DOI: 10.5061/dryad.hdr7sqvpg
title: Soft robots with autonomous adaptation for effective drug delivery amidst fibrous encapsulation

description: 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.
description: # Soft robots with autonomous adaptation for effective drug delivery
 amidst fibrous encapsulation The necessary raw data is included and
 clearly labelled with examples: **Electrical impedance measurements were
 taken during animal study data - A1_Left_Device1_Day1_m1 etc.** A1 -
 animal Left - side of the animal device placed Device1 - device number
 Day1 - day measurement taken m1 - technical replicate **KNN classfier -
 *0.3agarose device1 repeat 1*(1) (etc.)** 0.3agarose - concentration of
 agarose device1 - device number repeat 1 - technical replicate **Comsol
 model - FSDSR_FCt_75um_Day7_Porosity0.8_Passive_timeS_Cmol_mm (etc.)**
 75um - capsule thickness day7 - day porosity0.8 - porosity passive -
 passive diffusion TriActN - actuated with a triangular pressure profile
 followed by number N of actuations over 10 min period RectActN - actuated
 with a rectangular pressure profile followed by number N of actuations
 over 10 min period timeS - denotes the values in the first column of the
 file is time (Sec) Cmol_mm - denotes the values in the second column of
 the file is the surface integral of the concentration in the region
 beneath the device with units (mol/mm)
 **Figure_3_PartD_Thickness_and_volume_of_fibrotic_capsule_averages
 (etc.)** diameter - diameter of capsule (mm) thickness - thickness of
 capsule (mm) volume - volume of capsule (mm^3) R2 - Pore resistance (Ohms)
 Rp - Log of fitted pore resistance (Ohms) ## Code/Software All code is
 intended to work in R and included here as .txt files. The code was used
 in Rmarkdown documents and might contain chunks to output a graph in the
 final report. The code provided cannot be used by itself as the import and
 averaging steps were not included. However, the code shows exactly the
 steps followed for each analysis, once the data had been imported and
 averaged.