Infection-responsive long-term antibacterial bone plates for open fracture therapy.

The infections in open fracture induce high morbidity worldwide. Thus, developing efficient anti-infective orthopedic devices is of great significance. In this work, we designed a kind of infection-responsive long-term antibacterial bone plates. Through a facile and flexible volatilization method, a multi-aldehyde polysaccharide derivative, oxidized sodium alginate, was crosslinked with multi-amino compounds, gentamycin and gelatin, to fabricate a uniform coating on Ti bone plates via Schiff base reaction, which was followed by a secondary crosslinking process by glutaraldehyde. The double-crosslinked coating was stable under normal condition, and could responsively release gentamycin by the triggering of the acidic microenvironment caused by bacterial metabolism, owning to the pH-responsiveness of imine structure. The thickness of the coating was ranging from 22.0 µm to 63.6 µm. The coated bone plates (Ti-GOGs) showed infection-triggered antibacterial properties (>99%) and high biocompatibility. After being soaked for five months, it still possessed efficient antibacterial ability, showing its sustainable antibacterial performance. The in vivo anti-infection ability was demonstrated by an animal model of infection after fracture fixation (IAFF). At the early stage of IAFF, Ti-GOGs could inhibit the bacterial infection (>99%). Subsequently, Ti-GOGs could promote recovery of fracture of IAFF. This work provides a convenient and universal strategy for fabrication of various antibacterial orthopedic devices, which is promising to prevent and treat IAFF.

Derma-like antibacterial polysaccharide gel dressings for wound care.

Large skin wound infections have high morbidity, which threaten the health of human beings severely. It is essential to develop new wound dressings that can block microbial invasion, eliminate bacteria effectively, adhere to wounds firmly, and have good biocompatibility. In this work, we designed a kind of polysaccharide gel (DLG) dressings with derma-like structure that had good wound care performances. With a facile penetration cross-linking method by the Schiff base reaction between oxidized hyaluronic acid solution and carboxymethyl chitosan solution with higher viscosity, a gradient porous structure was formed inside DLG to mimic the structure of derma, which was due to the simultaneous penetration and reaction processes between two viscous solutions. This derma-like structure endowed the gel dressings with the abilities of self-adhesion to wounds and barriers against bacteria. Through the introduction of cuttlefish juice and gentamycin, the modified gel dressings (DLG-GS) showed mild photothermal effects under the near infrared irradiation at the wavelength of 808 nm, which could reach and maintain the temperature of 45 °C. The mild heat could act together with gentamycin to produce a rapid bactericidal performance within 5 min. Meanwhile, the polysaccharide gel dressings had good biocompatibility. The in vivo anti-infection properties of DLG-GS was demonstrated by an animal model of infected full-thickness skin defect. This strategy provided a feasible solution for the prevention and treatment of infected large wounds. STATEMENT OF SIGNIFICANCE: Derma-like antibacterial gel dressings (DLG-GS) with high bacterial barrier ability, strong tissue adhesive property and good biocompatibility were constructed by a penetration cross-linking method. DLG-GS could eliminate bacterial infection within 5 min due to the rational combination of a mild photothermal effect and antibiotics. DLG-GS showed high anti-infection and wound healing properties in an animal model of infected full-thickness skin defect. This study provides a flexible and universal strategy for the development  of antibacterial wound dressings.

Effects of Bunao-Fuyuan decoction serum on proliferation and migration of vascular smooth muscle cells in atherosclerotic.

Atherosclerosis (AS) is a chronic inflammatory disease, the main causes of which include abnormal lipid metabolism, endothelial injury, physical and chemical injury, hemodynamic injury, genetic factors and so on. These causes can lead to inflammatory injury of blood vessels and local dysfunction. Bunao-Fuyuan decoction (BNFY) is a traditional Chinese medicine compound that can treat cardiovascular and cerebrovascular diseases, but its effect on AS is still unknown. The aim of this study was to investigate the effect and mechanism of BNFY in proliferation and migration of vascular smooth muscle cells (VSMCs) on AS. At first, the expression of α-SMA protein in ox-LDL-induced VSMCs, which was detected by immunofluorescence staining and western blot. CCK-8 technique and cloning technique were used to detect the cell proliferation of ox-LDL-induced VSMCs after adding BNFY. Meanwhile, the expression of proliferating protein Ki67 was detected by immunofluorescence staining. Western blot was also used to detect the expression of proliferation-related proteins CDK2, CyclinE1 and P27. Flow cytometry was used to detect the effect of BNFY on cell cycle. The effects of BNFY on proliferation and migration of cells were detected by cell scratch test and Transwell. Western blot was used to detect the expression of adhesion factors ICAM1, VCAM1, muc1, VE-cadherin and RHOA/ROCK-related proteins in cells. We found that the expression of AS marker α-SMA protein increased significantly and cells shriveled and a few floated on the medium after induction of ox-LDL on VSCMs. The proliferation rate of ox-LDL VSMCs decreased significantly after adding different doses of BNFY, and BNFY can inhibit cell cycle. Meanwhile, we also found that cell invasion and migration rate were significantly inhibited and related cell adhesion factors ICAM1, VCAM1, muc1 and VE-cadherin were inhibited too by BNFY. Finally, we found that BNFY inhibited the expression of RHOA, ROCK1, ROCK2, p-MLC proteins in the RHOA/ROCK signaling pathway. Therefore, we can summarize that BNFY may inhibit the proliferation and migration of atherosclerotic vascular smooth muscle cells by inhibiting the activity of RHOA/ROCK signaling pathway.