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; Ellen T Roche

doi:10.1038/s41467-022-32147-w

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

Nat Commun. 2022 Aug 3;13(1):4496. doi: 10.1038/s41467-022-32147-w.

Authors

William Whyte^#¹, Debkalpa Goswami^#¹, Sophie X Wang^#^{1

2}, Yiling Fan³, Niamh A Ward^{1

4}, Ruth E Levey⁵, Rachel Beatty⁵, Scott T Robinson^{5

6}, Declan Sheppard⁷, Raymond O'Connor⁵, David S Monahan^{1

5}, Lesley Trask⁴, Keegan L Mendez⁸, Claudia E Varela⁸, Markus A Horvath⁸, Robert Wylie⁵, Joanne O'Dwyer^{1

4}, Daniel A Domingo-Lopez⁵, Arielle S Rothman¹, Garry P Duffy^{5

6}, Eimear B Dolan⁹, Ellen T Roche^{10

11

12}

Affiliations

¹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
³ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland.
⁵ Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.
⁶ Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland.
⁷ Department of Radiology, University Hospital, Galway, Ireland.
⁸ Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA.
⁹ Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland. eimear.dolan@nuigalway.ie.
¹⁰ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. etr@mit.edu.
¹¹ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. etr@mit.edu.
¹² Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA. etr@mit.edu.

^# Contributed equally.

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Drug Delivery Systems
Fibrosis
Foreign-Body Reaction
Humans
Longevity*
Prostheses and Implants*

Grants and funding

T32 HL007734/HL/NHLBI NIH HHS/United States