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- Karazisis, Dimitrios, 1977, et al.
(författare)
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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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| 2. |
- Andersson, Marcus, 1975, et al.
(författare)
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Effect of molecular mobility of polymeric implants on soft tissue reactions: An in vivo study in rats
- 2008
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Ingår i: Journal of Biomedical Materials Research Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 84A:3, s. 652-660
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Tidskriftsartikel (refereegranskat)abstract
- Although numerous different polymers are used as implants or otherwise studied for many other biotechnical applications, there is a lack of basic models that correlate polymer characteristics with foreign body reactions. This study aims at developing one such model by systematically studying surface molecular mobility of polymeric implants in soft tissues in vivo. Changing the length of the alkyl side chain of poly(alkyl methacrylates) (PAMAs), provides an interesting opportunity to study the surface molecular mobility with minimal changes of the hydrophobicity of the surface. Thus, in this study three different PAMAs, with increasingly surface mobility; poly (isobutyl methacrylate) (PIBMA), poly(butyl methacrylate) (PBMA), and poly(lauryl methacralate) (PLMA) along with pure titanium (Ti) substrates were implanted in the dorsum of Sprague-Dawley rats. Inflammatory cell recruitment, cell adhesion, and cytokine release were studied after 1, 3, and 28 days of implantation. Total number of inflammatory cells in the exudate was measured but no correlation between surface mobility and cell recruitment where found. However, the number of surface associated cells where significantly lower on the surfaces with high molecular mobility (PLMA and PBMA). The histological evaluation performed after 28 days revealed thicker fibrous capsule and a higher number of blood vessels on the low molecular mobility surface (PIBMA). After 28 days the cell activity was higher on the high molecular mobility surfaces (PLMA and PBMA) compared with PIBMA, based on the cytokine release. None of the surfaces induced any significant cell-death. On the basis of the results of this study we conclude that there is a significant difference in biological response to surfaces with different in molecular mobility. This might affect the wound healing process and the biocompatibility of biomaterials. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007 -------------------------------------------------------------------------------- Received: 13 March 2006; Revised: 15 December 2006; Accepted: 29 January 2007 Digital Object Identifier (DOI) 10.1002/jbm.a.31389 About DOI
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| 3. |
- Suska, Felicia, 1974, et al.
(författare)
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Fibrous capsule formation around titanium and copper.
- 2008
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Ingår i: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296 .- 1552-4965 .- 0021-9304 .- 1097-4636. ; 85:4, s. 888-96
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest that implant material properties influence the quality and quantity of fibrous capsule around the implant. However, the precise relation between material surface chemistry, early inflammatory response, and fibrous subsequent repair outcome is still unknown. Titanium (Ti) and copper (Cu), surfaces with different inflammatory potential, were implanted subcutaneously in rats and retrieved fibrous capsules were analyzed after 28 and 56 days. Histological examinations show pronounced differences in capsule morphology. The fibrous capsule around Ti was thinner than that around Cu, with less number of the inflammatory cells in the layer close to the implant surface, and less and smaller blood vessels. The capsule around Cu was thick, with a large number of the inflammatory cells, particularly macrophages and giant cells, and increased number of blood vessels. Our study suggests that material surface properties, which initiate early, multiple cellular inflammatory events, are also associated with increased fibrosis and angiogenesis during repair phase. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.
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| 5. |
- Svensson, Sara, 1981, et al.
(författare)
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Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation
- 2022
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Ingår i: Journal of Materials Science-Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-gamma) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 mu M) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression.
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| 6. |
- Almqvist, Sofia, 1980, et al.
(författare)
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Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured human dermal fibroblasts
- 2010
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Ingår i: Journal of Materials Science. Materials in Medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 μg/ml increased binding of NHDF via several integrins, including αvβ3, αvβ5 and α5β1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix.
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| 9. |
- Almqvist, Sofia, 1980, et al.
(författare)
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In Vitro Effect of Amelogenin on Selected Cell Mediators from Human Monocytes
- 2008
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Ingår i: 8th World Biomaterials Congress, Amsterdam, The Netherlands.
