Researching the Molecular Biology of Non-Healing Wounds

Currently, more than half of diabetic foot ulcers fail to heal with standard care. In Dr. Harold Brem’s wound healing program, we believe that we can revolutionize the field of wound healing by developing medical markers that predict which patients are likely to heal with standard care, and which patients will need specialized treatment to overcome their individual healing impediments. Therefore, a major objective of our clinical research is to identify the first objective biochemical and molecular markers capable of differentiating those diabetic foot ulcers and other chronic wounds that have the capacity to heal from those that don’t. Such markers have the potential to:

Several years ago, Dr. Brem’s laboratory made a fundamental breakthrough in wound healing when we demonstrated that people with diabetes have intrinsic healing deficits that inhibit the body’s ability to repair skin wounds by restoring normal skin at the wound site. This means that even with the best possible care, any diabetic foot ulcers these patients develop are less likely to undergo prompt and complete healing. These deficits include abnormalities in growth factors, cell function, and restoration of the complex matrix of normal skin structure. We also discovered that the areas around the edge of non-healing wounds that are infected and unable to start the healing process have characteristic abnormalities in tissue structure, protein expression and gene activity—abnormalities that clearly demonstrate they have an intrinsic healing defect. When this rim of healing-impaired tissue is removed from the edge of a chronic wound, the cellular healing process is then able to commence.

In the course of this research we identified a number of candidate biochemical and molecular markers that are involved in the fundamental biological wound repair process, and that may prove to be useful as predictors of healing potential. To help track this healing process, we developed objective quantitative measures of healing that we can use to evaluate clinical wound repair progress, study healing mechanisms, and test new targeted treatments.

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