Multifunctional nanocarriers for the treatment of periodontitis: Immunomodulatory, antimicrobial, and regenerative strategies.

Periodontitis is an inflammatory disease, in which the host immuno-inflammatory response against the dysbiotic subgingival biofilm leads to the breakdown of periodontal tissues. Most of the available treatments seem to be effective in the short-term; nevertheless, permanent periodical controls and patient compliance compromise long-term success. Different strategies have been proposed for the modulation of the host immune response as potential therapeutic tools to take a better care of most susceptible periodontitis patients, such as drug local delivery approaches. Though, maintaining an effective drug concentration for a prolonged period of time has not been achieved yet. In this context, advanced drug delivery strategies using biodegradable nanocarriers have been proposed to avoid toxicity and frequency-related problems of treatment. The versatility of distinct nanocarriers allows the improvement of their loading and release capabilities and could be potentially used for microbiological control, periodontal regeneration, and/or immunomodulation. In the present review, we revise and discuss the most frequent biodegradable nanocarrier strategies proposed for the treatment of periodontitis, including polylactic-co-glycolic acid (PLGA), chitosan, and silica-derived nanoparticles, and further suggest novel therapeutic strategies.

Development of novel antimicrobial acrylic denture modified with copper nanoparticles.

PURPOSE: This study aimed to synthesize heat-cured poly(methyl methacrylate) (PMMA) acrylic formulated with copper nanoparticles (nCu) for producing dentures with antimicrobial properties and ability to prevent denture stomatitis (DS). METHODS: nCu/PMMA nanocomposites were prepared through in situ formation of nCu into methyl methacrylate (MMA). The fabricated material was characterized using scanning electron microscopy, spectroscopy (energy-dispersive X-ray, attenuated total reflectance-Fourier-transform infrared, and X-ray photoelectron spectroscopy), X-ray diffraction analysis, and mechanical flexural tests (ISO 20795-1:2008). Antimicrobial activity against Candida albicans and oral bacteria was determined. MTS assay (ISO 10993-5:2009) and copper release experiments were conducted to assess cytotoxicity. In the clinical trial, participants wearing nCu/PMMA (n=25) and PMMA (n=25) dentures were compared; specifically, DS incidence and severity and Candida species proliferation were assessed for 12 months. Data were analyzed using analysis of variance with Tukey's post hoc test (α=0.05). RESULTS: nCu/PMMA nanocomposite loaded with 0.045% nCu exhibited the maximum antimicrobial activity against C. albicans and other oral bacteria without producing cytotoxicity in the wearer. nCu/PMMA dentures retained their mechanical and aesthetic properties as well as inhibited the growth of Candida species on both denture surface and patient palate. DS incidence and severity were lower in the nCu/PMMA denture group than in the PMMA denture group. CONCLUSIONS: PMMA acrylic produced with copper nanotechnology is antimicrobial, biocompatible, and aesthetic and can reduce DS incidence. Thus, this material may act as a novel preventive alternative for oral infections associated with denture use.

Nanoparticles of Bioactive Glass Enhance Biodentine Bioactivity on Dental Pulp Stem Cells.

This study aimed to investigate the cytotoxicity and bioactivity of a novel nanocomposite containing nanoparticles of bioactive glass (nBGs) on human dental pulp stem cells (hDPSCs). nBGs were synthesized by the sol-gel method. Biodentine (BD) nanocomposites (nBG/BD) were prepared with 2 and 5% wt of nBG content; unmodified BD and glass ionomer cement were used as references. Cell viability and attachment were evaluated after 3, 7 and 14 days. Odontogenic differentiation was assessed with alkaline phosphatase (ALP) activity after 7 and 14 days of exposure. Cells successfully adhered and proliferated on nBG/BD nanocomposites, cell viability of nanocomposites was comparable with unmodified BD and higher than GIC. nBG/BD nanocomposites were, particularly, more active to promote odontogenic differentiation, expressed as higher ALP activity of hDPSCs after 7 days of exposure, than neat BD or GIC. This novel nanocomposite biomaterial, nBG/BD, allowed hDPSC attachment and proliferation and increased the expression of ALP, upregulated in mineral-producing cells. These findings open opportunities to use nBG/BD in vital pulp therapies.

Preparation and osteogenic properties of nanocomposite hydrogel beads loaded with nanometric bioactive glass particles.

