Tuning the surface potential to reprogram immune microenvironment for bone regeneration

Li, Mei; Chu, Xiao; Wang, Donghui; Jian, Linjia; Liu, Lidan; Yao, Mengyu; Zhang, Dongdong; Zheng, Yufeng; Liu, Xuanyong; Zhang, Yu; Peng, Feng

doi:10.1016/j.biomaterials.2022.121408

Cited by 39 publications

(32 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that metformin facilitated M2 macrophages, we therefore concluded that interventions promoting M2 polarization boosted osteogenesis. The PI3K/AKT/mTOR pathway is a key link between inflammation and bone formation [ 31 , 32 ]. We focused on the expression levels of p-PI3K, p-AKT, and p-mTOR by western blot, and they were markedly increased after coculture with metformin-treated M2 macrophages ( Figure 6(c) ).…”

Section: Resultsmentioning

confidence: 99%

Metformin Facilitates Osteoblastic Differentiation and M2 Macrophage Polarization by PI3K/AKT/mTOR Pathway in Human Umbilical Cord Mesenchymal Stem Cells

Shen

Jin

et al. 2022

Stem Cells International

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are the most promising multipotent stem cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. This cellular flexibility contributes to widespread clinical use of MSCs in tissue repair and regeneration. The immune system is a key player in regulating bone remodeling. In recent years, the association between the immune system and bone metabolism has become an increasing focus of interest. Metformin, a glucose-lowering drug, exerts powerful impact on metabolic signaling. However, whether metformin can modulate bone metabolism or whether metformin can influence immune milieu by regulation of macrophages has not been thoroughly elucidated. Herein, we specifically explored the complex interactions between macrophages and human umbilical cord mesenchymal stem cells (UC-MSCs) in the context of metformin. Our research demonstrated that metformin not only stimulated osteogenesis of UC-MSCs but also influenced the immune system via promoting M2 but reducing M1 macrophages. Mechanically, we found that metformin-treated M2 macrophages possessed more potent osteoinductive capacity in our coculture system. Molecularly, these metformin-stimulated M2 macrophages facilitated osteogenesis via activating the PI3K/AKT/mTOR pathway. As demonstrated by using PI3K-specific inhibitor LY294002, we found that the pathway inhibitor partly reversed osteoinductive activity which was activated by coculture of metformin-treated M2 macrophages. Overall, our novel research illuminated the cooperative and synergistic effects of metformin and M2 macrophages on the dynamic balance of bone metabolism.

show abstract

Section: Resultsmentioning

confidence: 99%

Metformin Facilitates Osteoblastic Differentiation and M2 Macrophage Polarization by PI3K/AKT/mTOR Pathway in Human Umbilical Cord Mesenchymal Stem Cells

Shen

Jin

et al. 2022

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…C3H10T1/2 cells were purchased from the Type Culture Collection of the Chinese Academy of Sciences and cultured in Modified Eagle’s medium (MEM; Gibco, Waltham, MA, USA) containing 10% FBS, 2 mM L-glutamine (Sigma Aldrich, Missouri, MO, USA) and 1% sodium pyruvate (Leagene Biotechnology, Beijing, China). The conditions of the cell incubator were 37 °C, 5% CO 2 , and 95% humidity [ 23 ]. All the in vitro cell experiments were conducted using C3H10T1/2.…”

Section: Methodsmentioning

confidence: 99%

Oxyhydroxide-Coated PEO–Treated Mg Alloy for Enhanced Corrosion Resistance and Bone Regeneration

Xie

Cheng

Zhou

et al. 2022

JFB

Self Cite

View full text Add to dashboard Cite

Plasma electrolytic oxidation (PEO) is widely used as a surface modification method to enhance the corrosion resistance of Mg alloy, the most likely applied biodegradable material used in orthopedic implants. However, the pores and cracks easily formed on the PEO surface are unfavorable for long-term corrosion resistance. In this study, to solve this problem, we used simple immersion processes to construct Mn and Fe oxyhydroxide duplex layers on the PEO-treated AZ31 (PEO–Mn/Fe). As control groups, single Mn and Fe oxyhydroxide layers were also fabricated on PEO (denoted as PEO–Mn and PEO–Fe, respectively). PEO–Mn showed a similar porous morphology to the PEO sample. However, the PEO–Fe and PEO–Mn/Fe films completely sealed the pores on the PEO surfaces, and no cracks were observed even after the samples were immersed in water for 7 days. Compared with PEO, PEO–Mn, and PEO–Fe, PEO–Mn/Fe exhibited a significantly lower self-corrosion current, suggesting better corrosion resistance. In vitro C3H10T1/2 cell culture showed that PEO–Fe/Mn promoted the best cell growth, alkaline phosphatase activity, and bone-related gene expression. Furthermore, the rat femur implantation experiment showed that PEO–Fe/Mn–coated Mg showed the best bone regeneration and osteointegration abilities. Owing to enhanced corrosion resistance and osteogenesis, the PEO–Fe/Mn film on Mg alloy is promising for orthopedic applications.

