Molecular-scale insights into confined clindamycin in nanoscale pores of mesoporous silica.

Clindamycin is an antibiotic used to treat a variety of bacterial infections. The sustained release of clindamycin from the drug carrier is an important strategy to prolong the effective antibacterial duration. In this work, the microstructure and dynamics of clindamycin confined into the nanopores of mesopore silica with different pore sizes were studied using molecular dynamics simulation. It is found that there is a layering behavior for clindamycin distribution as a function of distance from the pore surface to the pore center with preferred location near the surface of the nanopore. The radial distribution function between carbonyl oxygen and the silanol groups shows the highest intensity of the first peak with the preferred orientation of carbonyl oxygen pointing toward the pore surface, which suggests the strong interaction between the carbonyl oxygen and the silanol groups on the pore surface. The higher local diffusion coefficients for the clindamycin molecules near the pore surface can be found. In addition, the presence of water can lead to the shift of clindamycin distribution away from the surface and promote the local diffusion of clindamycin near the pore surface. The information in this work will provide the microscopic understanding for the design of the drug carriers for the controlled release of clindamycin.

Balancing the antibacterial and osteogenic effects of double-layer TiO2 nanotubes loaded with silver nanoparticles for the osseointegration of implants.

The improvement of Ag nanoparticles (AgNPs), in particular, loaded titania nanotubes, includes not only the antibacterial effect but also balancing the side effects from the antibacterial effect and osteogenesis properties, which can lead to an increased success rate of implants. Herein, based on the various needs of the graft to inhibit bacteria at different stages in vivo, we used a special osteogenic honeycomb-like "large tube over small tube" double-layered nanotube structure and created ultra-small-sized silver nanoparticles uniformly loaded on the surface and the interior of double-layer nanotubes by an optimized sputter coating method to ensure the time-dependent controllable release of antibacterial Ag ions from grafts and achieve the balance of the antibacterial effect and osteogenesis properties. The release of Ag+ from DNT-Ag8 was determined by inductively coupled plasma spectrometry. The release rate of Ag was slow; it was 30% on the first day and plateaued by the 19th day. Porphyromonas gingivalis adhesion and live bacteria were less abundant on the surface of DNT-Ag8, reaching an antibacterial efficiency of 55.6% in vitro. DNT-Ag8 shows a significantly higher antibacterial effect in a rat model infected with Staphylococcus aureus. An in vitro study demonstrated that DNT-Ag8 had no adverse effects on the adhesion, viability, proliferation, ALP staining, or activity assays of rat BMSCs. In contrast, it increased the expression of osteogenic genes. In vivo, DNT-Ag8 promoted bone-implant osseointegration in a beagle mandibular tooth loss model. This study demonstrated that the uniform loading of small-diameter silver nanoparticles using a honeycomb bilayer nanotube template structure is a promising method for modifying titanium surfaces to improve both bacteriostasis and osseointegration.

Titanium Nanobowl-Based Nest-Like Nanofiber Structure Prepared at Room Temperature and Pressure Promotes Osseointegration of Beagle Implants.

Nest-like nanofiber structures have potential applications in surface modifications of titanium implants. In this study, nest-like nanofiber structures were prepared on a titanium surface at room temperature and pressure by using the nanobowl template-assisted method combined with alkali etching. The characterization and biocompatibility of this material were analyzed by cellular adhesion, death, CCK-8, ALP, and RT-PCR assays in vitro, and osseointegration was evaluated by micro-CT and fluorescent labeling in vivo. The results showed that this nest-like nanofiber structure has a firmer and asperate surface than nanotubes, which leads to better cellular adhesion, proliferation, and differentiation capacity. In a beagle alveolar bone implant model, the nest-like nanofiber structure showed a better osseointegration capacity. In conclusion, this nest-like nanofiber structure has potential applications in dental implantology.

[Accuracy of implantation between two immediate implantation methods in mandibular molars].

