The patients will be recruited from the doctors and the nurses of the foot clinic of Department of Endocrinology. A complete medical history and physical parameters will be collected, moreover a peripheral circulation status will assess at the time of the enrolment. During the first visit blood samples and a biopsy from the site of foot ulcers will be taken together with a picture of the ulcer. All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding). Intervals between visits will range between 4 to 8 weeks according to the usual medical routine. During visits 1, 2 and 3 the ulcers status will be documented by pictures, physical parameter collected, biopsies, ulcer fluid and blood samples will be taken for further analysis.

At visit 3 the ulcers will be classified as "healing" if completely resolved or dramatically reduced (more than 50%), otherwise will be classified as "non-healing".

The patients will be recruited from the doctors and the nurses of the foot clinic of Department of Endocrinology. A complete medical history and physical parameters will be collected, moreover a peripheral circulation status will assess at the time of the enrolment. During the first visit blood samples and a biopsy from the site of foot ulcers will be taken together with a picture of the ulcer. All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding). Intervals between visits will range between 4 to 8 weeks according to the usual medical routine. During visits 1, 2 and 3 the ulcers status will be documented by pictures, physical parameter collected, biopsies, ulcer fluid and blood samples will be taken for further analysis.

At visit 3 the ulcers will be classified as "non-healing" if not resolved or not dramatically reduced (more than 50%).

All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding) according to the best standard of care

An aliquot of peripheral blood mononuclear cells obtained from patients at the first visit will be used to perform single-cell RNA-sequencing. Transcriptomic results of patients with healing ulcers will be compared with those with non-healing ulcers in order to identify different circulating monocytes populations only present in non-healing diabetic patients.

A freshly taken punch biopsy take from patient at visit 1 will be dissociated to a cell suspension. Single cell RNA sequencing analysis will be performed on these cells in order to study different cell populations. Bioinformatic analysis of sequenced data will identify macrophage's population, map cell heterogeneity and identify specific cell signature of healing compared to non-healing ulcers.

Moreover, by comparing the transcriptomic signature of the cell populations in the tissue with circulating monocytes population defined in aim 1, researchers will verify whether specific populations are already present in circulation or appearing once the cells are in the tissue, or derived skin-resident macrophages.