Microfluidic Bandage for Localized Oxygen-Enhanced Wound Healing Zameer H. Merchant, Joe F. Lo, David T. Eddington Biological Microsystems Lab, Department of Bioengineering, University of Illinois at Chicago

Importance of Oxygen in Wound Healing Oxygen – hyperoxic conditions1,2 02 is converted to Reactive Oxygen Species (ROS) Required for bactericidal activity Key step in wound healing pathway in low concentrations Topical oxygen accelerates angiogenesis by inducing production of Vascular Endothelial Growth Factor (VEGF) Induces collagen deposition and the tensile strength of skin May trigger the differentiation of fibroblasts to myofibroblasts, cells responsible for wound contraction. Franz Michael G, "Chapter 6. Wound Healing" (Chapter). Doherty GM: CURRENT Diagnosis & Treatment: Surgery, 13e: http://www.accessmedicine.com/content.aspx?aID=5211734. Gordillo, G., & Sen, C. (2003). Revisiting the essential role of oxygen in wound healing. The American Journal of Surgery , 186, 259-263.

Oxygen-Enhanced Wound Healing Techniques Current Future1 Portable device: available bedside and at home Localized to wound site Rapid diffusion of oxygen Inexpensive Can deliver oxygen directly to superficial wounded tissue severed from circulation No risk of multi-organ oxygen toxicity Hyperbaric Oxygen Therapy (HBO) Topical Oxygen Therapy Gordillo, G., & Sen, C. (2003). Revisiting the essential role of oxygen in wound healing. The American Journal of Surgery , 186, 259-263.

Microfluidic Bandage

Device Fabrication Photolithography

Device Fabrication

Measuring Oxygen Diffusion Calculation of [O2] after diffusion through PDMS membrane FOXY slide (ruthenium-coated oxygen-sensing chip) O2 quenches ruthenium fluorescence intensity Calibration curve established by exposing FOXY slide to known oxygen concentrations Data empirically fit to a Stern-Volmer model Oxygen-sensing chip

Characterization: Oxygen Modulation

Characterization: Oxygen Penetration Determine the “effective” range of oxygen penetration into tissue directly beneath the PDMS membrane Extent of oxygen penetration measured using phantom tissue (3% agarose) Depth of phantom tissue varied between 0.2 and 1.0mm Diffused oxygen concentration measured 5 minutes after device was connected to 100% O2 gas line Measured diffused oxygen concentration here

Characterization: Oxygen Penetration

Non-Conformal Bandage Characterization: Localization of O2 Delivery in Conformal and Non-conformal Devices Conformal Bandage Non-Conformal Bandage Chamber PDMS Obstacle PDMS Membrane

Characterization: Localization of O2 Delivery in Conformal and Non-conformal Devices

SKH1 Mice Wound Healing Day 3 Day 7 Day 10 Day 14 0 Day after wounding Device Placebo Control

SKH1 Mice Wound Healing

Conclusions Can consistently deliver 0.02 ±0.73 to 99.5± 4.40% O2 Can maintain localized oxygen delivery to a specified area even with a non-planar irregularity Can deliver ~80% O2 through 0.8 mm of agar tissue phantom within 5 minutes Device is compatible with normal wound healing Can be used to provide oxygen-enhanced wound treatment

Acknowledgments Financial support from the National Science Foundation and Department of Defense, EEC-NSF Grant # 0755115 Professor David T. Eddington – Biological Microsystems Lab, UIC Dr. Joe F. Lo Dr. DiPietro – Center for Wound Healing, UIC Dr. Christos Takoudis and Dr. Greg Jursich