The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration

Zhang, Wenjie; Wang, Guocheng; Liu, Yan; Zhao, Xiaobing; Zou, Duohong; Zhu, Chao; Jin, Yuqing; Huang, Qiyu; Sun, Jian; Liu, Xuanyong; Jiang, Xinquan; Zreiqat, Hala

doi:10.1016/j.biomaterials.2013.01.008

Cited by 287 publications

(250 citation statements)

References 40 publications

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“…33 Briefly, rats were injected intraperitoneally with 30 mg/kg Alizarin Red S (Sigma-Aldrich Co.) and 20 mg/kg calcein (Sigma-Aldrich Co.) at 2 and 6 weeks after implantation, respectively.…”

Section: Sequential Fluorescent Labelingmentioning

confidence: 99%

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Zhang¹,

Yu²,

Wang³

et al. 2018

IJN

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Introduction To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2) are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods A new growth factor delivery system was fabricated using BMP-2-loaded TiO 2 nanotubes by lyophilization with trehalose (TiO 2 -Lyo-Tre-BMP-2). We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT), sequential fluorescent labelling, and histological analysis. Results Compared with absorbed BMP-2-loaded TiO 2 nanotubes (TiO 2 -BMP-2), TiO 2 -Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO 2 -Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO 2 -BMP-2 nanotubes. Conclusion Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects.

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Section: Sequential Fluorescent Labelingmentioning

confidence: 99%

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Zhang¹,

Yu²,

Wang³

et al. 2018

IJN

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“…11 Taking into account the importance of both microtopographical and nanotopographical features, the synergistic effects of dual-length scale materials show promise for improving osseointegration. 12 In a previous study, a hierarchical hybrid micro/nanotip film was fabricated on a titanium surface (NT) using acid etching to form micropits; a sodium titanate nanotip texture was produced using hydrothermal treatment, and H + was then incorporated using an ion exchange process. The optimized NT surfaces showed better bioactivity and osteogenic activity compared with microrough titanium surfaces treated by acid etching alone.…”

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confidence: 99%

Magnesium ion implantation on a micro/nanostructured titanium surface promotes its bioactivity and osteogenic differentiation function

Wang¹,

Li²,

Zhang³

et al. 2014

IJN

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As one of the important ions associated with bone osseointegration, magnesium was incorporated into a micro/nanostructured titanium surface using a magnesium plasma immersion ion-implantation method. Hierarchical hybrid micro/nanostructured titanium surfaces followed by magnesium ion implantation for 30 minutes (Mg30) and hierarchical hybrid micro/nanostructured titanium surfaces followed by magnesium ion implantation for 60 minutes (Mg60) were used as test groups. The surface morphology, chemical properties, and amount of magnesium ions released were evaluated by field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, field-emission transmission electron microscopy, and inductively coupled plasma-optical emission spectrometry. Rat bone marrow mesenchymal stem cells (rBMMSCs) were used to evaluate cell responses, including proliferation, spreading, and osteogenic differentiation on the surface of the material or in their medium extraction. Greater increases in the spreading and proliferation ability of rBMMSCs were observed on the surfaces of magnesium-implanted micro/nanostructures compared with the control plates. Furthermore, the osteocalcin ( OCN ), osteopontin ( OPN ), and alkaline phosphatase ( ALP ) genes were upregulated on both surfaces and in their medium extractions. The enhanced cell responses were correlated with increasing concentrations of magnesium ions, indicating that the osteoblastic differentiation of rBMMSCs was stimulated through the magnesium ion function. The magnesium ion-implanted micro/nanostructured titanium surfaces could enhance the proliferation, spreading, and osteogenic differentiation activity of rBMMSCs, suggesting they have potential application in improving bone-titanium integration.

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“…Although the mechanisms behind metal ion-induced bone regeneration are not well understood (reviewed in [43]), the presence of ions probably affects macrophages. Zirconia (in baghdadite) has been shown to be pro-inflammatory [44], whereas strontium and zinc (in Sr-HT-gahnite) have been shown to affect bone remodelling [45,46] and promote anti-inflammatory activity [47]. Future studies are focused on determining whether the presence of these ions contributed to the differential activation of macrophages observed in this work.…”

Section: Discussionmentioning

confidence: 82%

In vitroresponse of macrophages to ceramic scaffolds used for bone regeneration

Graney

Roohani‐Esfahani

Zreiqat

et al. 2016

J. R. Soc. Interface.

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Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocytederived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo. Specifically, baghdadite (Ca 3 ZrSi 2 O 9 ) and strontium-hardystonite-gahnite (Sr-Ca 2 ZnSi 2 O 7 -ZnAl 2 O 4 ) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate-hydroxyapatite (TCP-HA). Principal component analysis revealed that the scaffolds differentially regulated macrophage phenotype. Temporal changes in gene expression included shifts in markers of pro-inflammatory M1, anti-inflammatory M2a and pro-remodelling M2c macrophage phenotypes. Of note, TCP-HA scaffolds promoted upregulation of many M1-related genes and downregulation of many M2a-and M2c-related genes. Effects of the scaffolds on macrophages were attributed primarily to direct cell-scaffold interactions because of only minor changes observed in transwell culture. Ultimately, elucidating macrophage-biomaterial interactions will facilitate the design of immunomodulatory biomaterials for bone repair.

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The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration

Cited by 287 publications

References 40 publications

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Magnesium ion implantation on a micro/nanostructured titanium surface promotes its bioactivity and osteogenic differentiation function

In vitroresponse of macrophages to ceramic scaffolds used for bone regeneration

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