Bone reconstruction in the oral and maxillofacial region presents particular challenges related to the development of biomaterials with osteoinductive properties and suitable physical characteristics for their surgical use in irregular bony defects. In this work, the preparation and bioactivity of chitosan-gelatin (ChG) hydrogel beads loaded with either bioactive glass nanoparticles (nBG) or mesoporous bioactive glass nanospheres (nMBG) were studied.In vitrotesting of the bionanocomposite beads was carried out in simulated body fluid, and through viability and osteogenic differentiation assays using dental pulp stem cells (DPSCs).In vivobone regenerative properties of the biomaterials were assessed using a rat femoral defect model and compared with a traditional maxillary allograft (Puros®). ChG hydrogel beads containing homogeneously distributed BG nanoparticles promoted rapid bone-like apatite mineralization and induced the osteogenic differentiation of DPSCsin vitro. The bionanocomposite beads loaded with either nBG or nMBG also produced a greater bone tissue formationin vivoas compared to Puros® after 8 weeks of implantation. The osteoinductivity capacity of the bionanocomposite hydrogel beads coupled with their physical properties make them promissory for the reconstruction of irregular and less accessible maxillary bone defects.

In situ preparation and osteogenic properties of bionanocomposite scaffolds based on aliphatic polyurethane and bioactive glass nanoparticles.

Bionanocomposite scaffolds based on aliphatic polyurethane (PU) and bioactive glass nanoparticles were produced by using a one-step in situ polymerization method. Bioactive glass nanoparticles (nBG) or mesoporous BG nanospheres (nMBG) were incorporated during the polymerization reaction to produce simultaneous formation and foaming of porous nanocomposite scaffolds. The in vitro bioactivity of the scaffolds was assessed in simulated body fluid (SBF), and through cytocompatibility and osteogenic differentiation assays with stem cells. Bone regeneration properties of the scaffold materials were in vivo assessed by using a critical-sized femoral defect model in rat. The scaffold nanocomposites showed excellent cytocompatibility and ability to accelerate the crystallization of bone-like apatite in vitro. nBG/PU bionanocomposite scaffold exhibited the higher capacity to stimulate osteogenic cell differentiation as judged by an increased ALP activity and the presence of mineralized nodules associated with the stem cells. nBG (5%)/PU scaffold significantly also produces in vivo a denser and more significant amount of new bone after 8 weeks of implantation, which is attributed to the more rapid dissolution rate of nBG into osteogenic ionic products compared to nMBG. The results of this work show that the in situ polymerization method combined with the use of nanodimensional BG particles enable the production of PU - based scaffolds with enhanced bioactive properties to stimulate the bone tissue regeneration.

Bionanocomposite scaffolds based on chitosan-gelatin and nanodimensional bioactive glass particles: In vitro properties and in vivo bone regeneration.

Bone repair bionanocomposite scaffolds were produced by incorporating dense bioactive glass nanoparticles or mesoporous bioactive glass nanospheres into a chitosan-gelatin polymer blend. The in vitro bioactivity of the scaffolds was assessed in simulated body fluid, and cell viability and osteogenic differentiation assays were performed with dental pulp stem cells. Bone regeneration properties of the scaffold materials were in vivo assessed by using a critical-sized femoral defect model in rat. The scaffold nanocomposites showed excellent cytocompatibility and ability to accelerate the crystallization of bone-like apatite in vitro. Bionanocomposites prepared with bioactive glass nanoparticles were particularly more active to promote the osteogenic differentiation of dental pulp stem cells as judged by the higher activity of alkaline phosphatase. This result is attributed to the faster dissolution of bioactive glass nanoparticles into osteogenic ionic products compared to mesoporous bioactive glass nanospheres. In vivo experiments demonstrated that bioactive glass nanoparticles (5%)/chitosan-gelatin bionanocomposite significantly produces the highest amount of new bone (∼80%) in the defect area after eight weeks of implantation. The bone regeneration capacity exhibited by the scaffolds formulated with nanodimensional bioactive glass particles make them attractive for bone reconstruction applications.

A comparative study on the microstructural and antibacterial properties of Laser - textured and SLA dental implants

ABSTRACT: Objective: To compare the structural and antibacterial properties of a Laser - treated commercial dental implant (No-Itis®) with those of a traditional sandblasted and acid-etched (SLA) implant. Materials and Methods: Surface topography and elemental composition of the implant surfaces were analyzed by using scanning electron microscopy (SEM) coupled to dispersive X - ray spectrometry (EDX). The antibacterial properties of the implants were tested against Aggregatibacter actinomycetemcomitans. Protein adsorption capacity and bioactivity in simulated body fluid (SBF) of the implant surfaces were also analyzed. Results: The Laser - treated implant presents a topography constituted by smooth and uniform concavities of ~ 30 µm in diameter, free of Laser - induced alterations, and impurity elements. The Laser - textured surface demonstrated to significantly (p = 0.0132) reduce by up to around 61% the bacterial growth as compared with the SLA implant, which was found to be associated to a reduced adhesion of proteins on the Laser surface. No apatite - related mineral deposits were detected on the SBF - incubated surfaces. Conclusion: The smooth Laser - designed surface exhibits an antimicrobial effect that decreases the growth of bacterial biofilm on its surface, which could contribute to reduce the risk of peri-implantitis.

Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015.