Flexible smart bandage for treating Infection and initiating wireless localized wound healing

Chronic non-healing wounds represent a major source of morbidity for patients and a significant economic burden. Wound infections are a leading cause of chronic non-healing wounds. It is estimated that wound infections occur in 15-25% of all wounds and result in morbidity (i.e., sepsis) and even mortality in vulnerable populations, such as diabetics. Current wound care treatments are generally passive and are unable to adapt to changes in the wound environment in real time. There remains a pressing need to develop therapeutic devices to rapidly detect and treat local wound infection before they become clinically obvious. Wearable devices are well positioned to address these challenges by integrating biosensors to detect wound infection and then deliver active wound care treatment without requiring the intervention of a physician. An ideal wound care technology would be able to (i) detect local wound infection at its earliest stages and (ii) automatically initiate treatment in a closed-loop fashion. By integrating multimodal sensors and adding stimulators in a bandage, real-time physiological monitoring is possible and provides an opportunity for active intervention into the complex wound environment. My central hypothesis is that delivering precise electrical stimulation in response to early infection can reduce bacterial bioburden, prevent overt infections and ultimately promoting wound healing. To do this, I will first examine the role of topical intervention on the wound healing process. I will look at the role of an iron chelator, namely deferoxamine (DFO), and its ability to reduce oxidative stress through the hypoxia-inducible factor-1 alpha (HIF-1α) pathway. I will then use cell-based therapies, namely ASCs, demonstrating that by enriching ASCs for pro-regenerative surface markers, dermal recovery is further augmented with greater number of pro-angiogenic genes and reduction of pro-inflammatory markers. Next, I will use a novel class of highly potent short synthetic hairpin RNA (sshRNA) integrated in a hydrogel to modulate the HIF-1α via prolyl hydroxylase domain-containing protein 2 (PHD2). I will demonstrate that intracellular silencing of both PHD2 as well as miR-210 enables improved wound healing outcomes. I will then look at regulation of various intracellular pathways involved in fibrosis and scarring, which is a common side effect of imbalanced wound healing, through various topical delivery methods. I will demonstrate that reduction of scarring and fibrosis can be enabled by the modulation of pathways involved in the wound healing cascade. Combining the above, I will then present a new method of modulating wound healing with topical intervention that enhances dermal recovery and reduces fibrosis, by using state-of-the-art technology, coupled with extensively studied wound healing biological responses. Combining sensing and stimulation modalities, I present a battery-free flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with tissue-interfacing tough conducting hydrogel electrodes for robust signal transduction, on-demand adhesion, and detachment. I demonstrate that this system can dynamically respond to an active wound environment, activating pro-regenerative genes and significantly improving wound healing outcomes

Keywords: Bioengineering.
Advisor: Gurtner Geoffrey
Altman Russ 
Snyder Michael