Magnesium ions enhance infiltration of osteoblasts in scaffolds via increasing cell motility

Magnesium (Mg) ions are the most abundant intracellular divalent cations and play a pivotal role in numerous cellular processes. Biodegradable Mg-containing materials, including scaffolds, are promising candidates for orthopedic applications. Here, we investigated the effect of Mg ions on the cellular properties of osteoblasts. Cytotoxicity tests on osteoblasts confirmed that no cytotoxic effects were found up to a supplementing Mg ion concentration of 10 mM. Mg ions at a concentration of 5 mM increased the migration and invasiveness of osteoblasts. To investigate the stimulatory effect of Mg ions on cell motility in scaffolds, we fabricated 10 wt% Mg ion-containing polycaprolactone (PCL) scaffolds, using the wire-network molding (WNM) technique. Mg ion-containing scaffolds persistently released Mg ions at a concentration of 5 mM in the media after pre-incubation. Furthermore, increased cell motility was confirmed in Mg ion-containing scaffolds by quantification of genomic DNA and protein content. Our results provide an important basis for the function of Mg ions and their effect on cell motility, and propose a novel role for Mg ions in scaffold applications.Graphical Abstract

[1]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[2]  Koichi Matsuo,et al.  Osteoclast-osteoblast communication. , 2008, Archives of biochemistry and biophysics.

[3]  M. Karsdal,et al.  Local communication on and within bone controls bone remodeling. , 2009, Bone.

[4]  J. Lee,et al.  Fabrication of dual-pore scaffolds using SLUP (salt leaching using powder) and WNM (wire-network molding) techniques. , 2014, Materials science & engineering. C, Materials for biological applications.

[5]  J. Kanczler,et al.  Osteogenesis and angiogenesis: the potential for engineering bone. , 2008, European cells & materials.

[6]  D. Bernardini,et al.  High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro. , 2004, Biochimica et biophysica acta.

[7]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[8]  J. Nellesen,et al.  Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. , 2010, Acta biomaterialia.

[9]  N. Kuboyama,et al.  A biodegradable porous composite scaffold of PGA/beta-TCP for bone tissue engineering. , 2010, Bone.

[10]  C. Sfeir,et al.  Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. , 2014, Acta biomaterialia.

[11]  P. Cerri,et al.  Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells , 2015, BioMed research international.

[12]  Yi Tang,et al.  TGF-β1-induced Migration of Bone Mesenchymal Stem Cells Couples Bone Resorption and Formation , 2009, Nature Medicine.

[13]  C. Sfeir,et al.  Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction. , 2015, Acta biomaterialia.

[14]  N. Sims,et al.  Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption. , 2008, Seminars in cell & developmental biology.

[15]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[16]  F. Wittea,et al.  In vivo corrosion of four magnesium alloys and the associated bone response , 2004 .

[17]  Ana Rita Costa-Pinto,et al.  Scaffolds based bone tissue engineering: the role of chitosan. , 2011, Tissue engineering. Part B, Reviews.

[18]  J. Vormann Magnesium: nutrition and metabolism. , 2003, Molecular aspects of medicine.

[19]  Young-Sam Cho,et al.  The fabrication of well-interconnected polycaprolactone/hydroxyapatite composite scaffolds, enhancing the exposure of hydroxyapatite using the wire-network molding technique. , 2017, Journal of biomedical materials research. Part B, Applied biomaterials.

[20]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[21]  B. Liu,et al.  Effect of magnesium ion on human osteoblast activity , 2016, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[22]  F. Wolf,et al.  Cell (patho)physiology of magnesium. , 2008, Clinical science.

[23]  A. Romani Magnesium in health and disease. , 2013, Metal ions in life sciences.

[24]  Xiaoling Zhang,et al.  Effects of magnesium alloys extracts on adult human bone marrow-derived stromal cell viability and osteogenic differentiation , 2010, Biomedical materials.

[25]  T. Martin,et al.  Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. , 2014, BoneKEy reports.

[26]  T. Martin,et al.  Osteoclast-derived activity in the coupling of bone formation to resorption. , 2005, Trends in molecular medicine.