PURPOSE: To compare the accuracy of implant placement between modified and traditional immediate implant placement in mandibular molar regions. METHODS: Twenty-four patients were selected for immediate implantation in the molar area including 24 implantation sites. Preoperative cone-beam CT(CBCT) was conducted and then digital software Simplant 18.0 was used to design the ideal three-dimensional position of the implants. In the experimental group, the implant socket was prepared first according to reference of the remaining natural teeth, then the implant was implanted after minimally invasive extraction. Twelve patients in the control group underwent immediate implantation by traditional immediate implant procedures. Minimally invasive extraction, then socket preparation, and final implanting were performed. All patients underwent CBCT after surgery. Implant sites designed prior to surgery and actual implant sites differences between modified and traditional immediate implant placement were measured by Simplant 18.0 and compared with SPSS 17.0 software package. RESULTS: In the experimental group and control group, the measured average deviation were as follows, the angle was (4.492±0.912)° and (7.255±1.307)°, respectively; The horizontal error of the implant shoulder was (0.379±0.083) mm and (1.229±0.270) mm, respectively; The measuring horizontal error of the implant apex was (1.263±0.267) mm and (2.183±0.264) mm, respectively; The calculative horizontal error of the implant apex was (1.324±0.203) mm and (2.709±0.383) mm, respectively; Depth error of the implant apex was (0.663±0.123) mm and (1.533±0.155) mm, respectively, which were significantly lower than those of the control group. CONCLUSIONS: Compared with the traditional method, modified immediate implantation can improve the accuracy of implantation in mandibular molars.

Sequential release of immunomodulatory cytokines binding on nano-hydroxyapatite coated titanium surface for regulating macrophage polarization and bone regeneration.

Inflammation occurs when the material is implanted into the body. As one of the important immune cells in the regulation of inflammation, macrophages are able to remove pathogens and necrotic cells, and polarize to different phenotypes to regulate inflammatory response for tissue regeneration. Therefore, it is known that the sequential release of immunomodulatory cytokines from the surface of titanium (Ti) implants can regulate the polarization of macrophages and promote osseointegration of implants. In order to control the switch of macrophage phenotypes at desired time, we fabricated hydroxyapatite (HAp) nanotube arrays coating on Ti surface, by acid-etching, alkali-heating and HAp coating sequentially. Then we loaded the interleukin-4 (IL-4) encapsulated by poly (lactic-co-glycolic acid) (PLGA) on the bottom of the nanotube and the interferon-γ (IFN-γ) encapsulated by sodium hyaluronate (SH) on the top of the nanotube. Based on the physical and chemical properties of PLGA and SH and the spatial distribution of loaded cytokines, we hypothesized that the programmed release of IFN-γ and IL-4, which made the phenotypic transition of macrophages at a specific time, so as to regulate inflammation and promote osteogenic repair. Our hypothesis created a new type of drug sustained release system, which has high research value for improving the osseointegration of implants.

[Mechanical properties of 3D-printed titanium mesh and its biocompatibility in vitro].

PURPOSE: To compare the mechanical properties of 3D-printed titanium meshes and pre-shaped titanium meshes, and to evaluate the effects of 3D-printed titanium meshes on cell proliferation and differentiation. METHODS: 3D- printed titanium meshes were produced and prepared with laser printing machine. The mechanical properties were analyzed by static tension and compression load test. Bone marrow mesenchymal stem cells (BMSCs) were extracted from 4-week-old male SD rats. BMSCs were co-cultured with 3D-printed titanium meshes of different apertures. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Alkaline phosphatase (ALP) activity assay was used to test ALP activity. The expression of related osteogenic genes was tested by real-time PCR. The adhesion and growth of BMSCs were investigated by scanning electron microscopy (SEM) and living / dead cell staining. SPSS 22.0 software package was used for statistical analysis of the results. RESULTS: The results of 3D-printing Ti-meshes tension and compression loading experiment were excellent. The 3D-printing Ti-meshes showed no inhibitory effects on cell proliferation, survival and adhesion, but had a positive effect on osteogenesis of BMSCs. CONCLUSIONS: The mechanical properties of 3D-printed Ti-meshes are excellent. The 3D-printed Ti-meshes have good biocompatibility.