Ischemic skin flap viability: in vivo study of alginate-ZIF-8 hydrogel systems with Rhizophora mangle and tannic acid.

Abstract

Skin flaps are widely used in plastic and reconstructive surgery. However, inadequate blood perfusion during flap mobilization can trigger an ischemic process that may lead to tissue necrosis in the absence of effective management of the inflammatory process. In this context, the search for new biocompatible strategies to ensure the viability of ischemic skin flaps (ISFs) remains necessary. Therefore, this study evaluated novel alginate-ZIF-8 (ALG-ZIF-8) hydrogel systems with Rhizophora mangle (R. mangle) extract and tannic acid (TA) to assess their potential in preventing necrosis in ISF. Twenty-two male Wistar rats underwent the surgical creation of ISF and were divided into four groups: 0.9% saline (negative control - NegC), placebo alginate hydrogel (pALGgel), ALG-ZIF-8 hydrogel system with 5% TA (ALGzTA), and finally, ALG-ZIF-8 hydrogel system with 5% R. mangle (ALGzRm). Flap outcomes were evaluated through macroscopic observation, followed by morphometric analysis of viable and necrotic areas, and histomorphometric analysis of fibroblasts, blood vessels, and leukocytes, using ImageJ and PrimeCam 5.1 software. Statistical analysis was performed using IBM SPSS software (version 27). The results suggest that the formulations produced divergent outcomes by differentially modulating inflammatory and angiogenic responses. The ALGzRm formulation tended to show a protective profile, associated with a significant reduction in leukocyte infiltration (p < 0.001), while the ALGzTA formulation was linked to a detrimental response, including exacerbated inflammation and a pathologically high blood vessel count (p = 0.015). In conclusion, findings suggest that the ALGzRm-gel has a potential for tissue repair, mediated by the modulation of inflammatory and angiogenic responses.