Diabetic foot ulcers and other chronic wounds are characterized by an accumulation of devitalized tissue, cellular exudates, and infection at their outer surface. These factors prevent healthy cells from responding adequately and stimulating wound healing. In order to facilitate the restoration and regeneration of damaged tissue in a wound, patients often undergo debridement, which is a process that removes devitalized tissue from the wound bed. Proper debridement of an ulcer is invaluable in facilitating a good clinical outcome.
However, in contrast to tumor excision and other surgical procedures, until recently there have been no objective biological markers that can be used to determine whether adequate debridement has occurred. Instead, surgeons are taught to “debride until it bleeds,” which is not optimal for such a crucial procedure.
Dr. Harold Brem’s research team has found that cells of a wound exhibit a specific pattern of gene activity. At the non-healing edge, cells are activated in a way that is detrimental to healing. These cells are unable to migrate appropriately, and they are different on molecular level from healthy cells. Additionally, they do not respond appropriately to wound healing stimuli. By contrast, the adjacent tissue on the healing edge contains cells that have an increased ability to migrate and that look physically similar to healthy cells. These cells also show a strong response to wound healing stimuli. Research has shown that the non-healing edge and the healing edge possess distinct gene expression profiles. For example, while one gene is turned on in the healing edge, it is turned off in the non-healing edge, contributing to the overall failure of 40% of patients to heal.
These gene expression profiles can be used in a clinical setting to determine whether a wound has been successfully debrided. In the same way that clinicians are able to test a tissue biopsy in order to confirm that all cancerous cells have been removed, our research helps to create a model in which surgeons can confirm that all of the non-healing tissue has been removed from a wound. Once the unhealthy tissue has been fully removed, the wound will be more susceptible to other therapeutic agents that would have been futile if applied to non-healing tissue.