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

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 Trask, Keegan L. Mendez, Claudia E. Varela, Markus A. Horvath, Robert Wylie, Joanne O’Dwyer, Daniel A. Domingo-Lopez, Arielle S. Rothman, Garry P. Duffy, Eimear B. Dolan () and Ellen T. Roche ()
Additional contact information
William Whyte: Massachusetts Institute of Technology
Debkalpa Goswami: Massachusetts Institute of Technology
Sophie X. Wang: Massachusetts Institute of Technology
Yiling Fan: Massachusetts Institute of Technology
Niamh A. Ward: Massachusetts Institute of Technology
Ruth E. Levey: National University of Ireland Galway
Rachel Beatty: National University of Ireland Galway
Scott T. Robinson: National University of Ireland Galway
Declan Sheppard: University Hospital
Raymond O’Connor: National University of Ireland Galway
David S. Monahan: Massachusetts Institute of Technology
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
Daniel A. Domingo-Lopez: National University of Ireland Galway
Arielle S. Rothman: Massachusetts Institute of Technology
Garry P. Duffy: National University of Ireland Galway
Eimear B. Dolan: National University of Ireland Galway
Ellen T. Roche: Massachusetts Institute of Technology

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32147-w

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