Prostacyclin (PGI2) Pathway to Enhance Wound Healing in Diabetic Foot Ulcers

Inclusion criteria: Groups 1,2,3,4: * Informed consent signed * Affiliated to social security insurance or beneficiary of social security insurance * Aged of 18 or older Group 1: healthy volunteers: -Free from all acute and chronic pathology Group 2: diabetic patients without DFU: -Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA), without DFU or history of DFU Group 3: diabetic patients with DFU or recent history of DFU (occurred within the last two years): -Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA) with: One or more active grade 1A, 1C, 2A or 2C (University of Texas Classification of Diabetic Foot) foot ulcer of microvascular or mixed etiology; Or a recent history (\<2 years) of foot ulcer of microvascular or mixed etiology. Group 4 (to collect samples of foot skin biopsies to address secondary objectives ): -Patients with type 2 diabetes according to the criteria of the American Diabetes Association (ADA),with neuropathy and DFU undergoing lower-limb surgery for skin ulcer (e.g. toe amputation). Exclusion criteria Groups 1, 2 and 3: * Unstable diabetes that has resulted in hyperosmolar coma or ketoacidosis, and/or documented increase or decrease in HbA1c of more than 2.0% within the previous 3 months. * Presence of diabetic peripheral neuropathy above the ankle, defined as a scoring \>3 of at least two of the four stimuli of the Neuropathy Disability Score (i.e. pinprick sensation, light touch, vibration, and temperature perception) (37). * Infected wound, treated with antibiotics in the past 15 days. * Critical ischemia of the lower limb, defined as leg pain at rest associated with ankle pressure \<70 mmHg. * History of hypersensitivity reaction to treprostinil, fluconazole, other azole compounds, L-NMMA, ketorolac, meloxicam, or any NSAIDs or acetylsalicylic acid, lidocaine (or any local anesthetic with an amide bond), or their excipients * History of asthma, rhinitis, nasal polyps, angioedema, hives rash, or any other allergic reaction due to acetylsalicylic acid or any NSAID taking * Pulmonary veno-occlusive disease (PVOD) * Porphyria * Hyperkalemia * Active or uncontrolled cardiovascular disease as follows: Myocardial infarction, or angina within the previous 6 months; Severe ischemic heart disease; Arrhythmia (uncontrolled, symptomatic, requiring treatment or life-threatening); Congestive heart failure, or decompensated heart failure not medically controlled; Stroke or transient ischemic attack within the previous 3 months; Uncontrolled hypertension: systolic blood pressure (SBP)\> 180 mmHg or diastolic blood pressure (DBP)\> 105 mmHg (2 abnormal readings during visit) Valvular heart disease * Severe liver disease (Child-Pugh C) at the time of enrollment * Renal disease (creatinine \>2 mg/dL and/or estimated glomerular filtration rate (GFR) \<30 mL/min, history of dialysis) * Active peptic ulcer disease, recent gastrointestinal bleeding or perforation, or history of peptic ulcer disease or gastrointestinal bleeding or perforation with NSAIDs * Intracerebral or gastrointestinal hemorrhage, hemostasis disorder or every clinical status that may lead to bleeding * Chronic venous disease defined as stage 4a and 4b of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification * Cutaneous condition deemed incompatible with skin biopsy and dermal microdialysis by the investigator * History of necrotic angiodermatitis * Trauma or any clinical event susceptible to be responsible for hemorrhage within the previous 6 months * Concomitant treatment with pentoxifylline, anticoagulants, probenecid, medicinal products known to prolong the QT interval or anti-inflammatory or analgesic dose of acetylsalicylic acid * If concomitant treatment with NSAIDs, participants have to be stopped 1 week before the inclusion * Pregnancy or Lactation * Females with childbearing potential, defined as a premenopausal female capable of becoming pregnant, and not using an highly effective form of birth control. Effective birth control methods include: oral, implant or patch hormone contraception; intrauterine device; abstinence and outercourse; tubal ligation; vasectomy. Groups 1,2,3 and 4: * Participant involved in another interventional clinical study * Person deprived of liberty by judicial order * Person under guardianship or curatorship