Monitoring oxygen in healing wounds       

There is a great need to improve wound healing in many patients, and this is likely to occur through a better understanding of key factors affecting the process. Oxygen is perhaps the most important variable in the healing of wounds, as has been shown empirically in patients and more specifically in animal models. With appropriate methods, animal models can be used to understand the fundamental molecular biology and physiology that affects wound healing. In collaboration with groups at UCSF and The U. of Texas Medical Branch at Galveston, we have been using the capabilities of EPR oximetry to measure oxygen in wounds repeatedly to understand basic phenomena involved in wound healing. It has become clear that in addition to being a very useful technique for studying wounds in animal models, it is quite feasible to adapt the technique to clinical applications. The latter would enable clinicians to monitor the status of healing wounds so that intervention could be implemented promptly when the conditions for healing were becoming suboptimal. Both groups have models and techniques in current use that would permit the use of oximetric EPR materials to be present in the wounds in gas permeable biocompatible containers, thereby making it feasible to utilize the capabilities of in vivo EPR oximetry without the necessity of the long complex procedures for testing and approval of a new diagnostic drug by the FDA, which would be required if the oximetric materials were to be put directly into tissues.

The plans to move this approach to clinic are to complete development the EPR oximetry techniques to make repeated measurements at several sites within the wound models, using the material (Lithium phthalocyanine, LiPc) and the techniques that will be used clinically. The LiPc will be incorporated securely into the device that will go into the wound or will be enclosed in gas permeable biocompatible small capsules that can be removed after healing. We will measure pO₂ at several sites to obtain measurements at different depths and positions within the wound, using standard multisite techniques. The LiPc will sample pO₂ at various sites within the tubing wall, providing data from specific points, which can be collected as often as desired, including kinetic data when potential modifying procedures are used (e.g. alterations in the content of the breathing gas, administration of vasoactive drugs).

There also are some interesting possibilities of using spin trapping to explore the postulated roles of oxidative damage in some basic aspects of wound healing and in the response to therapy. For example, there are concerns that an oversupply of oxygen could have a negative impact on wound healing, either through direct damage or by affecting cell signaling that is needed for effective repair. In vivo spin trapping may be an effective way to approach some of the relevant experimental questions. Of particular interest is the effect on the oxygen tension within the wound of currently utilized modalities thought to speed wound healing.

The ability of EPR oximetry to make repeated measurements from localized sites provides a very important capability that can enable critical aspects of research on wound healing to go forward. The value and feasibility of the collaborations already have been demonstrated. There is significant promise that this approach can be a valuable tool in the clinical management of healing wounds, defining clinical parameters and end points leading to optimized utilization of expensive therapies.

EPR Center for the Study of Viable Systems