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- Ben Amara, Heithem, 1984, et al.
(författare)
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Bone healing around biodegradable Magnesium implants: Differential response between interfacial and near-implant bone in vivo
- 2022
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Ingår i: 14th Symposium on Biodegradable Metals, Alicante, Spain 24-29 August 2022.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: By virtue of their mechanical properties and of their degradation, magnesium (Mg)-based osteosynthesis systems are metallic implants that hold the fractured bones while eliminated in situ, thus offering the promise of reduced complications posed by permanent implants. A growing amount of research validated Mg-based implants for bone fixation by providing robust evidence in support of new bone deposition in contact with the interfacial degradation layer. Whereas Mg-degradation products are known to distribute in the implant environment, less attention has been paid to the bone response at distance from the implant interface. The present study investigated the structural, cellular, and molecular events taking place at the bone-Mg implant interface and at distance from it after in vivo implantation in an experimental rat model. METHODS: Following approval by the Local Ethical Committee at the University of Gothenburg (Dnr: 14790/2019), male Sprague-Dawley rats (n=56) were implanted with miniature screws manufactured from pure magnesium (99.99% - high purity; Mg) or from pure titanium (grade 4; Ti) (herein, serving as a control, enabling osseointegration in this model). In each animal, the metaphysis of the left and right tibiae was drilled prior to the insertion of Ti or Mg screws. After 3 and 28 days, animals were euthanized, and two types of samples were retrieved (Fig. 1): 1-Implants and peri-implant bone for quantitative polymerase chain reaction (qPCR) (n=8/group/time-point): were separately collected and allocated for molecular gene expression of the implant-adherent cells and of the cells in the peri-implant space. 2-Peri-implant bone with implants en bloc for paraffin or plastic embedding (n=6/group/time-point): enabling radiographical analyses using micro-computed tomography (micro-CT) and histomorphometrical measurements of the bone at the implant interface and at distance from it. Statistical comparisons were made between experimental groups at each time point and between time-points for each experimental group. (Kruskal-Wallis, Mann-Whitney and Wilcoxon signed-rank tests; p<0.05). RESULTS: While histological observations provided evidence of new bone formation at the vicinity of both Ti and Mg, the bone marrow at distance from the implant-interface featured morphological differences between groups (Fig. 2). At 3 days, the proportion of the interstitial and microvascular area was significantly higher at the expense of the area occupied by the hematopoietic cells in Mg- vs Ti-implanted metaphyses. At 28 days, bone marrow around Mg implants showed significantly higher adiposity in comparison to Ti implants. Yet, no differences in the trabecular bone micro-architecture were detected between biomaterials by micro-CT analysis at distance from the implant-interface. The RNA extracted from cells from the implant surface and from the peri-implant bone revealed good quality, allowing detailed molecular analysis. CONCLUSIONS: In comparison to non-degradable Ti controls, the degradation of Mg implants changes the composition of the peri-implant bone marrow, but yet without alteration of new bone formation at the implant interface. ACKNOWLEDGEMENTS: Mg rods were generously provided by the Helmholtz-Zentrum Hereon, Geesthacht, Germany. This project is part of the European Training Network within the framework of Horizon 2020 Marie Skłodowska-Curie Action No 811226.
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| 2. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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Dissecting the sequential interaction between biodegradable magnesium implants and soft tissues in vivo
- 2022
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Ingår i: Materials Science and Engineering Congress, Dredsen, Germany, 27-29 September 2022.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Magnesium-based biomaterials are developed with the intention to enable tissue regeneration while being degraded under physiological conditions and eventually eliminated from the body. Once in contact with tissues, the biodegradability and the biocompatibility of magnesium implants (Mg) are governed by the direct interactions with their immediate milieu. The precise mechanisms through which the soft tissue micro-environment shapes the behaviour of Mg and the host-response remain elusive. Here, it is demonstrated that Mg degradation modulates the initial acute immune response and the subsequent fibrous encapsulation upon subcutaneous implantation in rats monitored at 1-, 3-, 6-, 14- and 28-days following surgery. In comparison to titanium implants (Ti), the initial profuse release of Mg degradation products activates pro-inflammatory pathways through increased recruitment of inflammatory cells to the soft tissue/implant interface and upregulation of pro-inflammatory genes, in parallel with a superior neo-angiogenesis and vascularization at Mg. After 6d, a shift in Mg degradation kinetics dissipates the initial pro-inflammatory response and facilitates the assembly of a comparatively thinner fibrous tissue capsule than around Ti. The reduction in the fibrous encapsulation around the Mg implant aligns with a superior expression of anti-fibrotic marker FOXO-1 at the tissue interface with Mg versus Ti. Mg induce an initial potent yet transient inflammatory response, which is associated with less adverse fibrous encapsulation after tissue healing. Tailoring Mg with controlled initial degradation appears to be crucial to enabling a successful coupling between inflammation and tissue repair during the early host response to Mg.
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| 3. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues
- 2023
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Ingår i: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 26, s. 353-369
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Tidskriftsartikel (refereegranskat)abstract
- Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.
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