Stretch, as a form of mechanical force,plays a crucial role in regulating cell behaviors, preventing injuries andrepairing tissues such as lung, heart, brain and skeletal system. Among them,stretch in bone tissues has captured the most immense attention in clinicalapplications, for bone tissues are continuously exposed to stretch stimulationduring physiological activities. The structure and function of bone tissuesrelies on a proper amount of stretch stimulation, while lack of exercises tendsto result in the reduction of bone volume and osteoporosis. Under physiologicalconditions, bone tissues are subjected to micro-stretch with a variable frequency.
Although there has been a massive body ofresearch into the effects of stretch stimulation with a constant frequency, thebiological effects of micro-stretch with a variable frequency have not yet beenidentified. Moreover, commercial stretching devices are unable to generatestretch with a variable frequency similar to the in vivo condition of bonetissues. Against this backdrop, the research team led by Prof. OUYANG Hongweiproposed a novel cell stretcher, named as “musical dish”, which for the first timeused the conversion of musical signals to mechanical signals to realize theregulation of stem cell fate by micro-stretch with a variable frequency (NUMS).Their research findings were published in Bioengineering & TranslationalMedicine, entitled “‘Musical dish’ efficiently induces osteogenicdifferentiation of mesenchymal stem cells through music derived micro-stretchwith variable frequency”.
In this study, the researchers developed amusical dish with fast response, large deformation, optical transparency androbust controllability, based on dielectric elastomer actuators (DEAs) . Thismusical dish could convert musical signals into electrical ones, which could befurther converted into mechanical energy via a flexible dielectric elastomermembrane. It could trigger stretching stably. The actuating strain was featuredby homogeneity and equiaxiality. When cells were seeded on the musical dish,they could proliferate normally. The cells showed displacement with theincrease of the voltage. To evaluate the effect of NUMS, 1 kV constant voltagewith musical signals was applied to cells. The stretch ranged from 0.833% to0.867% which is close to the stretch condition in bone tissues. Quantitativeanalysis revealed that cells in the NUMS group exhibited more markedfilamentous stress fibers than constant stretch and no stretch groups. Bonedevelopment and ossification were up-regulated according to the gene ontology(GO) enrichment analysis. Further, Experiments identified a significantincrease in the expression of bone cell-related genes under NUMS, but theexpression of stemness-related genes decreased tremendously. The NUMS alsopromoted osteogenic differentiation of cells in induction medium. These findings highlight a novel “musicaldish”, which allows arbitrary strain waveforms to be applied to cells byconverting music signals into the stretching force. In comparison with constantstretching, NUMS may have great potential for promoting bone differentiation ofcells. For clinical applications, three strategies may contribute to thedevelopment of potential therapeutic ways for bone regeneration. First, NUMScould be used in the distraction osteogenesis surgery to replace or assist thecurrent large-scale and slow stretching method for bone regeneration due to itssuperb performance in promoting osteogenic differentiation. Second, the musicaldish could be further developed into a music-derived rehabilitation technologyto promote bone healing. Finally, the musical dish could serve as a cellexpansion bioreactor to produce cells with a high level of osteogenicdifferentiation to repair bones by transplantation. Thus, both the newstretching model and the newly-developed stretching device may have a brilliantclinical prospect.
