Abstract
There is currently an interest in “active” implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibers that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses. In this study, it is shown that the shape changes induced in the scaffolds can be used to promote osteogenesis in vitro. In particular, immunofluorescence, gene and protein analyses reveal that the actuated networks exhibit higher mineralization and extracellular matrix production, and express higher levels of osteocalcin, alkaline phosphatase, collagen type 1α1, runt-related transcription factor 2 and bone morphogenetic protein 2 than the static controls at the 3-week time point. The results suggest that the cells filling the inter-fiber spaces are able to sense and react to the magneto-mechanically induced strains facilitating osteogenic differentiation and maturation. This work provides evidence in support of using this approach to stimulate bone ingrowth around a device implanted in bone and can pave the way for further applications in bone tissue engineering.
Highlights
It has long been recognized that the factors governing the changes in bone structure around prosthetic implants are sensitive to microenvironmental cues, consisting of combinatorial biochemical and mechanical stimuli [1,2]
We show for the first time that this type of actuation increases matrix production, mineralization, and osteogenic gene and protein expression in human osteoblasts cultured onto ferromagnetic fiber networks
There was a concomitant increase in the amount of bone morphogenetic protein 2 (BMP-2) and osteocalcin produced by the cells and enhanced deposition of mineralized matrix. These results demonstrate that the strains produced during magneto-mechanical actuation of ferromagnetic fiber networks can increase the in vitro osteogenic differentiation of human osteoblasts growing within the networks
Summary
It has long been recognized that the factors governing the changes in bone structure around prosthetic implants are sensitive to microenvironmental cues, consisting of combinatorial biochemical and mechanical stimuli [1,2]. The literature devoted to understanding how mechanical stimuli (fluid flow shear stress, hydrostatic pressure, and deformation by induced stresses/strains) are converted into biochemical signals and are integrated into cellular responses is vast. Cellular responses have been explained by various mechanotransduction models involving integrin-mediated adhesions and stress activated ion channels [6,7,8].
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