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Soft robots with autonomous adaptation for effective drug delivery amidst fibrous encapsulation

Dolan, Eimear1; Duffy, Garry2; Fan, Yiling3; Beatty, Rachel2; Whyte, William3; Robinson, Scott2; Roche, Ellen4; Mendez, Keegan4; Tarpey, Ruth1; ODwyer, Joanne1; Schreiber, Lucien1; Simpkin, Andrew1; Tannian, Joseph1; Dockery, Peter1

Published Mar 06, 2024 on Dryad. https://doi.org/10.5061/dryad.hdr7sqvpg

Data files

Mar 06, 2024 version files 11.52 MB

Abstract

The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its consequences via soft robotic actuations. Occlusion of the FSDSR porous membrane was monitored over 7 days in a rodent model using electrochemical impedance spectroscopy. The electrical resistance of the fibrotic capsule correlated to its increase in thickness and volume. Our FibroSensing membrane showed great sensitivity in detecting changes at the abiotic/biotic interface, such as collagen deposition and myofibroblast proliferation. The potential of the FSDSR to overcome fibrous capsule formation and maintain constant drug dosing over time was demonstrated in silico and in vitro. Controlled closed-loop release of methylene blue into agarose gels (with a comparable fold change in permeability relating to 7 and 28 days in vivo), was achieved by adjusting the magnitude and frequency of pneumatic actuations following impedance measurements by the FibroSensing membrane. By sensing fibrous capsule formation in vivo, the FSDSR will be capable of probing and adapting to the foreign body response through dynamic actuation changes. Informed by real-time sensor signal, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrous capsule formation.