| 1. |
- Palmquist, Anders, 1977, et al.
(författare)
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Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants
- 2023
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
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Forskningsöversikt (refereegranskat)abstract
- The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
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| 2. |
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| 3. |
- Micheletti, Chiara, et al.
(författare)
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Ultrastructure and Nanoporosity of Human Bone Shown with Correlative On-Axis Electron and Spectroscopic Tomographies
- 2023
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Ingår i: ACS Nano. - 1936-0851 .- 1936-086X. ; 17:24
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Tidskriftsartikel (refereegranskat)abstract
- Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with diameters up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: (i) low-contrast nanosized circular spaces (“holes”) observed in sections of bone oriented perpendicular to the long axis of a long bone, and (ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most “holes” are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears to be composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signatures (Ca and P) within the gap zones, but the signal appears weaker than that associated with the extra-fibrillar mineral, pointing toward the existence of dissimilarities between the two types of mineralization.
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| 4. |
- Karlsson, Johan, 1984, et al.
(författare)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Tidskriftsartikel (refereegranskat)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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| 5. |
- Thorfve, Anna, 1982, et al.
(författare)
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Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo
- 2014
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li+). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction. HA-coated implants showed, irrespective of Li+ content, bone-implant contact (BIC) and removal torque significantly higher than those of reference Ti. Further, the expressions of OCN, CTSK, COL1A1, LRP5/6 and WISP1 were significantly higher in implant-adherent cells of HA-coated implants, with or without Li+. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14ngcm-2 released Li+. Interestingly, Ti implants showed a significantly larger bone area in the threads than HA with 39ngcm-2 released Li+, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li+ is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.
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| 6. |
- Öhrnell Malekzadeh, Behnosh, et al.
(författare)
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Effects of implant-delivered insulin on bone formation in osteoporotic rats
- 2018
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 106:9, s. 2472-80
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Wiley Periodicals, Inc. Osteoporosis is a major cause of age-related fractures. Healing complications in osteoporotic patients are often associated with increased mortality and morbidity. Stimulation of the implant-adjacent bone could be beneficial in terms of the surgical outcome. Over the past decade, numerous investigations have implicated insulin in normal bone growth, and recent studies have described the advantages of administering insulin locally to increase bone formation. Therefore, we hypothesized that insulin-coated titanium implants would increase bone formation in osteoporotic animals. The aim of this study was to evaluate the effects of insulin delivered from an implant surface on bone-related gene expression and bone formation in osteoporotic rats. Characterizations of the surfaces of insulin-coated and control implants were performed using ellipsometry and interferometry. Forty ovariectomized and four healthy Sprague Dawley rats were used and implants were inserted in the tibias. The systemic effect of insulin was assessed by measuring the blood glucose levels and total body weight. The animals were sacrificed either 1 day or 3 weeks postimplantation. Implant-adherent cells were analyzed by quantitative real-time PCR, and the bone adjacent to the implants was examined by microcomputed tomography and histomorphometry. The insulin-coated implants had no systemic effects. The insulin-coated samples demonstrated significantly lower expression of the gene for interleukin 1β (p=0.019) at 1 day, and significantly exhibited more periosteal callus (p=0.029) at 3 weeks. Locally delivered insulin has potential for promoting bone formation and it exerts potentially anti-inflammatory effects in osteoporotic rats.
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| 7. |
- Akman, Adnan, et al.
(författare)
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Effect of minor gallium addition on corrosion, passivity, and antibacterial behaviour of novel β-type Ti–Nb alloys
- 2023
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Ingår i: Journal of Materials Research and Technology. - 2238-7854. ; 25, s. 4110-4124
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Tidskriftsartikel (refereegranskat)abstract
- Metastable Ti–Nb alloys are promising bone-implant materials due to improved mechanical biofunctionality and biocompatibility. To overcome increasing bacterial infection risk, alloying with antibacterial elements is a promising strategy. This study investigates the effect of minor gallium (Ga) additions (4, 8 wt% Ga) to as-cast and solution-treated β-type Ti–45Nb-based alloy (96(Ti–45Nb)-4Ga, 92(Ti–45Nb)-8Ga (wt.%)) on corrosion and passive film properties, as well as cytocompatibility and antibacterial activity. The electrochemical properties were evaluated by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott-Schottky analyses in phosphate-buffered saline (PBS). X-ray photoelectron spectroscopy (XPS) was performed to analyze the chemical composition of passive films. Early adhesion and viability of macrophages and Staphylococcus aureus were assessed by nucleocounting and colony-forming unit counting, respectively. The results showed that high corrosion resistance and passive film properties of Ti–45Nb are retained and even slightly improved with Ga. EIS results revealed that Ga addition improves the passive film resistance. XPS measurements of 92(Ti–45Nb)-8Ga show that the passive film contains Ti-, Nb- and Ga-based oxides, implying the formation of mixed (Ti–Nb-Ga) oxides. In addition, marginal Ga ion release rate was detected under free corrosion conditions. Therefore, it can be assumed that Ga species may contribute to passive film formation on Ga-containing alloys. The 92(Ti–45Nb)-8Ga elicited an antibacterial effect against S. aureus compared to cp-Ti at 4 h. Moreover, Ga-containing alloys showed good cytocompatibility with THP-1 macrophages at 24 h. In conclusion, it was demonstrated that Ga additions to Ti–45Nb are beneficial to corrosion resistance and showed promising initial host and bacterial interactions.
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| 8. |
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| 9. |
- Ballo, Ahmed, 1978, et al.
(författare)
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Bone response to physical-vapour-deposited titanium dioxide coatings on titanium implants
- 2013
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 24:9, s. 1009-1017
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate the correlation between coating thickness and the crystal structure of physical-vapour-deposited (PVD) titanium dioxide coatings, and to evaluate their in vivo biocompatibility. Materials and methods: The PVD TiO 2 coatings of different thickness were deposited on machined titanium grade 2 screw-shaped implants. Non-coated titanium implants were used as controls. Coating properties such as thickness, crystal structure, coating morphology and roughness were characterized. Forty-eight implants were placed randomly into both tibias of 16 rats. The animals were euthanized 7 and 28 days postsurgery and block biopsies were prepared for histology, histomorphometry and SEM analysis. Results: The thicknesses of the PVDTiO 2 coatings were 120 and 1430 nm respectively. Histologically, new bone formed on all implant surfaces. The mean percentage of newly formed bone in contact with the implant (BIC) was significantly higher at early healing time (7 days) for the 120 nm thick PVD coating (39 ± 14%) than for both the 1430 nm thick PVD coating (22 ± 10%) (P = 0.043) and the machined surface (22 ± 9%) (P = 0.028). This difference was no longer evident after 28 days (P = 0.867). Conclusion: Bone formation and bone-to-implant contact are achieved to the same degree for TiO 2 surface modifications prepared by a PVD process as clinically used, machined titanium. Furthermore, a relatively thinner PVD coating promotes a higher degree of bone apposition shortly after implantation, thereby providing rationales for exploring the potential clinical use of these modifications.
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| 10. |
- Ballo, Ahmed, 1978, et al.
(författare)
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Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:72, s. 1615-1624
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the bone tissue response to strontium-and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone-implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.
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