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      Enhanced VEGF/VEGF-R and RUNX2 Expression in Human Periodontal Ligament Stem Cells Cultured on Sandblasted/Etched Titanium Disk

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          Abstract

          Bone formation, in skeletal development or in osseointegration processes, is the result of interaction between angiogenesis and osteogenesis. To establish osseointegration, cells must attach to the implant in a direct way without any deposition of soft tissue. Structural design and surface topography of dental implants enhance the cell attachment and can affect the biological response. The aim of the study was to evaluate the cytocompatibility, osteogenic and angiogenic markers involved in bone differentiation of human periodontal ligament stem cells (hPDLSCs) on different titanium disks surfaces. The hPDLSCs were cultured on pure titanium surfaces modified with two different procedures, sandblasted (Control—CTRL) and sandblasted/etched (Test—TEST) as experimental titanium surfaces. After 1 and 8 weeks of culture VEGF, VEGF-R, and RUNX2 expression was evaluated under confocal laser scanning microscopy. To confirm the obtained data, RT-PCR and WB analyses were performed in order to evaluate the best implant surface performance. TEST surfaces compared to CTRL titanium surfaces enhanced cell adhesion and increased VEGF and RUNX2 expression. Moreover, titanium TEST surfaces showed a different topographic morphology that promoted cell adhesion, proliferation, and osteogenic/angiogenic commitment. To conclude, TEST surfaces performed more efficiently than CTRL surfaces; furthermore, TEST surface results showed them to be more biocompatible, better tolerated, and appropriate for allowing hPDLSC growth and proliferation. This fact could also lead to more rapid bone–titanium integration.

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          Most cited references 46

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          A review on the wettability of dental implant surfaces II: Biological and clinical aspects.

          Dental and orthopedic implants have been under continuous advancement to improve their interactions with bone and ensure a successful outcome for patients. Surface characteristics such as surface topography and surface chemistry can serve as design tools to enhance the biological response around the implant, with in vitro, in vivo and clinical studies confirming their effects. However, the comprehensive design of implants to promote early and long-term osseointegration requires a better understanding of the role of surface wettability and the mechanisms by which it affects the surrounding biological environment. This review provides a general overview of the available information about the contact angle values of experimental and of marketed implant surfaces, some of the techniques used to modify surface wettability of implants, and results from in vitro and clinical studies. We aim to expand the current understanding on the role of wettability of metallic implants at their interface with blood and the biological milieu, as well as with bacteria, and hard and soft tissues. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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            The roles of vascular endothelial growth factor in bone repair and regeneration.

            Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors.
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              An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration

              Despite considerable recent progress in defining neutrophil functions and behaviors in tissue repair, much remains to be determined with regards to its overall role in the tissue integration of biomaterials. This article provides an overview of the neutrophil’s numerous, important roles in both inflammation and resolution, and subsequently, their role in biomaterial integration. Neutrophils function in three primary capacities: generation of oxidative bursts, release of granules and formation of neutrophil extracellular traps (NETs); these combined functions enable neutrophil involvement in inflammation, macrophage recruitment, M2 macrophage differentiation, resolution of inflammation, angiogenesis, tumor formation and immune system activation. Neutrophils exhibit great flexibility to adjust to the prevalent microenvironmental conditions in the tissue; thus, the biomaterial composition and fabrication will potentially influence neutrophil behavior following confrontation. This review serves to highlight the neutrophil’s plasticity, reiterating that neutrophils are not just simple suicidal killers, but the true maestros of resolution and regeneration.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                14 May 2020
                2020
                : 8
                Affiliations
                1Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara , Chieti, Italy
                2ASL 02 Lanciano-Vasto-Chieti, SS. Annunziata Hospital , Chieti, Italy
                3IRCCS Centro Neurolesi “Bonino-Pulejo ,” Messina, Italy
                Author notes

                Edited by: Giovanna Orsini, Marche Polytechnic University, Italy

                Reviewed by: Barbara Zavan, University of Padua, Italy; Alessandra Pisciotta, University of Modena and Reggio Emilia, Italy

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Stem Cell Research, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00315
                7240029
                Copyright © 2020 Marconi, Diomede, Pizzicannella, Fonticoli, Merciaro, Pierdomenico, Mazzon, Piattelli and Trubiani.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 12, Tables: 0, Equations: 0, References: 58, Pages: 16, Words: 0
                Categories
                Cell and Developmental Biology
                Original Research

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