In vitro bioreactor studies have shown that cyclic compression loads prompt osteoblast division, matrix production, and increase levels of alkaline phosphatase (ALP) activity, which result in an improvement of the compressive modulus of the entire structure.
The Wnt/β-Catenin canonical pathway is well established to be activated in response to mechanical stimulation, inducing downstream expression of secretory proteins, such as SPP1, and thereby influencing osteoblastogenesis and bone formation. Particularly, fluid shear stress has been shown to induce synthesis of non-collagenous proteins by osteoblasts, and therefore influence mineralization. These deformations are sensed by bone resident cells, namely, osteoblasts and osteocytes, through their ion channels and/or cell membrane receptors (e.g., transmembrane integrins and cadherins) and transduced into intracellular biochemical signals in a process known as mechanotransduction. In fact, bone tissue is mainly subjected to two types of mechanical signals: (1) strain caused by tension or compression triggered by physical activity, and (2) shear stress as a result of interstitial fluid movement through bone lacunae. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.ĮCM is, in principle, a very dynamic structure that controls and is controlled by its surrounding environment, adapting its structural arrangement and composition to external stimuli. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls.
In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected.