Novel chlorhexidine-loaded polymeric nanoparticles for root canal treatment

Persistence of microorganisms in dentinal tubules after root canal chemo-mechanical preparation has been well documented. The complex anatomy of the root canal and dentinal buffering ability make delivery of antimicrobial agents difficult. This work explores the use of a novel trilayered nanoparticle (TNP) drug delivery system that encapsulates chlorhexidine digluconate, which is aimed at improving the disinfection of the root canal system. Chlorhexidine digluconate was encapsulated inside polymeric self-assembled TNPs. These were self-assembled through water-in-oil emulsion from poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), a di-block copolymer, with one hydrophilic segment and another hydrophobic. The resulting TNPs were physicochemically characterized and their antimicrobial effectiveness was evaluated against Enterococcus faecalis using a broth inhibition method. The hydrophilic interior of the TNPs successfully entrapped chlorhexidine digluconate. The resulting TNPs had particle size ranging from 140–295 nm, with adequate encapsulation efficiency, and maintained inhibition of bacteria over 21 days. The delivery of antibacterial irrigants throughout the dentinal matrix by employing the TNP system described in this work may be an effective alternative to improve root canal disinfection

A Model Study to Evaluate Osseointegration and Fracture Healing Following Open Reduction and Internal Fixation (ORIF) in Diabetic Lewis Rats

There is a higher risk of implant osseointegration failure after open reduction and internal fixation (ORIF) in patients with diabetes due to increased inflammatory conditions, associated metallic corrosion and infection. While it is possible to avoid elective osseous surgery in patients with diabetes, it may not be the case in nonelective cases, such as ORIF ankle fractures. A total of 30 male Lewis rats (12-15 weeks old) were distributed into diabetic (D) and nondiabetic (ND) groups. Fracture healing and osseointegration were evaluated at 2-, 10-, and 21-day time points. Microtomographic and histological analysis depicted distinct differences in fracture healing and osseointegration between D and ND animals. Immunohistochemical analysis exhibited elevated proliferation (PCNA) and osteogenic (Runx2) cells for ND animals, while HMGB1 (inflammatory marker) was elevated for D animals during healing. Bone resorption marker CTX-1 was elevated in the plasma of D animals at 2 days, while bone formation marker P1NP was higher for ND animals at 10 days. Overall, this model resulted in delayed implant osseointegration and fracture healing in diabetic animals, highlighting the importance of developing new biomaterials or implant coatings that can improve bone healing outcomes in this patient population

Oral implant osseointegration model in C57Bl/6 mice: microtomographic, histological, histomorphometric and molecular characterization

Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field. Objective: In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice. Material and Methods: Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days). Results: The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers. Conclusions: This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis

HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice

The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome

Insatisfação com o corpo, auto estima e preocupação com o peso em escolares de 8 a 11 de Porto Alegre : estudo piloto

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From Data to Software to Science with the Rubin Observatory LSST

The Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) dataset will dramatically alter our understanding of the Universe, from the origins of the Solar System to the nature of dark matter and dark energy. Much of this research will depend on the existence of robust, tested, and scalable algorithms, software, and services. Identifying and developing such tools ahead of time has the potential to significantly accelerate the delivery of early science from LSST. Developing these collaboratively, and making them broadly available, can enable more inclusive and equitable collaboration on LSST science. To facilitate such opportunities, a community workshop entitled "From Data to Software to Science with the Rubin Observatory LSST" was organized by the LSST Interdisciplinary Network for Collaboration and Computing (LINCC) and partners, and held at the Flatiron Institute in New York, March 28-30th 2022. The workshop included over 50 in-person attendees invited from over 300 applications. It identified seven key software areas of need: (i) scalable cross-matching and distributed joining of catalogs, (ii) robust photometric redshift determination, (iii) software for determination of selection functions, (iv) frameworks for scalable time-series analyses, (v) services for image access and reprocessing at scale, (vi) object image access (cutouts) and analysis at scale, and (vii) scalable job execution systems. This white paper summarizes the discussions of this workshop. It considers the motivating science use cases, identified cross-cutting algorithms, software, and services, their high-level technical specifications, and the principles of inclusive collaborations needed to develop them. We provide it as a useful roadmap of needs, as well as to spur action and collaboration between groups and individuals looking to develop reusable software for early LSST science.Comment: White paper from "From Data to Software to Science with the Rubin Observatory LSST" worksho

