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  • 1. Hjalmarsson, Lars
    et al.
    Smedberg, Jan-Ivan
    Pettersson, Mattias
    Specialist Prosthetic Clinic, Public Dental Health Service, St. Erik Hospital, Stockholm, Sweden.
    Jemt, Torsten
    Implant-Level Prostheses in the Edentulous Maxilla: A Comparison with Conventional Abutment-Level Prostheses After 5 Years of Use2011Ingår i: International Journal of Prosthodontics, ISSN 0893-2174, E-ISSN 1139-9791, Vol. 24, nr 2, s. 158-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Long-term comparisons of frameworks at the implant or abutment level are not available, and knowledge of the clinical function of cobalt-chromium (Co-Cr) alloy frameworks is limited. Primarily, the aim of this study was to compare the 5-year clinical performance of frameworks with or without abutment connections to implants. Secondly, the outcomes of prostheses made from Co-Cr alloy with porcelain veneers to those made of commercially pure titanium (CP Ti) with acrylic veneers were compared.

    Materials and Methods: The test groups comprised patients treated with screw-retained fixed prostheses made at the implant level according to the Cresco method in either dental porcelain–veneered Co-Cr alloy (n = 15) or acrylic-veneered CP Ti (n = 25). A control group of 40 randomly selected patients were provided with prostheses made at the standard abutment level in CP Ti with acrylic veneers. For all patients, clinical and radiologic 5-year data were retrospectively collected and evaluated.

    Results: Five-year implant cumulative survival rates (CSRs) were 98.6% and 97.6% for test and control groups, respectively (P > .05). No major differences in bone level were demonstrated between the groups after 5 years (P > .05). Significantly more complications occurred in the test groups compared to the control group (P < .01), with the most common complications being mucositis and fracture of veneers.

    Conclusions: After 5 years, the clinical outcomes of implant-level prostheses made of porcelain-veneered Co-Cr or acrylic-veneered CP Ti seem comparable to acrylic-veneered titanium prostheses made at the standard abutment level regarding implant CSR and bone levels. However, more complications were registered in implant-level prostheses compared to the standard abutment-level prostheses.

  • 2.
    Pettersson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    On titanium release from dental implants and the inflammatory response2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In dentistry, dental implants have become a standard treatment for single tooth loss and partial and total edentulism since their introduction by P-I Brånemark in the 1960s. Long-term follow-up studies have shown that dental implantation is a predictable treatment, with an overall implant survival over ninety-five percent. Mucositis and peri-implantitis are types of inflammation in the peri-implant soft tissue, and the latter occurs with the simultaneous loss of supporting bone. The pathogenesis of mucositis and peri-implantitis is considered a microbial infection in the peri-implant tissue that causes bone loss induced by inflammation. Immune and resident cells are activated by bacterial products and toxins, which induce the release of a cascade of proinflammatory cytokines and chemokines that can activate osteoclasts and cause further bone resorption. Noninfection-induced inflammatory reactions caused by wear particles from an orthopedic implant leading to loss of the prosthesis is a well-known condition in orthopedics. This immune response induced by metal particles has been shown to act by the assembly of a protein complex, i.e., an inflammasome, in macrophages, leading to the release of proinflammatory cytokines, e.g., interleukin 1 beta (IL-1β). Whether metal particles from a dental implant are associated in the pathogenesis of peri-implantitis has not yet been investigated thoroughly. Although titanium dioxide (TiO2) nanoparticles are known to induce a proinflammatory response, the relation between titanium (Ti) and peri-implantitis is not known.

    The overall aim of this thesis was to gain knowledge of the proinflammatory capacity of Ti and its potential association with the pathogenesis of peri-implantitis. The null hypothesis in this thesis is that Ti has no proinflammatory effect.

    To investigate the proinflammatory capacity of Ti, we exposed macrophages derived from a human cell line and monocytes isolated from human blood to Ti. We identified the activation and release of the proinflammatory cytokine IL-1β after the exposure of human macrophages to Ti ions, indicating activation of the inflammasome complex. A five-fold increase in the release of IL-β was found when cells were primed with bacterial products, e.g., Escherichia coli lipopolysaccharide (E. coli LPS) prior to exposure to Ti in culture medium. The proinflammatory effect of Ti was shown to be mediated by metal-protein aggregates formed in the medium and phagocytosed by macrophages. 

    The exposure of macrophages to E. coli LPS mediates the production of intracellular pro-IL-1β, and a second stimulus is needed to cleave the proform of the cytokine, resulting in active IL-1β. Caspase-1, an intracellular protein, is activated through the assembly of the inflammasome complex and is needed for the activation of pro-IL-1β into its active form. Our findings indicate that the Ti-induced activation and release of IL-1β is mediated through the inflammasome complex, as the effect was reduced in the presence of a caspase-1 inhibitor. Peri-implantitis and periodontitis soft tissue samples were investigated chemically and microscopically, and a high content of Ti could be identified in the peri-implantitis tissue samples. The Ti particles identified in the peri-implantitis soft tissue might aggravate the inflammatory response and jeopardize the peri-implant treatment outcome. Transmission electron microscopy (TEM) was used to visualize the formed Ti-protein aggregates, and we discovered that the morphology of the aggregates differed in the presence of cobalt (Co). By microscopy, we could show the uptake of Ti-protein aggregates into macrophage phagolysosomes and that the location of these aggregates differed when Co was present. The origin of the Ti particles found in peri-implantitis soft tissue is unknown, but we could show that Ti is abraded from the implant during insertion into the bone. This abrasion of Ti from the implant surface into the bone is more prominent from an implant with a rough surface than with a smooth surface. 

