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

Autor: Whyte W; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Goswami D; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Wang SX; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Fan Y; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Ward NA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland., Levey RE; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., Beatty R; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., Robinson ST; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.; Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland., Sheppard D; Department of Radiology, University Hospital, Galway, Ireland., O'Connor R; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., Monahan DS; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., Trask L; Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland., Mendez KL; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA., Varela CE; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA., Horvath MA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA., Wylie R; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., O'Dwyer J; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland., Domingo-Lopez DA; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland., Rothman AS; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Duffy GP; Anatomy and Regenerative Medicine Institute (REMEDI), National University of Ireland Galway, Galway, Ireland.; Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland., Dolan EB; Department of Biomedical Engineering, National University of Ireland Galway, Galway, Ireland. eimear.dolan@nuigalway.ie., Roche ET; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. etr@mit.edu.; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. etr@mit.edu.; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, USA. etr@mit.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 03; Vol. 13 (1), pp. 4496. Date of Electronic Publication: 2022 Aug 03.
DOI: 10.1038/s41467-022-32147-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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