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Objectives: Foot ulceration associated with diabetic foot disease (DFD) and chronic limb-threatening ischaemia (CLTI) presents a complex clinical challenge and failure to heal the wound imposes a significant risk of major limb amputation (MLA). In attempt to accelerate wound healing rates and decrease MLA, tissue engineering research into bio-engineered scaffolds and skin substitutes has become a growing area of interest. Advanced wound therapies such as fetal bovine acellular dermal matrix (FBADM) may have success in the treatment of difficult to heal chronic foot ulcers. The FBADM traps and binds the patients' own epithelial cells to rebuild the dermis layer of the skin. Previous studies have suggested that wounds treated with FBADM had a faster healing rate than wounds managed with conventional dressings. However, these studies excluded foot wounds with chronic exposed bone or tendon, active infection, gangrene, or osteomyelitis and patients with uncontrolled blood glucose levels were excluded. The aim of this study was to assess the efficacy of FBADM for patients admitted to hospital acutely with severe foot ulceration secondary to DFD and CLTI. Methods: Between February 2020 and December 2021, inpatients admitted acutely at a single tertiary centre with a severe non-healing foot ulcer and had a wound suitable for application of a FBADM after primary debridement were included in the study. A severe non-healing foot wound was defined as a Society for Vascular Surgery Wound, Ischaemia, and foot Infection (WIfI) stage of 3 or 4. Participants were prospectively followed up at regular intervals at a multidisciplinary high-risk diabetic foot clinic until June 2022. The primary endpoint was time to wound closure. The secondary endpoints were number of applications of FBADM, readmission rate and amputation-free survival. Results: There were 22 patients included in the study with a median age of 71 (50–87) years and 15 were male. Five patients had a WIfI stage of 3 and 17 had a WIfI score of 4. Overall, 14 patients required revascularisation procedures (6 open surgery,8 endovascular intervention). A total of 18 patients achieved complete wound healing with a median time to wound healing of 178 (28–397) days. Two patients underwent a MLA and two patients died prior to complete wound healing. The median length of stay was 16.5 (5–115) days, and 4 patients were readmitted to hospital within 12 months. Conclusion: FBADM may be a useful adjunct in the acute setting of complex DFD and CLTI ulceration to assist with wound healing. Future comparative prospective studies are required to further validate these preliminary findings. [ABSTRACT FROM AUTHOR]