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| 2. |
- Hulsart-Billstrom, Gry, 1982-, et al.
(author)
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Guiding bone formation using semi‐onlay calcium phosphate implants in an ovine calvarial model
- 2022
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In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 16:5, s. 435-447
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Journal article (peer-reviewed)abstract
- The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ-CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone-implant contact was found for the CaP (78%, range 14%–94%) versus the Titanium (29%, range 0%–75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material-filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.
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| 3. |
- Engstrand, Johanna, et al.
(author)
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Influence of water content on hardening and handling of a premixed calcium phosphate cement
- 2013
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 33:1, s. 527-531
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Journal article (peer-reviewed)abstract
- Handling of calcium phosphate cements is difficult, where problems often arise during mixing, transferring tosyringes, and subsequent injection. Via the use of premixed cements the risk of handling complications is reduced. However, for premixed cements to work in a clinical situation the setting time needs to be improved. The objective of this study is to investigate the influence of the addition of water on the properties of premixed cement. Monetite-forming premixed cements with small amounts of added water (less than 6.8 wt.%) were prepared and the influence on injectability, working time, setting time and mechanical strength was evaluated. The results showed that the addition of small amounts of water had significant influence on the properties of the premixed cement. With the addition of just 1.7 wt.% water, the force needed to extrude the cement from a syringe was reduced from 107 (±15)N to 39 (±9)N, the compression strength was almost doubled, and the setting time decreased from 29 (±4)min to 19 (±2)min, while the working time remained 5 to 6 h. This study demonstrates the importance of controlling the water content in premixed cement pastes and how water can be used to improve the properties of premixed cements.
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| 4. |
- Gallinetti, Sara, 1985-, et al.
(author)
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Titanium reinforced calcium phosphate improves bone formation and osteointegration in ovine calvaria defects : a comparative 52 weeks study
- 2021
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In: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3
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Journal article (peer-reviewed)abstract
- In a 52 week ovine calvaria implantation model, the restoration of cranial defects with a bare titanium mesh (Ti-mesh) and a titanium mesh embedded in a calcium phosphate (CaP-Ti) were evaluated in seven animals. During the study, no major clinical abnormalities were observed, and all sheep presented a normal neurologic assessment. Blood and cerebrospinal fluid analysis, made at termination, did not show any abnormalities. No indentation of the soft tissue was observed for either test article; however, the Ti-mesh burr-hole covers were associated with filling of the calvarial defect by fibrous tissue mainly. Some bone formation was observed at the bottom of the created defect, but no significant bone was formed in the proximity of the implant. The defect sites implanted with CaP-Ti were characterized by a moderate degradation of the calcium phosphate (CaP) that was replaced by mature bone tissue. Calcium-phosphate-filled macrophages were observed in all animals, indicating that they might play a vital role in osteogenesis. The newly formed bone was present, especially at the bony edges of the defect and on the dura side. Integration of the Ti-mesh in a CaP improved bone formation and osteointegration in comparison to a bare Ti-mesh.
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| 6. |
- Guillet, Claire, et al.
(author)
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Bone formation beyond the skeletal envelope using calcium phosphate granules packed into a collagen pouch-a pilot study
- 2023
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In: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 18:3
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Journal article (peer-reviewed)abstract
- In this proof-of-concept, bone neoformation beyond the skeletal envelope is explored by using a collagen pouch (n = 6) packed with calcium phosphate (CaP) granules placed over the frontal bone in sheep (n = 3). At 13 weeks, macroscopic examination showed specimens covered by an adherent fibrinous envelope with slight vascularization. Histology revealed colonization of the implant by newly formed woven bone and fibrous connective tissue. Surface osteoblasts as well as material-filled macrophages, lymphocytes, polymorphonuclear cells and giant cells were also found in large quantities surrounding the newly formed bone tissue inside the collagen pouch. On the side facing the recipient bone, the collagen membrane had to a large extent been resorbed and bridging bone formation was clearly visible between the test article and recipient bone. On the other side facing soft tissue, the collagen pouch remained intact with a visible fibrous capsule. This study demonstrated that the use of a collagen sleeve as a container for CaP granules allows for good neoformation beyond the skeletal envelope with bridging bone formation clearly visible between the test article and recipient bone. Additionally, in this model, macrophages rather than osteoclasts appear to modulate CaP granule resorption and remodeling into new bone. This construct opens new perspectives for treatment methods that could be used for bone augmentation and restoration of cranio-maxillofacial defects and malformations.
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| 7. |
- Lewin, Susanne, et al.
(author)
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Additively manufactured mesh-type titanium structures for cranial implants : E-PBF vs. L-PBF
- 2021
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In: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 197
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Journal article (peer-reviewed)abstract
- A patient-specific titanium-reinforced calcium phosphate (CaP–Ti) cranial implant has recently shown promising clinical results. Currently, its mesh-type titanium structure is additively manufactured using laser beam powder bed fusion (L-PBF). Nevertheless, an electron-beam (E-PBF) process could potentially be more time efficient. This study aimed to compare the geometrical accuracy and mechanical response of thin titanium structures manufactured by L-PBF (HIPed) and E-PBF (as-printed). Tensile test (ø = 1.2 mm) and implant specimens were manufactured. Measurements by μCT revealed a deviation in cross-sectional area as compared to the designed geometry: 13–35% for E-PBF and below 2% for L-PBF. A superior mechanical strength was obtained for the L-PBF specimens, both in the tensile test and the implant compression tests. The global peak load in the implant test was 457 ± 9 N and 846 ± 40 N for E-PBF and L-PBF, respectively. Numerical simulations demonstrated that geometrical deviation was the main factor in implant performance and enabled quantification of this effect: 34–39% reduction in initial peak force based on geometry, and only 11–16% reduction based on the material input. In summary, the study reveals an uncertainty in accuracy when structures of sizes relevant to mesh-type cranial implants are printed by the E-PBF method.
