Regenerative Approach for Improving Flap Survival: Perspective of Angiogenesis

Flap reconstruction remains a cornerstone after oncologic resection, trauma, and complex wounds, yet partial necrosis, venous congestion, and delayed healing continue to drive morbidity and unplanned re-exploration. Even when macroscopic inflow and outflow are re-established, distal and border-zone tissue may remain constrained by microcirculatory dysfunction. This review frames flap compromise as a biomimetics-relevant failure of a hierarchical transport network and summarizes the vascular repair mechanisms that regenerative interventions aim to replicate. We outline key concepts governing flap perfusion, including angiosomes, choke vessels, endothelial barrier failure, mural cell support, and immune regulation within the angiogenic niche, and relate these to no-reflow, thrombo-inflammation, and impaired vascular regeneration. We then synthesize regenerative strategies aimed at durable reperfusion, spanning recombinant factors, gene and nucleic acid delivery, cell-based therapies, cell-free biologics, including extracellular vesicles and platelet-derived products, pharmacologic modulators, and biomaterial platforms that localize and sustain bioactivity. Translation will require functional perfusion endpoints, standardized reporting of delivery parameters, and safety-conscious designs that minimize aberrant angiogenesis and vector-related risks in post-resection settings.