Novel, standardized pre-clinical surgical animal model to investigate the cellular and molecular mechanisms of ischemic flap healing

Abstract

Abstract Background Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled flaps and free autologous tissue transfer. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability.Results We present a novel, economical, and standardized pre-clinical animal model of excisional full-thickness wound closure and healing using axial pattern flaps that incorporates an anatomically named vascular pedicle. In this bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, which simulates an actual clinical procedure of autologous tissue transfer, one flap heals under normal and a contralateral flap - under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. Although we describe step-by-step methodological approach how to create such flaps as well as collect, process, and analyze flap survival data in larger size rodents, specifically, the rats (Rattus norvegicus), the BEFAF model is transferable and could be implemented in any mammalian species. We also stress the importance of taking and presenting high resolution histological stain images of the flaps that are indispensable for diagnostic result interpretation in the full-thickness wound healing studies.Conclusions BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury and interventions simulating clinically relevant flap complications (e.g., secondary arterial, venous, or mixed ischemia) and therapeutic or surgical treatments (e.g., flap delay) in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). This technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAF also serves as an aid for teaching basic vascular microsurgery techniques that focus on precision, tremor management and magnification.