Prevention of bacterial infection and reduction of hemorrhage, the primary challenges posed by trauma before hospitalization, are essential steps in prolonging the patient's life until they have been transported to a trauma center. Extracellular matrix (ECM) hydrogel is a promising biocompatible material for accelerating wound closure. However, due to the lack of antibacterial properties, this hydrogel is difficult to be applied to acute contaminated wounds. This study formulates an injectable dermal extracellular matrix hydrogel (porcine acellular dermal matrix (ADM)) as a scaffold for skin defect repair. The hydrogel combines vancomycin, an antimicrobial agent for inducing hemostasis, expediting antimicrobial activity, and promoting tissue repair. The hydrogel possesses a porous structure beneficial for the adsorption of vancomycin. The antimicrobial agent can be timely released from the hydrogel within an hour, which is less than the time taken by bacteria to infest an injury, with a cumulative release rate of approximately 80%, and thus enables a relatively fast bactericidal effect. The cytotoxicity investigation demonstrates the biocompatibility of the ADM hydrogel. Dynamic coagulation experiments reveal accelerated blood coagulation by the hydrogel. In vivo antibacterial and hemostatic experiments on a rat model indicate the healing of infected tissue and effective control of hemorrhaging by the hydrogel. Therefore, the vancomycin-loaded ADM hydrogel will be a viable biomaterial for controlling hemorrhage and preventing bacterial infections in trauma patients.
Background Hydrogels loaded with antimicrobial agents have been widely used for treating infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of an AgNP-impregnated PADM (AgNP–PADM) hydrogel on the treatment of infected wounds. Methods An AgNP–PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of the PADM and AgNP–PADM hydrogels to treat infected wounds in animals. Results The PADM and AgNP–PADM hydrogels were pH sensitive, which made them flow dynamically and solidify under acidic and neutral conditions, respectively. The hydrogels also exhibited porous network structures, satisfactory moisture retention, and slow degradation. Additionally, the AgNP–PADM hydrogel showed a slow and sustained release of AgNPs for at least 7 days without the particle size changing. Thus, the AgNPs exhibited adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNP–PADM hydrogel promoted angiogenesis and healed infected skin defects in vivo. Conclusions The AgNP–PADM hydrogel is a promising bioderived antibacterial material for clinical application to infected wound dressings.
Gastric cancer (GC) is one of the most common malignant tumors in the world. GPx4, as the core regulator of ferroptosis, has become a potential molecular target for developing anticancer agents. In the present study, we found that GPx4 was overexpressed and negatively correlated with poor prognosis in GC, while it was associated with the GC development. Molecular docking and structure-based virtual screening assays were used to screen potential GPx4 inhibitors, and we identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in GC cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cells in vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe 2+ by transporting Fe 3+ into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. In addition, PB can also suppresses tumor growth in an orthotopic mouse model of GC via regulating the expression of GPx4, TFR1, NOCA4 and FTH1 in vivo. In summary, we confirmed that GPx4 may be a potential target for GC treatment, PB may be a novel and promising drug for the treatment of GC, which shows good antitumor efficacy without causing significant host toxicity via inducing ferroptosis in both gastric cancer cells and mouse models.
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