From Data to Software to Science with the Rubin Observatory LSST

editorial reviewedThe Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) dataset will dramatically alter our understanding of the Universe, from the origins of the Solar System to the nature of dark matter and dark energy. Much of this research will depend on the existence of robust, tested, and scalable algorithms, software, and services. Identifying and developing such tools ahead of time has the potential to significantly accelerate the delivery of early science from LSST. Developing these collaboratively, and making them broadly available, can enable more inclusive and equitable collaboration on LSST science. To facilitate such opportunities, a community workshop entitled "From Data to Software to Science with the Rubin Observatory LSST" was organized by the LSST Interdisciplinary Network for Collaboration and Computing (LINCC) and partners, and held at the Flatiron Institute in New York, March 28-30th 2022. The workshop included over 50 in-person attendees invited from over 300 applications. It identified seven key software areas of need: (i) scalable cross-matching and distributed joining of catalogs, (ii) robust photometric redshift determination, (iii) software for determination of selection functions, (iv) frameworks for scalable time-series analyses, (v) services for image access and reprocessing at scale, (vi) object image access (cutouts) and analysis at scale, and (vii) scalable job execution systems. This white paper summarizes the discussions of this workshop. It considers the motivating science use cases, identified cross-cutting algorithms, software, and services, their high-level technical specifications, and the principles of inclusive collaborations needed to develop them. We provide it as a useful roadmap of needs, as well as to spur action and collaboration between groups and individuals looking to develop reusable software for early LSST science

Molecular-Level Understanding of the Influence of Ions and Water on HMGB1 Adsorption Induced by Surface Hydroxylation of Titanium Implants

Due to its excellent chemical and mechanical properties, titanium has become the material of choice for orthopedic and dental implants to promote rehabilitation via bone anchorage and osseointegration. Titanium osseointegration is partially related to its capability to form a TiO2 surface layer and its ability to interact with key endogenous proteins immediately upon implantation, establishing the first bone-biomaterial interface. Surgical trauma caused by implantation results in the release of High Mobility Group Box 1 (HMGB1) protein, which is a prototypic DAMP (Damage Associated Molecular Pattern) with multiple roles in inflammation and tissue healing. To develop different surface strategies that improve the clinical outcome of titanium-based implants by controlling their biological activity, a molecular-scale understanding of HMGB1-surface interactions is desired. Here, we use molecular dynamics (MD) computer simulations to provide direct insight into the HMGB1 interactions and the possible molecular arrangements of HMGB1 on fully hydroxylated and non-hydroxylated rutile (110) TiO2 surfaces. The results establish that HMGB1 is most likely to be adsorbed directly onto the surface regardless of surface hydroxylation, which is undesirable because it could affect its biological activity by causing structural changes to the protein. The hydroxylated TiO2 surface shows a greater affinity for HMGB1 than the non-hydroxylated surface. The water layer on the non-hydroxylated TiO2 surface prevents ions and the protein from directly contacting the surface. However, it was observed that if the ionic strength increases, the total number of ions adsorbed on the two surfaces increases, and the protein’s direct adsorption ability decreases. These findings will help to understand the HMGB1-TiO2 interactions upon implantation, as well as the development of different surface strategies by introducing ions or ionic materials to the titanium implant surface to modulate its interactions with HMGB1 to preserve biological function.</div

Dicationic Imidazolium-Based Ionic Liquid Coatings on Zirconia Surfaces: Physico-Chemical and Biological Characterization

In the present work, dicationic imidazolium-based ionic liquids (ILs) were investigated as multi-functional coatings on a zirconia (ZrO2) surface to prevent biofilm formation and enhance the wear performance of zirconia while maintaining the material’s compatibility with host cells. ILs containing phenylalanine and methionine were synthesized and deposited on zirconia. Intermolecular interactions driving IL deposition on zirconia were studied using X-ray photoelectron spectroscopy (XPS). Anti-biofilm activity and cell compatibility were evaluated in vitro after one and seven days, and wear performance was tested using a pin-on-disk apparatus. ILs were observed to form strong hydrogen bonds with zirconia. IL containing phenylalanine formed a stable film on the surface after one and seven days in phosphate-buffered saline (PBS) and artificial saliva and showed excellent anti-biofilm properties against Streptococcus salivarius and Streptococcus sanguinis. Compatibility with gingival fibroblasts and pre-osteoblasts was maintained, and conditions for growth and differentiation were preserved. A significantly lower coefficient of friction and wear volume loss were observed for IL-coated surfaces as compared to non-coated substrates. Overall, zirconia is an emerging alternative to titanium in dental implants systems, and this study provides additional evidence of the materials’ behavior and IL coatings as a potential surface treatment technology for improvement of its properties