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A novel system for dynamic stretching of cell cultures reveals the mechanobiology for delivering better negative pressure wound therapy

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Abstract

Serious wounds, both chronic and acute (e.g., surgical), are among the most common, expensive and difficult-to-treat health problems. Negative pressure wound therapy (NPWT) is considered a mainstream procedure for treating both wound types. Soft tissue deformation stimuli are the crux of NPWT, enhancing cell proliferation and migration from peri-wound tissues which contributes to healing. We developed a dynamic stretching device (DSD) contained in a miniature incubator for applying controlled deformations to fibroblast wound assays. Prior to the stretching experiments, fibroblasts were seeded in 6-well culture plates with elastic substrata and let to reach confluency. Squashing damage was then induced at the culture centers, and the DSD was activated to deliver stretching regimes that represented common clinical NPWT protocols at two peak strain levels, 0.5% and 3%. Analyses of the normalized maximal migration rate (MMR) data for the collective cell movement revealed that for the 3% strain level, the normalized MMR of cultures subjected to a 0.1 Hz stretch frequency regime was ~ 1.4 times and statistically significantly greater (p < 0.05) than that of the cultures subjected to no-stretch (control) or to static stretch (2nd control). Correspondingly, analysis of the time to gap closure data indicated that the closure time of the wound assays subjected to the 0.1 Hz regime was ~ 30% shorter than that of the cultures subjected to the control regimes (p < 0.05). Other simulated NPWT protocols did not emerge as superior to the controls. The present method and system are a powerful platform for further revealing the mechanobiology of NPWT and for improving this technology.

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Acknowledgements

We would like to thank Mr. Jelle van Orsouw from Eindhoven University of Technology and Dr. Uri Zaretsky from our Department of Biomedical Engineering at Tel Aviv University for their help regarding the development of the cell stretching apparatus and experimental work. This research work was partially supported by the Israel Science Foundation Grant No. 1266/16 and by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant Agreement No. 811965.

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  1. The Herbert J. Berman Chair in Vascular Bioengineering, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 6997801, Tel Aviv, Israel

    Rona Katzengold, Alexey Orlov & Amit Gefen

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  1. Rona Katzengold
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  3. Amit Gefen
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Correspondence to Amit Gefen.

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Katzengold, R., Orlov, A. & Gefen, A. A novel system for dynamic stretching of cell cultures reveals the mechanobiology for delivering better negative pressure wound therapy. Biomech Model Mechanobiol 20, 193–204 (2021). https://doi.org/10.1007/s10237-020-01377-6

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