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Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform

Author

Listed:
  • William Whyte

    (Massachusetts Institute of Technology)

  • Debkalpa Goswami

    (Massachusetts Institute of Technology)

  • Sophie X. Wang

    (Massachusetts Institute of Technology
    Beth Israel Deaconess Medical Center)

  • Yiling Fan

    (Massachusetts Institute of Technology)

  • Niamh A. Ward

    (Massachusetts Institute of Technology
    National University of Ireland Galway)

  • Ruth E. Levey

    (National University of Ireland Galway)

  • Rachel Beatty

    (National University of Ireland Galway)

  • Scott T. Robinson

    (National University of Ireland Galway
    Trinity College Dublin)

  • Declan Sheppard

    (University Hospital)

  • Raymond O’Connor

    (National University of Ireland Galway)

  • David S. Monahan

    (Massachusetts Institute of Technology
    National University of Ireland Galway)

  • Lesley Trask

    (National University of Ireland Galway)

  • Keegan L. Mendez

    (Harvard-MIT Program in Health Sciences and Technology)

  • Claudia E. Varela

    (Harvard-MIT Program in Health Sciences and Technology)

  • Markus A. Horvath

    (Harvard-MIT Program in Health Sciences and Technology)

  • Robert Wylie

    (National University of Ireland Galway)

  • Joanne O’Dwyer

    (Massachusetts Institute of Technology
    National University of Ireland Galway)

  • Daniel A. Domingo-Lopez

    (National University of Ireland Galway)

  • Arielle S. Rothman

    (Massachusetts Institute of Technology)

  • Garry P. Duffy

    (National University of Ireland Galway
    Trinity College Dublin)

  • Eimear B. Dolan

    (National University of Ireland Galway)

  • Ellen T. Roche

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Harvard-MIT Program in Health Sciences and Technology)

Abstract

Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes.

Suggested Citation

  • William Whyte & Debkalpa Goswami & Sophie X. Wang & Yiling Fan & Niamh A. Ward & Ruth E. Levey & Rachel Beatty & Scott T. Robinson & Declan Sheppard & Raymond O’Connor & David S. Monahan & Lesley Tras, 2022. "Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32147-w
    DOI: 10.1038/s41467-022-32147-w
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    References listed on IDEAS

    as
    1. Kuen Yong Lee & Martin C. Peters & Kenneth W. Anderson & David J. Mooney, 2000. "Controlled growth factor release from synthetic extracellular matrices," Nature, Nature, vol. 408(6815), pages 998-1000, December.
    2. Donghui Zhang & Qi Chen & Yufang Bi & Haodong Zhang & Minzhang Chen & Jianglin Wan & Chao Shi & Wenjing Zhang & Junyu Zhang & Zhongqian Qiao & Jin Li & Shengfu Chen & Runhui Liu, 2021. "Bio-inspired poly-DL-serine materials resist the foreign-body response," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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