Pharmacological and cell-based treatments to increase local skin flap viability in animal models

Abstract

Local skin flaps are frequently employed for wound closure to address surgical, traumatic, congenital, or oncologic defects. (1) Despite their clinical utility, skin flaps may fail due to inadequate perfusion, ischemia/reperfusion injury (IRI), excessive cell death, and associated inflammatory response. (2) All of these factors contribute to skin flap necrosis in 10-15% of cases and represent a significant surgical challenge. (3, 4) Once flap necrosis occurs, it may require additional surgeries to remove the entire flap or repair the damage and secondary treatments for infection and disfiguration, which can be costly and painful. (5) In addition to employing appropriate surgical techniques and identifying healthy, well-vascularized tissue to mitigate the occurrence of these complications, there is growing interest in exploring cell-based and pharmacologic augmentation options. (6) These agents typically focus on preventing thrombosis and increasing vasodilation and angiogenesis while reducing inflammation and oxidative stress. Agents that modulate cell death pathways such as apoptosis and autophagy have also been investigated. (7) Implementation of drugs and cell lines with potentially beneficial properties have been proposed through various delivery techniques including systemic treatment, direct wound bed or flap injection, and topical application. This review summarizes pharmacologic- and cell-based interventions to augment skin flap viability in animal models, and discusses both translatability challenges facing these therapies and future directions in the field of skin flap augmentation.

Keywords: Cell-based therapy; Flap viability; Pharmacologic treatment; Skin flap.

Fig. 1

Therapeutics can be applied to skin flaps through various modalities. Six common modalities are visualized: oral, intravenous injection, intraperitoneal injection, subcutaneous injection, direct injection, and topical application. These are demonstrated on a murine McFarlane skin flap model

Fig. 2

Cell-based therapies require the harvest of cells from relevant tissue type and processing prior to usage as a therapy for skin flaps. The most common sources of these cells are adipose tissue, bone marrow, placental amniotic membrane, and the umbilical cord. These cells are typically applied to preclinical murine models via subcutaneous injection, as depicted in a McFarlane flap