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Konferensbidrag (refereegranskat)abstract
- Introduction: Inflammation is an integral part of the normal wound healing response. Besides clearing the wound of invading microbes and debris, inflammatory cells are believed to be crucial coordinators of the repair process, acting both as phagocytes and as a major source of growth factors and other signals [1]. In non-healing skin ulcers the repair process is stuck in the inflammation phase [2]. Excessive inflammation can reflect an imbalance in the transformation of phenotype between the classically activated, inflammatory macrophage and the alternatively activated macrophage involved in immunosuppression and tissue repair [3]. Amelogenin is a hydrophobic extracellular matrix protein that under physiological conditions will self assemble into nanospheres which in turn may form larger aggregates. Treatment with amelogenin has shown enhanced skin wound healing in an in vivo study in rabbits [4]. In addition, amelogenin has been proposed to have anti-inflammatory properties by attenuation of lipopolysaccharide (LPS)- and peptidoglucan-induced production of selected pro-inflammatory cytokines by human blood cells [5]. The present study was initiated to determine the effects of amelogenin on human monocyte secretion of factors which modulate both inflammation and tissue repair. Materials and Methods: Lyophilized amelogenin from Biora AB (Malmö, Sweden) was dissolved in 17 mM acetic acid. Human monocytes were obtained from six healthy blood donors by isolation using the separation gradient PercollTM in two steps according to Pertoft et al. [6]. The isolated monocytes were cultured for 24 h at 37ºC with 5% CO2 and 95% humidity. Thereafter the supernatants and non-adherent cells were removed. Fresh medium (RPMI, 5% foetal bovine serum, antibiotics) containing amelogenin, 0, 0.01, 0.1 and 1.0 mg/ml, and with or without addition of LPS, was added to the wells in triplicates. The plates were again incubated for 24 h. The supernatants were analyzed with commercial human ELISA assays for tumour necrosis factor- (TNF-), interleukin-10 (IL-10), macrophage inflammatory protein-1 (MIP-1), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and insulin like growth factor-1 (IGF-1). Results: Amelogenin treatment markedly altered the expression of factors by human monocytes. Amelogenin significantly reduced LPS-induced TNF- secretion, whereas the IL-10 expression was increased. Monocyte secretion of the two inflammatory chemokines MIP-1 and MCP-1 (Figure; mean ± SEM, n=6) was also affected by amelogenin treatment. Furthermore, amelogenin significantly increased monocyte secretion of VEGF (Figure; mean ± SEM, n=6) and IGF-1, although to a lesser extent, after 24 h culture. Conclusions: The amelogenin effects correlate to protein concentration, however not in a dose dependent manner, but instead the cell responses may reflect a concentration related difference in self assembly of the amelogenin protein. The observed changes in cytokine and chemokine expression are markedly affected by simultaneous LPS-induced inflammation activation, revealing possible anti-inflammatory properties of the amelogenin protein. In addition, the several-fold increase in VEGF-levels by monocytes provides a possible mechanism for the observed pro-angiogenic effect in vivo [4]. These in vitro results indicate that the extracellular matrix protein amelogenin by virtue of its interaction with human monocytes may modulate inflammation and tissue repair. Acknowledgements: The support from the Swedish Research Council (grant K2006-73X-09495-16-3), Mölnlycke Health Care Group AB and the VINNOVA VinnVäxt Program Biomedical Development in Western Sweden, is gratefully acknowledged. References: 1. Martin, P., et al. Trends Cell Biol., 15, 599, 2005. 2. Ågren, M.S., et al. Acta Derm Venereol Suppl (Stockh). 210, 3, 2000. 3. Duffield, J.S. Clin Sci (Lond), 104, 27, 2003 4. Mirastschijski, U., et al. Wound Repair Regen., 12, 100, 2004. 5. Myhre, A.E., et al. J Periodontal Res., 41, 208, 2006. 6. Pertoft, H., et al. J Immunol Methods., 33, 221, 1980.
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