    We can conclude that Ti can act as a secondary stimulus to macrophages and activate the release of active IL-1β via inflammasome complex assembly. Additionally, Ti forms metal-protein aggregates with a proinflammatory effect that can be inhibited by the presence of Co. Peri-implantitis soft tissue samples contained high concentrations of Ti and metal fragments. Lastly, Ti particles are abraded from the implant during insertion into the bone in amounts that could be proinflammatory. The proinflammatory effect induced by Ti can act in synergy with infection-induced inflammation and cause an imbalance in the host response, leading to the progression of peri-implantitis. The null hypothesis could be rejected.

  • 3.
    Pettersson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Belibasakis, G. N.
    University of Zurich.
    Bylund, D.
    Mittuniversitetet Sundsvall.
    Molin Thorén, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Titanium ions form particles that activate and execute interleukin-1β release from lipopolysaccharide-primed macrophages2017Ingår i: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 52, nr 1, s. 21-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Peri-implantitis is a destructive inflammatory process characterized by destruction of the implant-supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri-implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples.

    MATERIAL AND METHODS: Human macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell-culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin-1β (IL-1β) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively.

    RESULTS: Ti ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL-1β release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 μm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 μm) to stimulate secretion of IL-1β from human macrophages in vitro.

    CONCLUSION: Ti ions form particles that act as secondary stimuli for a proinflammatory reaction.

  • 4.
    Pettersson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Pettersson, Jean
    Department of Chemistry - BMC, Analytical Chemistry, Uppsala, University.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Molin Thorén, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Titanium release in peri-implantitis2019Ingår i: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842, Vol. 46, nr 2, s. 179-188Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or periodontitis and to examine whether Ti particles can be identified in samples from peri-implantitis lesions.

    Background: Long-term follow-up studies show that implant usage to replace missing or lost teeth is a safe and predictable treatment. However, inflammation and loss of supporting bone around an implant (peri-implantitis) lead to patient suffering and costs. Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis tissue is unknown.

    Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analyzed with inductively coupled plasma mass spectrometry (ICP-MS) for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analyzed microscopically with light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) with element analysis to investigate the presence of particulate Ti.

    Results: All patients lost one or more implants despite undergoing peri-implant or periodontal treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than periodontitis tissue with a mean ± SDof 98.7 ± 85.6 μg/g and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and periodontitis biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue. The mean size ± SDof the visible particles with LM was 10.9 ± 35.7 μm2 (mean of three repeated measurements) (95% CI, 6.5-15.3).

    Conclusion: We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions.

  • 5.
    Pettersson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Pettersson, Jean
    Department of Chemistry - BMC, Analytical Chemistry, Uppsala, University.
    Molin Thorén, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Effect of cobalt ions on the interaction between macrophages and titanium2018Ingår i: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, nr 9, s. 2518-2530Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inflammation and bone reduction around dental implants are described as periimplantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL-1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro-inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP-1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL-1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy (ICP-AES) and electron microscopy. Co at a concentration of 100 μM neutralized the IL-1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti-induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti-induced activation and release of active IL-1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal-protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localization after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri-implant tissue.

  • 6.
    Pettersson, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Pettersson, Jean
    Analytic Chemistry, BMC, Department of Chemistry, Uppsala University, Sweden.
    Molin Thorén, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Release of titanium after insertion of dental implants with different surface characteristics: an ex vivo animal study2017Ingår i: Acta Biomaterialia Odontologica Scandinavica, ISSN 0001-5369, E-ISSN 2333-7931, Vol. 3, nr 1, s. 63-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the present study, amount of titanium (Ti) released into the surrounding bone during placement of implants with different surface structure was investigated. Quantification of Ti released during insertion from three different implants was performed in this ex vivo study. Jaw bone from pigs was used as model for installation of the implants and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) was used for analysis of the released Ti. Implant surface were examined with scanning electron microscopy (SEM), before and after the placement into the bone. Ti was abraded to the surrounding bone upon insertion of a dental implant and the surface roughness of the implant increased the amount of Ti found. Diameter and total area of the implant were of less importance for the Ti released to the bone. No visible damages to the implant surfaces could be identified in SEM after placement.

  • 7. Ågren, Martin
    et al.
    Sahin, Christofer
    Pettersson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    The effect of botulinum toxin injections on bruxism: A systematic review2019Ingår i: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Botulinum neurotoxins are produced by the gram-positive anaerobic bacteria Clostridium botulinum, of which several different serotypes have been identified 1,2 . Botulinum neurotoxin type A (BTA) is clinically used the most due to the longer duration of its effect 3,4 and is the focus of this article. One of the first to investigate BTA was Brooks, as he in 1953, showed that when injecting BTA in muscle tissue it inhibited the release of Acetylcholine (ACh) at the neuromuscular junction and rendered motor nerve filaments unexcitable 3 . It has since been shown that BTA inhibits synaptosomal nerve-associated protein 25 (SNAP-25), a protein involved in the release of ACh filled vesicles into the synaptic cleft through the assembly of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNARE) complex, which is necessary for docking and fusing neurotransmitter vesicles with neuronal membranes.

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