Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Abstract

Marine polysaccharides are believed to be promising wound-dressing nanomaterials because of their biocompatibility, antibacterial and hemostatic activity, and ability to easily shape into transparent films, hydrogels, and porous foams that can provide a moist micro-environment and adsorb exudates. Current efforts are firmly focused on the preparation of novel polysaccharide-derived nanomaterials functionalized with chemical objects to meet the mechanical and biological requirements of ideal wound healing systems. In this contribution, we investigated the characteristics of six different cellulose-filled chitosan transparent films as potential factors that could help to accelerate wound healing. Both microcrystalline and nano-sized cellulose, as well as native and phosphorylated cellulose, were used as fillers to simultaneously elucidate the roles of size and functionalization. The assessment of their influences on hemostatic properties indicated that the tested nanocomposites shorten clotting times by affecting both the extrinsic and intrinsic pathways of the blood coagulation system. We also showed that all biocomposites have antioxidant capacity. Moreover, the cytotoxicity and genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. The nature of the cellulose used as a filler was found to influence their cytotoxicity at a relatively low level. Potential mechanisms of cytotoxicity were also investigated; only one (phosphorylated microcellulose-filled chitosan films) of the compounds tested produced reactive oxygen species (ROS) to a small extent, and some films reduced the level of ROS, probably due to their antioxidant properties. The transmembrane mitochondrial potential was very slightly lowered. These biocompatible films showed no genotoxicity, and very importantly for wound healing, most of them significantly accelerated migration of both fibroblasts and keratinocytes.

Deacetylation and Desuccinylation of the Fucose-Rich Polysaccharide Fucopol: Impact on Biopolymer Physical and Chemical Properties

“…The films’ transparency was 5.16 ± 1.09, a value higher than that reported for the native FucoPol films (3.67) [ 5 ], thus indicating that the deacetylation and desuccinylation of the polysaccharide slightly increased its film opacity [ 61 ]. Transparency is important in packaging applications, providing see through properties and preventing light transmission [ 62 , 63 ], and in wound dressings to accurately monitor wound healing [ 64 ]. The films’ complete solubilization when placed in water indicated the inexistence of cross-linking reactions [ 5 ].…”

Functional hemostatic hydrogels: design based on procoagulant principles

“…Furthermore, mesocellular silica was also used in the study due to its similar properties. 81,206 Notably, the FXII-mediated coagulation cascade is not triggered at low MCF concentrations. Besides, kaolin (the main component is aluminum silicate) can also initiate the coagulation reaction by activating FXII and has been used to make hemostatic hydrogels.…”

“…These investigations have heavily relied on the precise chemicals loaded for their intended purpose. This review describes these hydrogels according to three perspectives: initiation of the intrinsic pathway, 206 This journal is © The Royal Society of Chemistry 2024 Fig. 7 The coagulation cascade.…”

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects

“…The interaction of phosphorylated CS with charged biomaterials was investigated by Sperling et al [ 79 ] The phosphorylation of CS may improve the hemocompatibility of the CS surface, thereby promoting more cations to interact with factor V and factor XI. Furthermore, CS is also able to be modified by sulfhydryl groups, which facilitate the adsorption of red blood cells and platelets, increase the concentration of clotting factors at the bleeding site, and accelerate the hemostasis [ 80 ]. As shown in Figure 3 , using sulfhydryl-modified CS (CSS) as an efficient peptide cross-linking agent (EPLM), Nie et al [ 81 ] prepared a novel hemostatic hydrogel capable of rapid cross-linking by introducing maleimide groups to hydrolyzed lysine under mild conditions ( Figure 3 A–C).…”