show abstract

“…The morphology of the biomaterial-seeded cells can also be examined by scanning electron microscopy (SEM) [ 14 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ], as well as the intracellular structures by transmission electron microscopy (TEM) [ 65 , 68 ]. Cell morphology and distribution can also be assessed using immunofluorescence staining of actin filaments, by means of anti-phalloidin antibodies among others, which allows for the analysis of the cytoskeleton conformation of cell growth in contact with the biomaterials [ 14 , 52 , 54 , 55 , 57 , 60 , 62 , 64 , 65 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

Section: Biomaterials Biocompatibilitymentioning

confidence: 99%

“…A qualitative and quantitative measure of cell viability can be assessed with different alternative methods. Fluorescent live/dead assays are able to discriminate between live and dead cells by evaluating plasma membrane integrity and the activity of the esterase enzyme, both maintained only in viable cells [ 54 , 55 , 60 , 62 , 70 , 74 , 75 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Other commercial colorimetric assays for the evaluation of cell viability are available on the market and, among the most widely used are the cell counting kit-8 (CCK-8) assay that allows a sensitive colorimetric measure of viable cells, using a water-soluble tetrazolium salt that produces, in presence of active dehydrogenases in living cells, an orange formazan product, and the amount of formazan produced is directly proportional to the number of viable cells [ 55 , 57 , 58 , 62 , 73 , 76 , 80 , 81 , 85 , 86 , 87 , 88 , 89 ].…”

Section: Biomaterials Biocompatibilitymentioning

confidence: 99%

“…The expression of adhesion-related genes, namely integrin subunit alpha 5 ( ITGA5 ), integrin subunit beta 3 ( ITGB3 ), integrin subunit alpha V ( ITGAV ), integrin subunit beta 1 ( ITGB1 ), protein tyrosine kinase 2 ( PTK2/FAK ), and vinculin ( VCL ), can be analyzed after culturing cells on biomaterials [ 74 , 105 ]. The use of focal adhesion staining kits is also reported [ 106 ].…”

Section: Biomaterials Biocompatibilitymentioning

confidence: 99%

See 1 more Smart Citation

Translating Material Science into Bone Regenerative Medicine Applications: State-of-The Art Methods and Protocols

Pietro

Palmieri

Papi

et al. 2022

IJMS

View full text Add to dashboard Cite

In the last 20 years, bone regenerative research has experienced exponential growth thanks to the discovery of new nanomaterials and improved manufacturing technologies that have emerged in the biomedical field. This revolution demands standardization of methods employed for biomaterials characterization in order to achieve comparable, interoperable, and reproducible results. The exploited methods for characterization span from biophysics and biochemical techniques, including microscopy and spectroscopy, functional assays for biological properties, and molecular profiling. This review aims to provide scholars with a rapid handbook collecting multidisciplinary methods for bone substitute R&D and validation, getting sources from an up-to-date and comprehensive examination of the scientific landscape.

show abstract

Tuning the surface potential to reprogram immune microenvironment for bone regeneration

Cited by 39 publications

References 52 publications

Metformin Facilitates Osteoblastic Differentiation and M2 Macrophage Polarization by PI3K/AKT/mTOR Pathway in Human Umbilical Cord Mesenchymal Stem Cells

Metformin Facilitates Osteoblastic Differentiation and M2 Macrophage Polarization by PI3K/AKT/mTOR Pathway in Human Umbilical Cord Mesenchymal Stem Cells

Oxyhydroxide-Coated PEO–Treated Mg Alloy for Enhanced Corrosion Resistance and Bone Regeneration

Translating Material Science into Bone Regenerative Medicine Applications: State-of-The Art Methods and Protocols

Contact Info

Product

Resources

About