Inflammatory response to magnesium-based biodegradable implant materials

Costantino, Maria Domenica; Schuster, A.; Helmholz, Heike; Meyer-Rachner, A.; Willumeit‐Römer, Regine; Luthringer-Feyerabend, Bérengère

doi:10.1016/j.actbio.2019.10.014

Cited by 98 publications

(69 citation statements)

References 46 publications

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“…On the contrary, the bare Mg alloy induced the secretion of almost similar levels of IL-1β and of higher amounts of TNF-α than TCPS sample but at the same time exhibited the highest multinuclear index. Constantino et al [158] investigated the in vivo effect of various Mg extracts on cytokine production and reported an increased level of IL-1β at 24 and 72 h, thus indicating that Mg based biomaterials are capable of influencing macrophage-cells activity at a molecular level. More recently it has been demonstrated, in a mouse tibial fracture model, that the expression pattern of TNF-α and IL-1β, following bone injury, has two peaks: the first peak emerges within the first 24 h and lasts for almost 72 h, while the second peak occurs after 3-4 weeks [155].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Negrescu

Necula

Gebaur

et al. 2021

IJMS

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Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflection Fourier-transform infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that AZ31 alloy was perfectly coated with the PCL fibers loaded with CM and ZnO, which had an important influence on tuning the release of the active ingredient. Furthermore, in terms of degradation in phosphate-buffered saline (PBS) solution, the PCL-ZnO- and secondary PCL-CM-ZnO-coated samples exhibited the best corrosion behaviour. The in vitro results showed the PCL-CM-ZnO and, to a lower extent, PCL-ZnO coated sample exhibited the best behaviour in terms of inflammatory response and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated differentiation of RAW 264.7 macrophages into osteoclasts. Altogether, the results obtained suggest that the coating of Mg alloys with fibrous PCL containing CM and/or ZnO can constitute a feasible strategy for biomedical applications.

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Section: Discussionmentioning

confidence: 99%

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Negrescu

Necula

Gebaur

et al. 2021

IJMS

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“…The M2 macrophages promote tissue healing and the production of IL-10 and TGF-β 40 . There are several reports of magnesium effect on inflammation 6,41 and the response to biomaterials 7,[42][43][44] by the regulation of macrophage polarization . In this study, culturing the cells on the Mg-doped sol-gel materials caused a significant decrease in TNF-α secretion.…”

Section: Discussionmentioning

confidence: 99%

Characterization of magnesium doped sol-gel biomaterial for bone tissue regeneration: The effect of Mg ion in protein adsorption

Cerqueira

Romero‐Gavilán

García‐Arnáez

et al. 2021

Materials Science and Engineering: C

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Magnesium is the fourth most abundant element in the human body with a wide battery of functions in the maintenance of normal cell homeostasis. In the bone, this element incorporates in the hydroxyapatite structure and it takes part in mineral metabolism and regulates osteoclast functions. In this study, sol-gel materials with increasing concentrations of MgCl2 (0.5, 1, and 1.5%) were synthesized and applied onto Ti surfaces as coatings. The materials were first physicochemically characterized. In vitro responses were examined using the MC3T3-E1 osteoblastic cells and RAW264.7 macrophages. Human serum protein adsorption was evaluated employing nLC-MS/MS. The incorporation of Mg did not affect the crosslinking of the sol-gel network, and a controlled release of Mg was observed; it was not cytotoxic at any of the tested concentrations. The cytoskeleton arrangement of MC3T3-E1 cells cultured on the Mg-doped materials changed in comparison with controls; the cells became more elongated, with protruded lamellipodia and increased cell surface. The expression of integrins (ITGA5 and ITGB1) was boosted by Mg-coatings. The ALP activity and expression of TGF-β, OSX and RUNX2 genes were also increased. In RAW264.7 cells, TNF-α secretion was reduced, while TGF-β and IL-4 expression rose. These changes correlated with the altered protein adsorption patterns. The Mg-doped coatings showed increased adsorption of anti-inflammatory (CLUS, IC1, CFAH, and VTNC), cell adhesion (DSG1, FILA2, and DESP) and tissue regeneration (VTNC and CYTA) proteins. This integrated approach to biomaterial characterization revealed the potential of Mg in bone tissue regeneration.

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“…Reducing the host responses through modulating macrophage polarization has been the focus of many recent studies. 18 , 21 – 24 In addition, the monocyte-macrophage cell lineage is known as a key player in bone regeneration and acute inflammatory response. This is largely owing to their high plasticity in response to environmental signals and their multiple roles in bone homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“… 30 However, as above-mentioned, immune cells, especially macrophages also play key roles in directing the host responses to biomaterials and we should study their responses to ZX alloys. To address this point, Costantino et al 23 studied the in vitro effects of Mg-based alloys and their degradation products on macrophage polarization, and observed that the alloys could stimulate the expression of both pro- and anti-inflammatory factors. Although it is undeniable that the biomaterial’s behavior in the body could be different to the in vitro conditions, in vivo studies on the early inflammatory and bone tissue responses to Mg-based alloys are still lacking in the literature.…”

Section: Introductionmentioning

confidence: 99%

Early osteoimmunomodulatory effects of magnesium–calcium–zinc alloys

et al. 2021

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Today, substantial attention is given to biomaterial strategies for bone regeneration, and among them, there is a growing interest in using immunomodulatory biomaterials. The ability of a biomaterial to induce neo vascularization and macrophage polarization is a major factor in defining its success. Magnesium (Mg)-based degradable alloys have attracted significant attention for bone regeneration owing to their biodegradability and potential for avoiding secondary removal surgeries. However, there is insufficient evidence in the literature regarding the early inflammatory responses to these alloys in vivo. In this study, we investigated the early body responses to Mg-0.45wt%Zn-0.45wt%Ca pin-shaped alloy (known as ZX00 alloy) in rat femora 2, 5, and 10 days after implantation. We used 3D micro computed tomography (µCT), histological, immunohistochemical, histomorphometrical, and small angle X-ray scattering (SAXS) analyses to study new bone formation, early macrophage polarization, neo vascularization, and bone quality at the implant bone interface. The expression of macrophage type 2 biological markers increased significantly after 10 days of Mg alloy implantation, indicating its potential in stimulating macrophage polarization. Our biomineralization results using µCT as well as histological stained sections did not indicate any statistically significant differences between different time points for both groups. The activity of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx 2) biological markers decreased significantly for Mg group, indicating less osteoblast activity. Generally, our results supported the potential of ZX00 alloy to enhance the expression of macrophage polarization in vivo; however, we could not observe any statistically significant changes regarding biomineralization.

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Inflammatory response to magnesium-based biodegradable implant materials

Cited by 98 publications

References 46 publications

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Characterization of magnesium doped sol-gel biomaterial for bone tissue regeneration: The effect of Mg ion in protein adsorption

Early osteoimmunomodulatory effects of magnesium–calcium–zinc alloys

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