Injectable, antibacterial, and oxygen-releasing chitosan-based hydrogel for multimodal healing of bacteria-infected wounds.

Bacterial infection is one of the main challenges of wound healing. It imposes financial and healthcare costs. The emergence of antibiotic-resistant bacteria has increased concerns about this challenge, and made finding alternative solutions a crucial aim. We created a new, antibacterial, multifunctional hydrogel with synergistic chemodynamic and photothermal features for wound-healing applications. We fabricated a chitosan (CT)-based hydrogel containing tannic acid (TA), Fe, and MnO2 nanosheets (CT-TA-Fe-MnO2) via a simple method and characterized it. The antibacterial features (resulting from the production of reactive oxygen species within bacterial cells) and healing ability (via anti-inflammatory and hemostatic features) of the hydrogel were confirmed in vitro. In vivo results revealed the effectiveness of the CT-TA-Fe-MnO2 hydrogel in decreasing the hemostatic time, improving anti-inflammatory effects, and promoting wound healing during 14 days by enhancing the deposition and maturation of collagen fibers without affecting the vital organs. The fabricated CT-TA-Fe-MnO2 hydrogel could be a promising candidate with antibacterial and anti-inflammatory activities suitable for wound-healing applications.

Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues.

Driven by regulatory authorities and the ever-growing demands from industry, various artificial tissue models have been developed. Nevertheless, there is no model to date that is capable of mimicking the biomechanical properties of the skin whilst exhibiting the hydrophilicity/hydrophobicity properties of the skin layers. As a proof-of-concept study, tissue surrogates based on gel and silicone are fabricated for the evaluation of microneedle penetration, drug diffusion, photothermal activity, and ultrasound bioimaging. The silicone layer aims to imitate the stratum corneum while the gel layer aims to mimic the water-rich viable epidermis and dermis present in in vivo tissues. The diffusion of drugs across the tissue model is assessed, and the results reveal that the proposed tissue model shows similar behavior to a cancerous kidney. In place of typical in vitro aqueous solutions, this model can also be employed for evaluating the photoactivity of photothermal agents since the tissue model shows a similar heating profile to skin of mice when irradiated with near-infrared laser. In addition, the designed tissue model exhibits promising results for biomedical applications in optical coherence tomography and ultrasound imaging. Such a tissue model paves the way to reduce the use of animals testing in research whilst obviating ethical concerns.

Injectable Antibacterial Gelatin-Based Hydrogel Incorporated with Two-Dimensional Nanosheets for Multimodal Healing of Bacteria-Infected Wounds.

The design and development of multifunctional injectable hydrogels with high photothermal antibacterial activity and shape adaptability to accelerate bacteria-infected wound healing is of critical importance in clinical applications. In this study, a hybrid hydrogel composed of gelatin, iron, and MnO2 nanosheets was prepared by multiple interactions, including coordinative and hydrogen bonding as well as electrostatic attraction. The introduced MnO2 and Fe components made the hydrogels photothermally and chemodynamically active, thereby endowing them with potent antibacterial capabilities against both Gram-negative and Gram-positive bacteria. Because of the Fenton activity of the hydrogels, they could produce abandoned oxygen, which is highly crucial in the healing process of wounds. They also showed good cytocompatibility and hemocompatibility as well as high hemostatic properties. Moreover, the injectable hydrogels could fill irregular wounds and significantly accelerate bacteria-infected wound healing through decreasing the inflammatory response and increasing blood vessels. These features indicated the promising potential of the multifunctional hydrogel for healing infected full-thickness wounds.

Multifunctional Photoactive Hydrogels for Wound Healing Acceleration.

Light is an attractive tool that has a profound impact on modern medicine. Particularly, light-based photothermal therapy (PTT) and photodynamic therapy (PDT) show great application prospects in the prevention of wound infection and promoting wound healing. In addition, hydrogels have shown attractive advantages in the field of wound dressings due to their excellent biochemical effects. Therefore, multifunctional photoresponsive hydrogels (MPRHs) that integrate the advantages of light and hydrogels are increasingly used in biomedicine, especially in the field of wound repair. However, a comprehensive review of MPRHs for wound regeneration is still lacking. This review first focuses on various types of MPRHs prepared by diverse photosensitizers, photothermal agents (PHTAs) including transition metal sulfide/oxides nanomaterials, metal nanostructure-based PHTAs, carbon-based PHTAs, conjugated polymer or complex-based PHTAs, and/or photodynamic agents (PHDAs) such as ZnO-based, black-phosphorus-based, TiO2-based, and small organic molecule-based PHDAs. We also then discuss how PTT, PDT, and photothermal/photodynamic synergistic therapy can modulate the microenvironments of bacteria to inhibit infection. Overall, multifunctional hydrogels with both therapeutic and tissue regeneration capabilities have been discussed and existing challenges, as well as future research directions in the field of MPRHs and their application in wound management are argued.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated Fe3O4 (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.

Gas chromatographic detection of some nitro explosive compounds in soil samples after solid-phase microextraction with carbon ceramic copper nanoparticle fibers.

In this research, a new solid-phase microextraction fiber based on carbon ceramic composites with copper nanoparticles followed by gas chromatography with flame ionization detection was applied for the extraction and determination of some nitro explosive compounds in soil samples. The proposed method provides an overview of trends related to synthesis of solid-phase microextraction sorbents and their applications in preconcentration and determination of nitro explosives. The sorbents were prepared by mixing of copper nanoparticles with a ceramic composite produced by mixture of methyltrimethoxysilane, graphite, methanol, and hydrochloric acid. The prepared sorbents were coated on copper wires by dip-coating method. The prepared nanocomposites were evaluated statistically and provided better limits of detection than the pure carbon ceramic. The limit of detection of the proposed method was 0.6 µg/g with a linear response over the concentration range of 2-160 µg/g and square of correlation coefficient >0.992. The new proposed fiber has been demonstrated to be a suitable, inexpensive, and sensitive candidate for extraction of nitro explosive compounds in contaminated soil samples. The constructed fiber can be used more than 100 times without the need for surface generation.