Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform
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s41467-022-32147-w.pdf
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2.65 MB
Format
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Checksum (MD5)
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Author(s)
Whyte, William
Goswami, Debkalpa
Wang, Sophie X.
Fan, Yiling
Ward, Niamh A.
Levey, Ruth E.
Beatty, Rachel
Robinson, Scott T.
Sheppard, Declan
O’Connor, Raymond
Date Issued
August 3, 2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Whyte, W., Goswami, D., Wang, S.X. et al. Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform. Nat Commun 13, 4496 (2022).
Version
Final published version
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.
Subjects
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
General Chemistry
Multidisciplinary
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Mechanical Engineering
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1038/s41467-022-32147-w
