(WHS-P19) Fluoxetine delivery through an integrated bioelectronic device promotes wound healing in swine
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
Epidermal wound healing, including hemostasis, inflammation, cell proliferation, cell migration, and tissue remodeling, is a highly coordinated biological process. To optimally promote wound closure by a temporally and spatially controlled drug delivery system, a team of bio- and electrical engineers, computer scientists and wound specialists collaborated to create this iontophoresis bandage device with an actuator for drug delivery, and a sensor for wound monitoring. Previously we have demonstrated that this bioengineered device with programmable bioelectronic ion pumps to release protonized fluoxetine in neglibible amount of solution, can increase re-epithelialization and decrease macrophage M1/M2 ratio on mouse wounds. Here we further integrated an actuator, the fluoxetine iontophoresis bandage, and a sensor, a microscopic camera with LED lights, onto a single platform with on-board PCB electronics and wireless communication on the device for the in vivo swine tests. Full-thickness, 20mm circular wounds were created on the back of Yorkshire pigs and the fluoxetine device with camera was applied to the wounds. Fluoxetine was targeted to deliver 0.45mg/wound/day during the daily delivery program. On the post-operative days 3 or 7, wound tissue was harvested to examine healing. On day 7, the treatment with fluoxetine device showed a trend of improved re-epithelialization by 50.4% compared to standard of care (n=6-8 wounds, p=0.056). The anti-inflammatory macrophage M2 subtype also increased with the fluoxetine device treatment, which results in decreased ratios of M1/M2 by 77.0 % on day 3 and by 62.5 % on day 7. Another indication of the tissue repair is innervation to the wound site. By using the expression of MAP2, Microtubule-Associated Protein 2, as a surrogate marker for neuronal ingrowth and dendrite extension into the wound, we demonstrated that the relative gene expression of MAP2 for fluoxetine-treated wounds on day 7 was 0.9 compared to 0.2 for the control, a 4.5-fold increase on wound edge. The integrated bioelectronic device with fluoxetine delivery has a great potential for wound treatment by reducing the burden for daily drug application, and possibly increasing patients’ compliance. It also demonstrates that the fluoxetine released from the device retains its reparative biological activity to promote healing. In the future, we hope to further optimize the device design for the next stage of development for device commercialization and clinical use.