Implantable Real Time Oxygen Biosensors for Detection of Vascular Perfusion and Ischemia
Mohamed M. Ibrahim, MD1, Ryan M. Schweller, PhD2, Mahmoud M. Mohammed, B.Eng1, David B. Powers, MD, DMD1, Bruce Klitzman, PhD1.
1The Division of Plastic, Maxillofacial, and Oral Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC, USA, 2Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Even with vast improvements in techniques and instrumentation, tissue non-viability due to a lack of adequate perfusion and oxygenation still remains a problem in many surgical settings, including free tissue transfer and non-healing wounds. Similarly, during endotracheal intubation, endotracheal tube compression can lead to significant tongue necrosis, requiring extensive oral and maxillofacial reconstructive surgery. Unfortunately, this lack of adequate perfusion can only be assessed post-operatively, after the onset of tissue necrosis. Here we have developed a new materials-based oxygen biosensor that can be implanted intradermally, subcutaneously, and intramuscularly for deep and superficial measurements of tissue oxygen tension (TOT) in response to changes in perfusion and inspired oxygen. We demonstrate the ability to detect the implanted sensors in ex-vivo human skin and to accurately measure TOT in rodents at various tissue depths as well as the ability to detect ischemic events in vivo in swine tongue with high temporal resolution and real time monitoring.
Porphyrin-based sensors were incorporated into poly(ethylene glycol) diacrylate hydrogels. This formulation allows direct measurements of local oxygen concentrations through changes in the phosphorescence lifetime as well as imaging via porphyrin fluorescence. Sensors were fabricated to a size permitting delivery via an 18 gauge needle. To investigate tissue oxygen tension, sensors were implanted intradermally and subcutaneously in rats. Sensor activity was confirmed by modulating the inspired oxygen levels between 12% and 100%. Sensor modulation was confirmed at 3, 7, and 14 days post-implantation. Sensors were similarly implanted acutely in pigs to monitor TOT under anesthesia. To mimic ischemic events, sensors were directly injected at various depths in pig tongue which was then subject to tourniquet ischemia.
Oxygen sensors modulated as expected to changes in oxygen levels. Similarly, in vivo TOT could be modulated from 0 to 110 mmHg by modulating the inspired oxygen between 12% and 100%. Sensors could also be detected in non-perfused, ex-vivo human skin via near-infrared fluorescence using an in vivo imaging system (IVIS). Both fluorescence and lifetime-based measurements could be obtained after at least 1 cm deep implantations. When implanted in pigs, sensors could be monitored at 5 anatomical implantation sites simultaneously and permitted real time monitoring of TOT during anesthesia and euthanasia. In swine tongue, sensors were able to immediately detect the application and release of tourniquet, occluding the sublingual artery.
Overall, our work has shown a fast, efficient, and inexpensive method to monitor local changes in oxygen content in real time and detect induced ischemia and reperfusion. The implementation of such devices could represent a facile method to prevent tissue necrosis during free tissue transfer, endotracheal intubation, as well as many other transplant and reconstructive surgical procedures.
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