(B-51) Drug Delivery Enabled Negative Pressure Wound Therapy Systems

Introduction:: Every year millions of Americans suffer from painful chronic wounds, skin injuries that fail to heal within three months. If left untreated, they can lead to amputation and even death. Chronic wounds cost the healthcare system upwards of $50 billion a year, and as aging and diabetic populations expand these wounds are expected to become more common. A commonly used clinical treatment for chronic wounds is negative pressure wound therapy (NPWT), which involves packing the injury with polyurethane foam, covering it with an adhesive drape, and then applying a vacuum. NPWT systems that infuse the foam with a solution are available, but so far limited to saline and antibacterials due to the high volume needed to flush the foam. To broaden the range of therapeutics that can be paired with NPWT systems, we explore active and passive release methods for delivering drugs through 3D printed and gelatin-based MNAs into the wound bed. In this work, we seek to improve on existing NPWT therapy systems by incorporating MNA-mediated drug delivery to allow for the delivery of therapeutics while the wound remains under vacuum.


Materials and Methods:: Hollow MNAs were 3D printed and connected to a peristaltic pump. Flow rate through the MNA was characterized by massing water as it was pushed through by the pump. Negative pressure and volumetric flow rate created by the vacuum pump at different voltages was measured with a pressure gage and by massing the water respectively. Drug delivery into an agarose skin phantom under vacuum was imaged over an hour period. To create hydrogel needles, positive MNA master-molds were 3D printed then cast in silicone rubber to create negative molds. A 15% porcine gelatin, 2% transglutaminase solution was pipetted into the molds, which were centrifuged to remove bubbles. Enzymatic crosslinking was allowed to proceed for 2 hours before samples were dessicated. Passive release of BSA-FITC from gel samples into PBS was measured using fluorescent signal in a plate reader. Murine model animal studies are ongoing.


Results, Conclusions, and Discussions::
For the active release system, flow rate through the hollow needles could be controlled by changing the voltage applied to the peristaltic pump (Figure 1a), and the ability to rapidly switch on and off was demonstrated (Figure 1b). The vacuum pump was found to reach its maximum pressure when supplied 5V, before reaching a plateau (Figure 1c), which allows us to avoid excessive voltage in the system. The volumetric flow rate shows a more continuous increase with increase in voltage, but even at just 1V is pulling more than 20mL/s, which would be more than sufficient for even a highly exudative wound (Figure 1d). The ability to deliver drugs while using negative pressure was determined by pumping into an agarose skin phantom (Figure 1e), and it was demonstrated that the drug was penetrating and being maintained in the gel even under vacuum. For the passive release, fabricated needle arrays underwent release testing and showed an expected burst release in the first day, followed by a slower release until the end of the four-day test period (Figure 1f). Our past work has shown that gel concentration, level of crosslinking, and other factors allow for tuning of the release profile. Animal testing for these systems is ongoing at this time. In this study, we aim to address a major limitations of existing NPWT systems, drug delivery during application of negative pressure. We present two strategies for improving drug delivery, one active and one passive, that both utilize microneedles to target drug release past any surface barriers commonly seen in these kinds of injuries. Chronic wounds are called a silent epidemic, with their high mortality rate often unrecognized. Here we hope to improve on current clinical systems to increase wound resolution rates, save limbs, and save lives.


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