated. The results demonstrated that oscillatory shear stress significantly increased the viability and distribution uniformity of MSCs throughout the scaffold after culture for 3 weeks. Compared to static culture, oscillatory shear stress could promote the collagen secretion, mineral deposits, and osteogenic differentiation of MSCs. The findings obtained from this work indicate that the oscillatory perfusion not only provides a higher survival rate and a more uniform distribution of cells but also facilitates osteogenic differentiation of MSCs. Oscillating perfusion bioreactor culture of MSCs in 3D scaffold with optimal matrix stiffness could offer an easy-to-use but efficient bioreactor for bone tissue engineering.

Physical stimulations and their osteogenesis-inducing mechanisms

“…And the actin filaments rapidly reorganized into thick parallel bundles of fibres, and the fibre formation was induced by shear stress loading 0-90 min whereas the cytoskeleton was disrupted over loading 90 min ( Figure 3B ). Besides, fluid shear stress could produce bioeffects to cells which seeded on 3D printed bone scaffolds[ 95 , 96 ]. Stiehler et al .…”

“…Chen et al . [ 96 ] investigated synergistic action of fluid shear stress and three-dimensional porous scaffolds (collagen/ hydroxyapatite, Col/HA) on the biological behaviors of mesenchymal stem cells. The results showed that the viability of mesenchymal stem cells in the all scaffolds was significantly increased under oscillatory shear stress cultured for 3 weeks compared with control group.…”

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

“…Bone, one of the main mechanical supportive structures of the body, experiences various mechanical forces (e.g., gravity, locomotion, exercise, and external vibration) over the body’s whole life [ 2 , 3 , 4 ]. Mesenchymal stem cells (MSCs), osteoblasts, osteocytes, and osteoclasts, which are the main constituent cell types of bone, are stimulated by matrix stiffness, fluid shear stress, tension, and compression [ 5 , 6 , 7 , 8 ]. By sensing and responding to mechanical stimuli, bone cells adapt to the mechanical environment and maintain bone homeostasis [ 6 , 9 , 10 ].…”

“…Mesenchymal stem cells (MSCs), osteoblasts, osteocytes, and osteoclasts, which are the main constituent cell types of bone, are stimulated by matrix stiffness, fluid shear stress, tension, and compression [ 5 , 6 , 7 , 8 ]. By sensing and responding to mechanical stimuli, bone cells adapt to the mechanical environment and maintain bone homeostasis [ 6 , 9 , 10 ]. Moreover, chondrocytes, the primary cell type of cartilage that is also involved in bone development, are also stimulated by mechanical stimuli [ 11 ].…”

Biophysics Rules the Cell Culture but Has Yet to Reach the Clinic: Why Is That?

“…37,38 It is not a coincidence, after all, that exercise is an integral element of any orthopaedic rehabilitation regime. 39,40 Several bioreactor systems of variable complexity have been used as means to control tenocyte, 41 chondrocyte, 42 and osteoblast 43 phenotype in vitro and to direct stem cells toward tenogenic, 44 chondrogenic, 45 and osteogenic 46,47 lineages. Musculoskeletal tissues, like any other tissue, are highly dense ECM assemblies.…”