Re-establishment of macrophage homeostasis by titanium surface modification in type II diabetes promotes osseous healing

Lee, Ryan S. B.; Hamlet, Stephen; Moon, Hojin; Ivanovski, Sašo

doi:10.1016/j.biomaterials.2020.120464

Cited by 49 publications

(38 citation statements)

References 54 publications

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“…Several mechanisms are known to contribute to osteoblastic differentiation . Prior studies suggested that M2 macrophage polarization may contribute to osteoblastic differentiation and bone mineralization. , Macrophages have two subphenotypes, and the polarization state of macrophages is dependent on factors in the microenvironment, including several cytokines and chemokines . Mechanistically, M2 macrophages secrete osteogenic factors that stimulate the differentiation and activation of MSCs and subsequently increase bone mineralization.…”

Section: Resultsmentioning

confidence: 99%

Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing

Zhou

Lin

Xiong

et al. 2021

ACS Appl. Mater. Interfaces

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The immune system and skeletal system are closely linked. Macrophages are one of the most important immune cells for bone remodeling, playing a prohealing role mainly through M2 phenotype polarization. Baicalein (5,6,7-trihydroxyflavone, BCL) has been well documented to have a noticeable promotion effect on M2 macrophage polarization. However, due to the limitations in targeted delivery to macrophages and the toxic effect on other organs, BCL has rarely been used in the treatment of bone fractures. In this study, we developed mesoporous silica and Fe3O4 composite-targeted nanoparticles loaded with BCL (BCL@MMSNPs-SS-CD-NW), which could be magnetically delivered to the fracture site. This induced macrophage recruitment in a targeted manner, polarizing them toward the M2 phenotype, which was demonstrated to induce mesenchymal stem cells (MSCs) toward osteoblastic differentiation. The mesoporous silicon nanoparticles (MSNs) were prepared with surface sulfhydrylation and amination modification, and the mesoporous channels were blocked with β-cyclodextrin. The outer layer of the mesoporous silicon was added with an amantane-modified NW-targeting peptide to obtain the targeted nanosystem. After entering macrophages, BCL could be released from nanoparticles since the disulfide linker could be cleaved by intracellular glutathione (GSH), resulting in the removal of cyclodextrin (CD) gatekeeper, which is a key element in the pro-bone-remodeling functions such as anti-inflammation and induction of M2 macrophage polarization to facilitate osteogenic differentiation. This nanosystem passively accumulated in the fracture site, promoting osteogenic differentiation activities, highlighting a potent therapeutic benefit with high biosafety.

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Section: Resultsmentioning

confidence: 99%

Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing

Zhou

Lin

Xiong

et al. 2021

ACS Appl. Mater. Interfaces

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“…125 The coating was found to mediate in vitro communication between co-cultured rat ASCs and human umbilical vein endothelial cells (HUVECs) through cellmatrix interactions that enhanced their paracrine effects (Figure 11A). When grown in co-culture in the presence of the multilayer coating, both ASCs and HUVECs increased their transmigration, as 36 well as gene or protein expression of angiogenic factors such as SDF-1 and VEGF, compared to cells grown on tissue culture plastic or uncoated Ti. There was some evidence of bone formation when Ti samples with the multilayer coating were implanted into rats subcutaneously or in the femur, but the process of in vivo osseointegration requires further investigation.…”

Section: Layer By Layer Self-assemblymentioning

confidence: 98%

“…SLA-treated Ti surfaces have also been studied in the context of certain diseases or conditions. For instance, Lee et al 36 produced hydrophilic nanostructured Ti surfaces by modifying with SLA and then storing in the absence of air induce spontaneous formation of surface features (Figure 6). This surface was found to promote osseous healing under type II diabetic conditions.…”

Section: Sandblasting and Acid Etching (Sla)mentioning

confidence: 99%

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Advances in implant surface modifications to improve osseointegration

Zhu

Wang

2021

Mater. Adv.

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“…Several mechanisms are known to contribute to osteoblastic differentiation [30]. Prior studies suggested that M2 macrophage polarization may contribute to osteoblastic differentiation and bone mineralization [31,32]. Macrophages have two sub-phenotypes, and the polarization state of macrophages is dependent on factors in the microenvironment including several cytokines and chemokines [33].…”

Section: M2 Macrophage Polarization Induces Mscs Towards Osteoblasitc Differentiation In Vitromentioning

confidence: 99%

Magnetically-Targeted Nanoparticle-Guided M2 Macrophage Polarization For Fracture Healing Promotion

Zhou

Lin

Xiong

et al. 2021

Preprint

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Background: Macrophages are essential for fracture healing, acting mainly through remodeling of the extracellular matrix and promotion of angiogenesis. The role of macrophages in regulating osteogenic differentiation, particularly that of the M2 phenotype, is increasingly researched. Baicalein (BCL) had also been shown to have pro-fracture-healing effects.Results: In this study, we developed mesoporous silica and Fe3O4 composite-targeted nanoparticles loaded with BCL (BCL@MMSNPs-SS-CD-NW), that could be magnetically delivered to the fracture site. These induced macrophage recruitment in a targeted manner, polarizing them towards the M2 phenotype, and thereby inducing MSCs towards osteoblastic differentiation. The mesoporous silicon nanoparticles (MSNs) were prepared with surface sulfhydrylation and amination modification, and the mesoporous channels were blocked with β-cyclodextrin. The outer layer of the mesoporous silicon was added with an amantane-modified NW targeting peptide to obtain the targeted nano-system. After entering macrophages, BCL could be released from nanoparticles since the disulfide linker could be cleaved by intracellular glutathione (GSH) resulting in the removing of CD gatekeeper, which is a key element in the pro-bone-remodeling functions, such as anti-inflammation and induction of M2 macrophage polarization to facilitate osteogenic differentiation.Conclusions: This nano-system passively accumulated in the fracture site, promoting osteogenic differentiation activities, highlighting a potent therapeutic benefit with high biosafety.

show abstract

Re-establishment of macrophage homeostasis by titanium surface modification in type II diabetes promotes osseous healing

Cited by 49 publications

References 54 publications

Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing

Dual-Targeted Nanoplatform Regulating the Bone Immune Microenvironment Enhances Fracture Healing

Advances in implant surface modifications to improve osseointegration

Magnetically-Targeted Nanoparticle-Guided M2 Macrophage Polarization For Fracture Healing Promotion

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