Injectable PLGA microspheres with tunable magnesium ion release for promoting bone regeneration

2019 ◽  
Vol 85 ◽  
pp. 294-309 ◽  
Author(s):  
Zuoying Yuan ◽  
Pengfei Wei ◽  
Yiqian Huang ◽  
Wenxin Zhang ◽  
Fuyu Chen ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Magnesium Ion ◽  
Plga Microspheres ◽  
Ion Release

scholarly journals Effective Actions of Ion Release from Mesoporous Bioactive Glass and Macrophage Mediators on the Differentiation of Osteoprogenitor and Endothelial Progenitor Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1152
Author(s):  
Alberto Polo-Montalvo ◽  
Laura Casarrubios ◽  
María Concepción Serrano ◽  
Adrián Sanvicente ◽  
María José Feito ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mesoporous Structure ◽  
Ion Release ◽  
Endothelial Progenitor ◽  
Matrix Mineralization ◽  
Intracellular Content

Due to their specific mesoporous structure and large surface area, mesoporous bioactive glasses (MBGs) possess both drug-delivery ability and effective ionic release to promote bone regeneration by stimulating osteogenesis and angiogenesis. Macrophages secrete mediators that can affect both processes, depending on their phenotype. In this work, the action of ion release from MBG-75S, with a molar composition of 75SiO2-20CaO-5P2O5, on osteogenesis and angiogenesis and the modulatory role of macrophages have been assessed in vitro with MC3T3-E1 pre-osteoblasts and endothelial progenitor cells (EPCs) in monoculture and in coculture with RAW 264.7 macrophages. Ca2+, phosphorous, and silicon ions released from MBG-75S were measured in the culture medium during both differentiation processes. Alkaline phosphatase activity and matrix mineralization were quantified as the key markers of osteogenic differentiation in MC3T3-E1 cells. The expression of CD31, CD34, VEGFR2, eNOS, and vWF was evaluated to characterize the EPC differentiation into mature endothelial cells. Other cellular parameters analyzed included the cell size and complexity, intracellular calcium, and intracellular content of the reactive oxygen species. The results obtained indicate that the ions released by MBG-75S promote osteogenesis and angiogenesis in vitro, evidencing a macrophage inhibitory role in these processes and demonstrating the high potential of MBG-75S for the preparation of implants for bone regeneration.

scholarly journals TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

2020 ◽  
Author(s):  
Wei Qiao ◽  
Karen H.M. Wong ◽  
Jie Shen ◽  
Wenhao Wang ◽  
Jun Wu ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Healing ◽  
Bone Repair ◽  
Transient Receptor Potential ◽  
Nuclear Accumulation ◽  
Magnesium Ion ◽  
Dependent Manner ◽  
Immune Microenvironment ◽  
Complex Biological Process ◽  
Macrophage Lineage

AbstractThe use of magnesium ion (Mg2+)-modified biomaterials in bone regeneration is a promising and cost-effective therapeutic. Despite the widespread observation on the osteogenic effects of Mg2+, the diverse roles played by Mg2+ in the complex biological process of bone healing have not been systematically dissected. Here, we reveal a previously unknown biphasic mode of action of Mg2+ in bone repair. In the early inflammation phase, Mg2+ primarily targets the monocyte-macrophage lineage to promote their recruitment, activation, and polarization. We showed that an increase in extracellular Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7) and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines like IL-8, leading to the formation of a pro-osteogenic immune microenvironment. In the later active repair/remodeling phase of bone healing, however, continued exposure of Mg2+ and IL-8 leads to over activation of NF-κB signaling in macrophages, turning the immune microenvironment into pro-osteoclastogenesis. Moreover, the presence of Mg2+ at this stage also decelerates bone maturation through the suppression of hydroxyapatite precipitation. The negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+, as we found prolonged delivery of Mg2+ compromises overall bone formation. Taken together, this study establishes a paradigm shift in understanding the diverse and multifaceted roles of Mg2+ in bone healing.

scholarly journals Effect of strontium doping on the biocompatibility of calcium phosphate-coated titanium substrates

2019 ◽  
Vol 17 (1) ◽  
pp. 228080001982651 ◽  
Author(s):  
Thuy-Duong Thi Nguyen ◽  
Yong-Seok Jang ◽  
Min-Ho Lee ◽  
Tae-Sung Bae
Keyword(s):  
Calcium Phosphate ◽  
Bone Regeneration ◽  
Molar Ratio ◽  
Calcium Phosphate Coating ◽  
Phosphate Coating ◽  
Biomedical Devices ◽  
Ion Release ◽  
Anodized Titanium ◽  
Strontium Doping

Background: Titanium biomedical devices coated with strontium-doped calcium phosphate ceramics can support desirable bone regeneration through anabolic and anti-catabolic effects of strontium and the compositions close to that of natural mineral tissue. Methods: Strontium was doped into the calcium phosphate coating using the cyclic pre-calcification method on the anodized titanium plate. The effects of the different concentration of strontium in treatment solution and cycle numbers of the pre-calcification treatment on the biocompatibility were investigated in terms of the changes in morphology and chemical composition of coating, ion release pattern and cytocompatibility in vitro. Results: At a high substitution ratio of strontium in the calcium phosphate coating, the size of precipitated particles was decreased and the solubility of the coating was increased. ASH55 group, which was coated by pre-calcification treatment of 20 cycles in coating solution with Sr:Ca molar ratio of 5:5, exhibited superior cellular attachment at 1 day and proliferation after 7 days of culturing in comparison with the non-doped surface and other doped surfaces. Conclusion: Sufficient strontium doping concentrations in calcium phosphate coating can enhance cell adhesion and proliferation on the titanium biomedical devices for bone regeneration.

Biological Activity of rhBMP-2 Released From PLGA Microspheres

2000 ◽  
Vol 122 (3) ◽  
pp. 289-292 ◽  
Author(s):  
J. B. Oldham, ◽  
L. Lu, ◽  
X. Zhu, and ◽  
B. D. Porter ◽  
T. E. Hefferan ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Body Fluids ◽  
Bone Morphogenetic Protein 2 ◽  
In Vitro Tests ◽  
Plga Microspheres ◽  
Skeletal Tissue ◽  
Morphogenetic Protein ◽  
Biodegradable Poly ◽  
Simulated Body Fluids

Human recombinant bone morphogenetic protein-2 (rhBMP-2) has been proven effective in stimulating the regeneration of bone in both skeletal and extraskeletal locations. Through encapsulation within, and release from, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) microspheres, a proven vehicle for sustained delivery of various proteins, the local concentrations of rhBMP-2 could be maintained at optimal levels to stimulate bone regeneration and remodeling at the site of healing in diverse clinical settings. Thus the purpose of this work was to investigate the encapsulation of rhBMP-2 in PLGA microspheres and its biologic activity upon release. Using in vitro tests in simulated body fluids, the effect of rhBMP-2 released from PLGA microspheres upon osteoblast cell cultures was found to be statistically similar to the effect produced by positive controls consisting of nonencapsulated aqueous rhBMP-2 in simulated body fluids. This clarifies an important step in skeletal tissue engineering strategies aimed at the use of encapsulated rhBMP-2 to stimulate bone regeneration and remodeling. [S0148-0731(00)01303-0]

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