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| 8. |
- Lewin, Susanne, et al.
(author)
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Mechanical behaviour of composite calcium phosphate-titanium cranial implants : Effects of loading rate and design
- 2020
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In: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 104
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Journal article (peer-reviewed)abstract
- Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate-titanium (CaP-Ti) implant at quasi-static and impact loading rates. Two different designs were tested, referred to as Design 1 (D1) and Design 2 (D2). The titanium structures in the implant specimens were additively manufactured by a powder-bed fusion process and subsequently embedded in a self-setting CaP material. D1 was conceptually representative of the clinically used implants. In D2, the titanium structure was simplified in terms of geometry in order to facilitate the manufacturing. The mechanical response of the implants was evaluated in quasi-static compression, and in impact using a drop-tower. Similar peak loads were obtained for the two designs, at the two loading rates: 808 ± 29 N and 852 ± 34 for D1, and 840 ± 40 N and 814 ± 13 for D2. A strain rate dependency was demonstrated for both designs, with a higher stiffness in the impact test. Furthermore, the titanium in the implant fractured in the quasi-static test (to failure) but not in the impact test (to 5.75 J) for D1. For D2, the displacement at peak load was significantly lower in the impact test than in the quasi-static test. The main difference between the designs was seen in the quasi-static test results where the deformation zones, i.e. notches in the titanium structure between the CaP tiles, in D1 likely resulted in a localization of the deformation, compared to in D2 (which did not have deformation zones). In the impact test, the only significant difference between the designs was a higher maximum displacement of D2 than of D1. In comparison with other reported mechanical tests on osteoconductive ceramic-based cranial implants, the CaP-Ti implant demonstrates the highest reported strength in quasi-static compression. In conclusion, the titanium structure seems to make the CaP-Ti implant capable of cerebral protection in impact situations like the one tested in this study.
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| 9. |
- Lewin, Susanne, et al.
(author)
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Monetite-based composite cranial implants demonstrate long-term clinical volumetric balance by concomitant bone formation and degradation
- 2021
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In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 128, s. 502-513
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Journal article (peer-reviewed)abstract
- The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation. In this study, the volumetric change at the implant site was quantified longitudinally by clinical computed tomography (CT). The retrospective CT datasets had been acquired postoperatively ( n = 10), in 1-year ( n = 9) and 3-year ( n = 5) follow-ups. In the 1-year follow-up, the total volumetric change at the implant site was-8 +/- 8%. A volumetric increase (bone formation) was found in the implant-bone interface, and a volumetric decrease was observed in the central region (CaP degradation). In the subjects with 2-or 3-year follow-ups, the rate of volumetric decrease slowed down or plateaued. The reported degradation rate is lower than previous clinical studies on monetite, likely due to the presence of pyrophosphate in the monetite-based CaP-formulation. A 31-months retrieval specimen analysis demonstrated that parts of the CaP had been remodeled into bone. The CaP phase composition remained stable, with 6% transformation into hydroxyapatite. In conclusion, this study demonstrates successful bone-bonding between the CaP-material and the recipient bone, as well as a long-term volumetric balance in cranial defects repaired with the monetitebased composite implant, which motivates further clinical use. The developed methods could be used in future studies for correlating spatiotemporal information regarding bone regeneration and CaP degradation to e.g. patient demographics. Statement of significance In bone defect reconstructions, the use of calcium phosphate (CaP) bioceramics ideally results in a volumetric balance between bone formation and CaP degradation. Clinical data on the volumetric balance is nevertheless lacking, especially for monetite-based CaPs. Here, this concept is investigated for a composite cranial implant. The implant volumes were quantified from clinical CT-data: postoperatively, one year and three years postoperatively. In total,-8 +/- 8% ( n = 9) volumetric change was observed after one year. But the change plateaued, with only 2% additional decrease at the 3-year follow-up ( n = 5), indicating a lower CaP degradation rate. Osseointegration was seen at the bone-implant interface, with a 9 +/- 7% volumetric change after one year. This study presented the first quantitative spatiotemporal CT analysis of monetite-based CaPs.
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| 10. |
- Lundberg, Christina, et al.
(author)
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Age and sex differences in cause-specific excess mortality and years of life lost associated with COVID-19 infection in the Swedish population
- 2023
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In: European Journal of Public Health. - : OXFORD UNIV PRESS. - 1101-1262 .- 1464-360X. ; 33:5, s. 916-22
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Journal article (peer-reviewed)abstract
- Background Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic. Methods In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017-19 in the whole Swedish population. Results COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65-110 years and women aged 75-110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020. Conclusions Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19.
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