Luteolin (LUT) is a brilliant anti-inflammatory drug having a potential role in wound healing. Nevertheless, its clinical application is inadequate due to its hydrophobicity and poor skin permeation. Pressure ulcers are chronic wounds that have limited and definite treatments. This work aimed to develop a LUT-zein nanocomposite in a bioactive polymeric scaffold as a topical treatment for pressure ulcer wounds by assessing its effect on the pressure ulcers' immune microenvironment. LUT loaded scaffolds were prepared and evaluated regarding particle size, zeta potential, swelling & erosion capacity. Structure elucidation was performed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The scaffold (F6) that utilized hyaluronic acid (HA) and sodium alginate (SA) in a concentration of 4:1 revealed the most promising results and it was selected for the in vivo studies. The scaffold (F6) showed a nanosize (240.00 ± 8.54 nm) and a negative ZP (-38.2 ± 2.49 mV). SEM revealed a vastly porous structure in both cross-sections and surface views. In vivo wound healing potential and histological study were evaluated using male Sprague Dawley rats. This is the first study to design LUT-Zn nanpcomposite loaded in HA/SA scaffolds to enhance healing rate and decrease ulcer formation. The selected scaffold showed superior efficacy in modulating the immune microenvironment of the pressure ulcer wound in-vivo as it significantly inhibited IL17A secretion, upregulated IL13 and VEGF, increased miRNA-223 expression, and reduced cell apoptosis within the wound microenvironment, making it a promising treatment for chronic pressure ulcers. The elaborated F6 scaffold could be considered as a talented nanotherapy for enhanced pressure ulcer healing and wound closure rate.
