Diabetic Foot Ulcer (DFU) Biofilm Infection and Recurrence

Diabetic foot ulcers (DFU) are one of the most common reasons for hospitalization of diabetic patients and frequently results in amputation of lower limbs. Of the one million people who undergo non-traumatic leg amputations annually worldwide, 75% are performed on people who have type 2 diabetes (T2DM). The risk of death at 10 years for a diabetic with DFU is twice as high as the risk for a patient without a DFU. The rate of amputation in patients with DFU is 38.4%4. Infection is a common (>50%) complication of DFU. Emerging evidence underscores the significant risk that biofilm infection poses to the non-healing DFU. Biofilms are estimated to account for 60% of chronic wound infections. In the biofilm form, bacteria are in a dormant metabolic state. Thus, standard clinical techniques like the colony forming unit (CFU) assay to detect infection may not detect biofilm infection. Thus, biofilm infection may be viewed as a silent maleficent threat in wound care.

n the current standard of care (SoC), wound closure is defined (FDA) by wound area re-epithelialization without drainage. The investigators' pre-clinical large animal work demonstrates that wounds with a history of biofilm infection may meet above criteria, but the repaired wound-site skin is deficient in barrier function. This has led to the concept of functional wound closure wherein the current clinical definition of wound closure is supplemented with a functional parameter - restoration of skin barrier function as measured by low trans-epidermal water loss (TEWL).

This study rests pilot study showing that closed DFU with deficient barrier function are more likely to recur. Biofilm infection as assessed through scanning electron microscopy and wheat germ agglutin assay performed on debrided tissue causes faulty re-epithelialization, compromising skin barrier function at the closed wound site. This work is based on DFU patients, seeks to conduct a fully powered clinical study testing i) If DFU with a history of biofilm infection closes with deficient barrier function. ii) whether such functionally deficient wound closure, manifested as high TEWL, is associated with greater wound recurrence. The primary parent study will also address molecular mechanisms implicated in biofilm-induced loss of skin epithelial barrier integrity in DFU patients.

Inclusion criteria

• Male or Female, Age ≥ 18
• Willing to comply with protocol instructions, including all study visits and study activities.
• Patient with an open Diabetic Foot Ulcer
• Adequate arterial blood flow as evidenced by at least one of the following (for wounds below the knee):
• TcOM >30 mmHg
• Ankle-brachial index at least ≥0.7
• Toe pressure > 30 mmHg
• TBI > 0.6 mmHg

Exclusion criteria

• Individuals who are deemed unable to understand the procedures, risks, and benefits of the study.
• Wounds closed or to be surgically closed by flap or graft coverage
• Subjects with marked immunodeficiency (HIV/AIDS, or on immunosuppressive medications.
• TcOM < 30mmHg
• Diabetics with a hemoglobin A1c > 15 within 3 months prior to enrollment
• Subject with autoimmune connective tissue disease
• Ulcer size and location that does not allow the TEWL measurement per SOP
• Pregnant women
• Prisoners
• Unable to comply with study procedures and/or complete study visits