Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery

胶囊 药物输送 生物医学工程 体内 材料科学 纳米技术 医学 生物 植物 生物技术
作者
Rachel Beatty,Keegan Mendez,Lucien H. J. Schreiber,Ruth Tarpey,William Whyte,Yiling Fan,Scott T. Robinson,Joanne O’Dwyer,Andrew J. Simpkin,Joseph Tannian,Peter Dockery,Eimear B. Dolan,Ellen T. Roche,Garry P. Duffy
出处
期刊:Science robotics [American Association for the Advancement of Science (AAAS)]
卷期号:8 (81) 被引量:16
标识
DOI:10.1126/scirobotics.abq4821
摘要

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 effects 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 fibrotic 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 after impedance measurements by the FibroSensing membrane. By sensing fibrotic 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 signals, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrotic capsule formation.
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