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Preparation and Characterization of an Injectable and Photo-Responsive Chitosan Methacrylate/Graphene Oxide Hydrogel: Potential Applications in Bone Tissue Adhesion and Repair.

ABSTRACT: As life expectancy continues to increase, the inevitable weakening and rupture of bone tissue have grown as concerns in the medical community, thus leading to the need for adhesive materials suitable for bone repair applications. However, current commercially available adhesives face certain drawbacks that prevent proper tissue repair, such as low biocompatibility, poor adhesion to wet surfaces, and the need for high polymerization temperatures. This work aims to develop an injectable and photo-responsive chitosan methacrylate/graphene oxide (ChiMA/GO) adhesive nanocomposite hydrogel of high biocompatibility that is easy to apply by simple extrusion and that offers the possibility for in situ polymer and physiological temperatures. The nanocomposite was thoroughly characterized spectroscopically, microscopically, rheologically, thermally, and through mechanical, textural, and biological assays to fully evaluate its correct synthesis and functionalization and its performance under physiological conditions that mimic those observed in vivo. In addition, a finite element analysis (FEA) simulation was used to evaluate its performance in femur fractures. Results suggest the material's potential as a bioadhesive, as it can polymerize at room temperature, shows superior stability in physiological media, and is capable of withstanding loads from body weight and movement. Moreover, the material showed remarkable biocompatibility as evidenced by low hemolytic and intermediate platelet aggregation tendencies, and high cytocompatibility when in contact with osteoblasts. The comprehensive studies presented here strongly suggest that the developed hydrogels are promising alternatives to conventional bone adhesives that might be further tested in vivo in the near future.

SUBMITTER: Cespedes-Valenzuela DN

PROVIDER: S-EPMC8747203 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

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Preparation and Characterization of an Injectable and Photo-Responsive Chitosan Methacrylate/Graphene Oxide Hydrogel: Potential Applications in Bone Tissue Adhesion and Repair.

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