FibroSensing Dynamic Soft Reservoir (FSDSR): A bio-sensing drug delivery device for monitoring the foreign body response in real time
Beatty, Rachel
Beatty, Rachel
Loading...
Repository DOI
Publication Date
2022-12-19
Type
Thesis
Downloads
Citation
Abstract
Despite significant advancements in Type 1 diabetes mellitus (Type 1 DM) treatments, the foreign body response continues to prevent the longevity of implantable medical devices that treat the condition. The development of a dense fibrotic capsule around implants leads to device seclusion and subsequent failure, which is detrimental for the function of biosensors and drug delivery devices. Strategies to prevent fibrous capsule growth have included material considerations, local delivery of anti-fibrotic drugs and cell therapies, however extensive room for improvement still exists. In this thesis, a new concept for modulating fibrotic capsule development was presented. Modulating the immune response to the implant could significantly improve the longevity of implantable medical technologies. First, it was shown the diabetic environment did not affect fibrotic capsule development to our soft robotic device called “dynamic soft reservoir” or DSR. Thereafter, using the next generation of the device called “soft transport augmenting reservoir” or STAR, it was shown that the device was capable of immunomodulating the developing capsule, while also maintaining drug delivery over 8 weeks in vivo. No change in total cell number (p = 0.700) was apparent but the neutrophil population was significantly reduced in the actuated group compared to the control at day 5 (p = 0.0098). This is important as neutrophils are one of the first responses in the foreign body response and play a major role in determining the extent of fibrosis which occurs. Both pre clinical testing and clinical translation of this system would benefit from an integrated method of real time monitoring of fibrous capsule development. A bio-sensing membrane called FibroSensing membrane was then developed, designed and validated. This membrane was capable of temporally monitoring the foreign body response both in vitro and in vivo using electrical impedance spectroscopy. This membrane was successfully implanted into a drug delivery device called the FibroSensing dynamic soft reservoir (FSDSR). Sensitivity of the FSDSR was proven in vitro with collagen deposition and myofibroblast proliferation resulting in an increase in sensor output. In vivo, capsular development was monitored over 7 days in a rodent model. The electrical resistance of the fibrotic capsule correlated to an increase in thickness and volume (Pearson’s coefficients 0.670 and 0.722). The use of the FibroSensing membrane to monitor the foreign body response in real time could ultimately be used as a feedback system to determine actuation regime to sustain drug delivery over time despite fibrotic encapsulation. By overcoming the limitations associated with implantable drug delivery devices, the treatment and management of Type 1 DM could be greatly improved
Funder
Publisher
NUI Galway