Targeting Programmed Cell Death in Flap Ischemia/Reperfusion Injury

A skin flap is a composite tissue unit comprising skin and subcutaneous fat with an intact vascular supply. Skin flaps are commonly employed for wound reconstruction, transplantation of damaged tissues, and cosmetic procedures. However, flap necrosis resulting from ischemia/reperfusion injury (IRI) is a frequent complication, leading to surgical failure. Therefore, This review systematically summarizes the mechanisms and therapeutic interventions targeting specific modalities of programmed cell death (PCD) in the context of IRI compromising flap survival. These interventions encompass a range of strategies, including preconditioning, systemic administration, and local drug delivery. Furthermore, we summarize key therapeutic targets for various types of PCD, along with shared pathways and therapies applicable across multiple PCD modalities. The findings presented in this review validate the feasibility of targeted therapies against PCD to prevent post-reconstructive flap necrosis. These findings provide novel strategies, such as targeting common pathways in PCD and leveraging diverse biomaterials, to enhance therapeutic outcomes. Further clinical investigations are warranted to target PCD pathways for the treatment of flap necrosis.