Extracorporeal magnetic approach to reduce the unwanted side-effects and improve antibacterial activity of Ag/Fe3 O4 nanocomposites in rat.

While Ag nanoparticles hold great promise for broad spectrum antibacterial activity, the potential risks of Ag nanoparticles (NPs) on human health remain a challenge. In this study, Ag/Fe3 O4 composites have been successfully prepared and characterized by transmission electron microscopy, X-ray powder diffraction, and Fourier-transform infrared spectroscopy, and their magnetic and antibacterial properties have been assessed. In vivo results show that the antibacterial effect of 500 µg/mL Ag/Fe3 O4 nanocomposites was significantly higher than that of 1000 µg/mL AgNPs after 72 h of treatment (p < 0.01). Hematoxylin and eosin (HE) staining showed that squamous epithelium and dermis collagen fibers formed in the Ag/Fe3 O4 group after 8 days treatment. Wound closure was significantly better for the Ag/Fe3 O4 group than for the AgNPs group. On the other hand, there was less Ag in blood, liver, and kidney in the Ag/Fe3 O4 group, as more Ag was retained in the wound. According to lactate dehydrogenase, γ-glutamyl transpeptidase, and reactive oxygen species results, Ag/Fe3 O4 nanocomposites caused less unwanted side-effects. This work presents a new paradigm to reduce the unwanted side-effects of AgNPs and improve their antibacterial activity, providing a new avenue for wound healing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2029-2036, 2018.

Evaluation of a two-stage antibacterial hydrogel dressing for healing in an infected diabetic wound.

Various types of wound dressings have been used to treat complex infections in diabetes mellitus. This study is the first to evaluate the healing effects using a two-stage dressing in infected diabetic wounds. A two-stage antibacterial hydrogel dressing (two-stage dressing) was established with two time phases, an antibacterial phase and a drug release phase. We established each phase by using a swelling and rate of drug release test. These results suggested that the antimicrobial phase is activated as soon as the two-stage dressing attaches to the skin. The drugs in the drug release layer of the dressing were released to a greater extent than expected 20-36 h after attachment to the skin, likely due to extensive water absorption. Histological analysis and measurement of vascular endothelial growth factor expression through in vivo testing suggested that the benefits of a two-stage dressing include rapid antibacterial properties, sustained drug release, and promotion of wound healing through cell proliferation as compared with the traditional composite antibacterial hydrogel dressing. Further in vivo tests confirmed that separation of the antibacterial and drug-releasing properties, along with biocompatibility and rapid wound closure rates made two-stage dressings suitable for healing of infected wounds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1808-1817, 2017.

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

OBJECTIVES: Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. METHODS: The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. RESULTS: The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. CONCLUSIONS: Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.

Effect of "phase change" complex on postoperative adhesion prevention.

BACKGROUND: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). MATERIALS AND METHODS: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. RESULTS: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery. CONCLUSIONS: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

Comparative Study of Biosafety, DNA, and Chromosome Damage of Different-Materials-Modified Fe3O4 in Rats.

The increasing use of modified Fe3O4 magnetic microparticles has raised safety concerns regarding their use and effect on human health. This study assessed the in vivo biosafety, DNA, and chromosome damage of modified Fe3O4 microparticles such as Au@Fe3O4, Ag@Fe3O4, Cs@Fe3O4, Pt@Fe3O4, and CdS@Fe3O4, using spleen-deficient rats. Spleen-deficient rats treated with naked and modified (Au, Cs, Pt) Fe3O4 microparticles (5000 mg/kg) displayed low toxicity. Only treatment with Cds@Fe3O4 resulted in elevated toxicity and death in rats. Au-, Ag-, and Pt-modified Fe3O4 increased the rate of hemolysis in rats relative to treatment with naked Fe3O4. Despite this, Au- and Pt-modified Fe3O4 increased the biocompatibility and reduced DNA and chromosome damage in rats relative to naked Fe3O4. While Cs@Fe3O4 microparticles displayed a higher biocompatibility than naked Fe3O4, they displayed no significant reduction in DNA and chromosome damage. In summary, Au and Pt surface-modified Fe3O4 microparticles display elevated in vivo biosafety compared to unmodified particles. The precious metal material, with good biological compatibility, surface modification of Fe3O4 is an effective strategy to improve the overall safety and potential therapeutic utility of these magnetic materials.

Influence of reducing agents on biosafety and biocompatibility of gold nanoparticles.

Extensive biomedical applications of nanoparticles are mainly determined by their safety and compatibility in biological systems. The aim of this study was to compare the biosafety and biocompatibility of gold nanoparticles (GNPs) prepared with HEPES buffer, which is popular for cell culture, and sodium citrate, a frequent reducing agent. From experimental results on the body weight and organ coefficients of acute oral toxicity tests, it could be observed that HEPES-prepared GNPs are biologically safer than citric-prepared GNPs at the same dose of 500 µg/kg. The in vitro cell viability was higher for HEPES-prepared GNPs than citric-prepared GNPs at 5.0- and 10.0-ug/mL concentrations. More reactive oxygen species (ROS) were generated in the cell suspension when supplemented with citric-prepared GNPs than HEPES-prepared GNPs when their concentrations were higher than 20 µg/mL. The results stated that HEPES-prepared GNPs had better biosafety and biocompatibility than citric-prepared GNPs. This study not only revealed the influence of reducing agent on biosafety and biocompatibility of nanomaterials but also provided accumulative evidence for nanomaterials in biomedical applications.