| 1. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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Molecular Response to Nanopatterned Implants in the Human Jaw Bone
- 2021
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Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:12, s. 5878-5889
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Tidskriftsartikel (refereegranskat)abstract
- Implant surface modification by nanopatterning is an interesting route for enhancing osseointegration in humans. Herein, the molecular response to an intentional, controlled nanotopography pattern superimposed on screw-shaped titanium implants is investigated in human bone. When clinical implants are installed, additional two mini-implants, one with a machined surface (M) and one with a machined surface superimposed with a hemispherical nanopattern (MN), are installed in the posterior maxilla. In the second-stage surgery, after 6-8 weeks, the mini-implants are retrieved by unscrewing, and the implant-adherent cells are subjected to gene expression analysis using quantitative polymerase chain reaction (qPCR). Compared to those adherent to the machined (M) implants, the cells adherent to the nanopatterned (MN) implants demonstrate significant upregulation (1.8- to 2-fold) of bone-related genes (RUNX2, ALP, and OC). No significant differences are observed in the expression of the analyzed inflammatory and remodeling genes. Correlation analysis reveals that older patient age is associated with increased expression of proinflammatory cytokines (TNF-alpha and MCP-1) on the machined implants and decreased expression of proosteogenic factor (BMP-2) on the nanopatterned implants. Controlled nanotopography, in the form of hemispherical 60 nm protrusions, promotes gene expressions related to early osteogenic differentiation and osteoblastic activity in implant-adherent cells in the human jaw bone.
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| 2. |
- Karazisis, Dimitrios, 1977
(författare)
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On osseointegration in response to controlled surface nanotopography
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge about the biological responses provoked by the surface modification of titanium implants on the nanoscale is still in its infancy. Although in vitro studies claim superior effects considering higher adhesion and proliferation of osteoblasts in the short term and even differentiation towards the osteogenic cell lineage in the long term, these responses do not necessarily reflect the actual outcome in the complex in vivo environment. Therefore, the main aim of this thesis was to evaluate the biological responses at the bone interface to titanium implants with controlled surface nanotopography. Both very early and late healing events were considered, and the phases of acute inflammation, bone regeneration and bone remodeling were evaluated, first in the rat tibia and thereafter in human maxillary bone. This was performed by screening and quantification of genes of interest, representing the different healing phases, by quantitative polymerase chain reaction (qPCR), and correlating these molecular events to morphological (histology and histomorphometry) and biomechanical (removal torque) outcomes of osseointegration. The first study used a specially designed implant with nanopatterns only at the cylindrical part facing the bone marrow and not the threads that were engaging the cortical bone. Analyses showed that the gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and osteoclast marker cathepsin K (CatK) was downregulated at the nanopatterned implants at 3 and 6 days, respectively. This finding was consistent with fewer CD163-positive macrophages in the peri-implant tissue. Due to improved methodology, the nanopatterns could be applied to complex screw-shaped implants resembling clinical dental implants and used in the second, third and fourth studies. In the second study, evaluating the very early tissue-implant interactions, nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1) at 12 hours and triggered the expression of osteocalcin (OC) at 3 days. This was in parallel with a relatively lower number of CD68-positive monocytes and a higher proportion of early-formed bone. In the third study, it was demonstrated that the nanotopography could downregulate the expression of the proinflammatory cytokine TNF-α even after 21 days. Osteoclastogenesis molecular activity was down-regulated at implants with combined nano- and microtopography at 6 days. A synergistic effect was disclosed, with the combination of micro- and nanotopography further attenuating the inflammatory response via TNF-α downregulation and resulting in an increased biomechanical stability, as judged by higher removal torque values. A human study showed that implants with nanotopography significantly increased the expression of all the targeted osteoblastic markers, namely, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) and OC, suggesting the promotion of bone formation. In conclusion, nanotopography per se, attenuates the initial inflammatory response and increases bone formation while down-regulating osteoclastogenesis and bone resorption molecular activities. Furthermore, the combined effect of micro- and nanotopography can further attenuate the inflammatory response and enhance the mechanical stability of the implants.
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| 3. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
-
The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 136, s. 279-290
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Tidskriftsartikel (refereegranskat)abstract
- The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.
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