**6. New strategies for "wound targeted revascularization"**

**5. Contemporary landmarks in ischemic wounds revascularization**

recently described [29, 74, 75].

258 Wound Healing - New insights into Ancient Challenges

29, 35, 60, 72].

treatment [29, 35].

barriers [1, 29, 75, 81–86].

Expanding clinical evidence in the last three decades supports both bypass and the endovascular techniques as useful strategies in CLI revascularization [1–3, 29–31]. Providing low invasiveness, high reproducibility, and comparable limb salvage rate to open surgery [21–73], transcatheter strategies continue to evolve with new low-profile and high-performance devices in arterial reconstruction [21, 29, 74]. For most "high-risk" CLI patients [1, 2, 31, 34], new endovascular approaches and techniques were designed. In succinct overview, the "drilling," the "subintimal," or the "parallel wire" techniques via the ante- or retrograde accesses, the pedal-plantar "loop," and the femoral-femoral or transtibial collaterals angioplasties were

Not with standing with these spectacular transcatheter performances, the "classical" bypass for distal leg reperfusion is still imposed as a fundamental technique for CLI diabetic foot revascularization, tissue healing, and limb preservation [1, 3, 72, 76]. High-skill distal vein bypasses to the tibial [72], to the pedal [77], and up to the plantar or tarsal foot arteries [78] equally by targeting remote branches of pedal arteries in some particular cases [1, 76] were successfully documented. We now know that both surgical and endovascular techniques are more likely complementary than competitive techniques since each of them holds major advantages and inherent drawbacks [1, 29, 30, 79]. Endovascular techniques essentially provide minimal invasiveness, great accessibility, and reproducibility for one or multiple below-the-knee CTO recanalizations [1, 29, 73–75]. Alternatively, bypass offers a higher pressure on targeted arteries and more physiological and pulsatile flow inside collaterals around the wound zone [35, 53, 77–79]. This particularity heightens arterial-arterial collateral shear stress and enhances rising arteriogenesis [58–60] toward further tissue cicatrization [1,

Although still heterogeneously structured [1, 73, 79], increasing contemporary clinical observation documents equivalent limb salvage, clinical success, and survival outcomes for bypass versus endoluminal interventions in selected groups of CLI patients [1–3, 27, 29–31, 79, 80]. Notwithstanding with initial historical considerations [79], these two strategies appear nowadays more intricate than ever inside the conceptualized "team approach" as CLI

Parallel advances concerning the DFS revascularization and ischemic wound healing were equally testified in the last two decades [1, 2, 75]. Beyond striking surgical arterial reconstructions [76–79], new tapered nitinol [81], drug-eluting stents (DES) [82], and original drugeluting balloon, (DEB) [83] were imagined. Novel or redesigned directional or rotational atherectomy devices [84], together with latest "bioresorbable scaffolds" technologies [85], represent few additional of numerous achievements that challenge today ancient technical The complex cascade of tissue regeneration needs precise circumstances to unfold [85]. Beyond high-performance techniques in reconstructing arterial flow [72–86], new strategies about "when" and "where" to perform appropriate revascularization emerge today [1, 27, 30, 35]. Contemporary practitioners equally avail key data on the molecular mechanisms generating ischemic threat and tissue regeneration [59–61]. This knowledge, part of a larger "integrated multidisciplinary medicine" [87, 88], supports new strategies in limb salvage [1, 29, 48] based on precise arterial flow mapping [23–26] and deliberate tissue healing reengineering [29–31]. A new conceptualization of ischemic wound treatment rises at present [1, 2, 33], with promising serviceableness in patient's stratification [47, 53, 57, 59], revascularization selection [35, 38], and dedicated postoperative follow-up [31].

According to this modern emphasis, novel "hybrid" surgical and endovascular techniques [89], synchronous ante- and retrograde arterial accesses [74, 90], and novel topographic "wound-directed" revascularization (WDR) [24, 35, 91–93] proved useful to save more limbs for major amputation. Alternatively, extreme venous limb arterialization [94, 95] and cell stem treatment [1, 29] parallel to rising "multidisciplinary team" practice [57, 87, 88] have also been developed and seem to revolutionize previous CLI paradigms of care [1, 29, 92–94].
