| 1. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Suska, Felicia, 1974, et al.
(författare)
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In vivo cytokine secretion and NF-kappaB activation around titanium and copper implants.
- 2005
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 26:5, s. 519-27
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Tidskriftsartikel (refereegranskat)abstract
- The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-kappaB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48 h around Cu. A marked decrease of exudate cell viability was found around Cu after 48 h. The total amounts of activated NF-kappaB after 12 h was highest in Ti exudates whereas after 48 h the highest amount of NF-kappaB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-kappaB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo.
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| 5. |
- Shah, Furqan A., et al.
(författare)
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Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting.
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 36:May, s. 296-309
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Tidskriftsartikel (refereegranskat)abstract
- In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39±4%) than CoCr (27±4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications.
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| 6. |
- Palmquist, Anders, 1977, et al.
(författare)
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A technique for evaluating bone ingrowth into 3D printed, porous Ti6Al4V implants accurately using X-ray micro-computed tomography and histomorphometry.
- 2017
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Ingår i: Micron. - : Elsevier BV. - 0968-4328. ; 94, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the application of X-ray micro-computed tomography (micro-CT) to accurately evaluate bone formation within 3D printed, porous Ti6Al4V implants manufactured using Electron Beam Melting (EBM), retrieved after six months of healing in sheep femur and tibia. All samples were scanned twice (i.e., before and after resin embedding), using fast, low-resolution scans (Skyscan 1172; Bruker micro-CT, Kontich, Belgium), and were analysed by 2D and 3D morphometry. The main questions posed were: (i) Can low resolution, fast scans provide morphometric data of bone formed inside (and around) metal implants with a complex, open-pore architecture?, (ii) Can micro-CT be used to accurately quantify both the bone area (BA) and bone-implant contact (BIC)?, (iii) What degree of error is introduced in the quantitative data by varying the threshold values?, and (iv) Does resin embedding influence the accuracy of the analysis? To validate the accuracy of micro-CT measurements, each data set was correlated with a corresponding centrally cut histological section. The results show that quantitative histomorphometry corresponds strongly with 3D measurements made by micro-CT, where a high correlation exists between the two techniques for bone area/volume measurements around and inside the porous network. On the contrary, the direct bone-implant contact is challenging to estimate accurately or reproducibly. Large errors may be introduced in micro-CT measurements when segmentation is performed without calibrating the data set against a corresponding histological section. Generally, the bone area measurement is strongly influenced by the lower threshold limit, while the upper threshold limit has little or no effect. Resin embedding does not compromise the accuracy of micro-CT measurements, although there is a change in the contrast distributions and optimisation of the threshold ranges is required.
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| 7. |
- 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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| 8. |
- Grandfield, Kathryn, et al.
(författare)
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Bone response to free form fabricated hydroxyapatite and zirconia scaffolds : a transmission electron microscopy study in the human maxilla
- 2012
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Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 14:3, s. 461-469
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Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding the interfacial reactions to synthetic bone regenerative scaffolds in vivo is fundamental for improving osseointegration and osteogenesis. Using transmission electron microscopy, it is possible to study the biological response of hydroxyapatite (HA) and zirconia (ZrO2) scaffolds at the nanometer scale.Purpose: In this study, the bone-bonding abilities of HA and ZrO2 scaffolds produced by free-form fabrication were evaluated in the human maxilla at 3 months and 7 months.Materials and Methods: HA and ZrO2 scaffolds (ø: 3 mm) were implanted in the human maxilla, removed with surrounding bone, embedded in resin, and sectioned. A novel focused ion beam (FIB) sample preparation technique enabled the production of thin lamellae for study by scanning transmission electron microscopy.Results: Interface regions were investigated using high-angle annular dark-field imaging and energy-dispersive X-ray spectroscopy analysis. Interfacial apatite layers of 80 nm and 50 nm thickness were noted in the 3- and 7-month HA samples, respectively, and bone growth was discovered in micropores up to 10 µm into the samples.Conclusions: The absence of an interfacial layer in the ZrO2 samples suggest the formation of a direct contact with bone, while HA, which bonds through an apatite layer, shows indications of resorption with increasing implantation time. This study demonstrates the potential of HA and ZrO2 scaffolds for use as bone regenerative materials.
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| 9. |
- Malmström, Johan, 1975, et al.
(författare)
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Bone ingrowth in zirconia and hydroxyapatite scaffolds with identical macroporosity.
- 2008
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 19:9, s. 2983-92
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Tidskriftsartikel (refereegranskat)abstract
- The role of the material composition, porosity and surface topography of scaffolds for promotion of osteogenesis and osseointegration is not fully understood. The aim of the present study was to evaluate the effects of material composition and surface topography on bone ingrowth and bone contact. Designed macroporous ceramic scaffolds of zirconia and hydroxyapatite were used. Using free form fabrication (FFF) techniques an identical macroporosity in both materials was achieved. The scaffolds were implanted in rabbit tibia (cortical bone) and femur (trabecular bone). After 6 weeks of implantation the tissue response was assessed with histology and histomorphometry. The results showed significantly more bone ingrowth and bone contact in the hydroxyapatite scaffolds compared to the zirconia scaffold. Surface topography had no significant effect on bone contact inside the macropores regardless of material. This was observed in both cortical and trabecular bone sites. The study suggests that the difference between hydroxyapatite and zirconia was due to a difference in material chemistry.
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| 10. |
- Omar, Omar, et al.
(författare)
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Integrin and chemokine receptor gene expression in implant-adherent cells during early osseointegration.
- 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, s. 969-80
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of early cellular recruitment and interaction to titanium implants are not well understood. The aim of this study was to investigate the expression of pro-inflammatory cytokines, chemokines and adhesion markers during the first 24 h of implantation. Anodically oxidized and machined titanium implants were inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and analyzed with quantitative polymerase chain reaction. Immunohistochemistry and scanning electron microscopy revealed different cell types, morphology and adhesion at the two implant surfaces. A greater amount of cells, as indicated by higher expression of small subunit ribosomal RNA (18S), was detected on the oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was detected at the oxidized surfaces. Significantly higher tumor necrosis factor-alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for the machined surface. It is concluded that material surface properties rapidly modulate the expression of receptors important for the recruitment and adhesion of cells which are crucial for the inflammatory and regenerative processes at implant surfaces in vivo.
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