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Active tissue adhesive activates mechanosensors and prevents muscle atrophy

Nature Materials volume 22, pages 249–259 (2023)Cite this article

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Abstract

While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel–elastomer–nitinol tissue adhesive (MAGENTA) that generates and delivers muscle-contraction-mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of a shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein and myocardin-related transcription factor A, and increases the rate of muscle protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating the prevention of atrophy. MAGENTA thus has promising applications in the treatment of muscle atrophy and regenerative medicine.

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Fig. 1: MAGENTA provides mechanical stimulation to the target tissue.
Fig. 2: Mechanical and thermal performance of soft actuators and prediction of tissue deformation.
Fig. 3: Ex vivo and in vivo application of MAGENTA.
Fig. 4: Mechanical stimulation by MAGENTA activates mechanosensors and increases protein synthesis in disuse muscles.
Fig. 5: Mechanical stimulation by MAGENTA delays the occurrence of muscle atrophy, maintaining muscle size and weight and muscle function.
Fig. 6: Wireless, remote-controllable MAGENTA with a laser.

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Data availability

Data supporting the findings of this study are available in the Article and its Supplementary Information, and deposited at https://doi.org/10.7910/DVN/C3G80C. Unprocessed Western blots are provided in the Supplementary Information. Source data are provided with this paper.

Code availability

The custom code for controlling the actuation of MAGENTA is available at https://github.com/sungminnam/MAGENTAcode/blob/main/MAGENTA.

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Acknowledgements

This work was supported by the National Institute of Dental and Craniofacial Research (R01DE013349), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD086843) and the National Science Foundation’s Materials Research Science and Engineering Center at Harvard University (DMR14-20570). S.N. gratefully acknowledges funding support from the Wyss Technology Development Fellowship. A.J.N. acknowledges a Graduate Research Fellowship from the National Science Foundation. S.L.M. acknowledges funding support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (F31AR075367). Additionally, we thank Mooney Laboratory members for helpful discussions. We thank Dana-Farber/Harvard Cancer Center in Boston, Massachusetts, for the use of the Rodent Histopathology Core.

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Authors and Affiliations

  1. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Sungmin Nam, Bo Ri Seo, Alexander J. Najibi, Stephanie L. McNamara & David J. Mooney

  2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

    Sungmin Nam, Bo Ri Seo, Alexander J. Najibi, Stephanie L. McNamara & David J. Mooney

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Contributions

S.N., B.R.S. and D.J.M. conceived the study and designed the experiments. S.N., B.R.S., A.J.N. and S.L.M. carried out the experiments. S.N. performed the computational simulations. S.N. and D.J.M. wrote the manuscript.

Corresponding author

Correspondence to David J. Mooney.

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Competing interests

S.N. and D.J.M. are inventors on a patent application on the active adhesives utilized in this study (US patent application no. 63/299,433; Filed, January, 2022).

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Nature Materials thanks Xuanhe Zhao and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–24, Tables 1 and 2, Methods, notes, video legends and references.

Reporting Summary

Supplementary Video 1

The actuation of a soft actuator controlled by voltage.

Supplementary Video 2

T-peeling tests for an elastomer–hydrogel interface.

Supplementary Video 3

T-peeling tests for a hydrogel–tissue interface.

Supplementary Video 4

Deformation of a phantom tissue by the actuation of MAGENTA (top view).

Supplementary Video 5

Deformation of a phantom tissue by the actuation of MAGENTA (side view).

Supplementary Video 6

Ex vivo application of MAGENTA.

Supplementary Video 7

Peeling off MAGENTA from the tissue after the 420th actuation.

Supplementary Video 8

In vivo application of MAGENTA and its actuation.

Supplementary Video 9

High-frequency ultrasound imaging during the actuation of MAGENTA.

Supplementary Video 10

Actuation of wireless soft actuators by laser irradiation.

Supplementary Video 11

In vivo application of wireless remote-controlled MAGENTA.

Supplementary Video 12

Laser irradiation through ~1 mm porcine skin to wireless MAGENTA.

Supplementary Video 13

Laser irradiation through ~2 mm mouse muscle to wireless MAGENTA.

Source data

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Source data for Fig. 3.

Source Data Fig. 4

Source data for Fig. 4.

Source Data Fig. 5

Source data for Fig. 5.

Source Data Fig. 6

Source data for Fig. 6.

Source Data Fig. 4

Uncropped blots.

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Nam, S., Seo, B.R., Najibi, A.J. et al. Active tissue adhesive activates mechanosensors and prevents muscle atrophy. Nat. Mater. 22, 249–259 (2023). https://doi.org/10.1038/s41563-022-01396-x

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