**5. Possible future research**

We need many prospective, clinical trials targeting the reduction of unnecessary (systemic and topical) antibiotic use, assessing the value of antibiotic stewardship programs, and developing evidence-based guidance. We should also be interested in microbiomes and new therapies. We want to target unanswered questions and advance research in all aspects of DFO. For example, regarding neo-vascularization, one future hope lies in stem cells. Knowing that a subset of human monocytes expresses TIE-2, we could enhance neovascularization, since ischemia is a major concomitant problem to chronic DFO. We successfully extracted high numbers of proangiogenic TIE-2 monocytes from venous blood of diabetic patients without ischemia [73]. Likewise, current scientific achievements confirm the feasibility of amplifying adipose stem cells for angiogenesis from the abdominal fat of ischemic patients [74]. The implication of these findings in terms of autologous injections for therapeutic neo-angiogenesis will require further studies. DFO will remain a "never-ending challenge" [75].
