Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair
Abstract
1. Introduction
2. Materials and Methods
2.1. Expansion of Pre-Osteoblast MC3T3-E1 and Osteoclast Progenitors RAW 264.7 Cells
2.2. Optimisation of Mg2+ Concentrations for MC3T3-E1 and RAW 264.7 Cells Culture
Cell Proliferation and Metabolic Activity
2.3. Effects of Magnesium on Osteogenesis
2.3.1. ALP Activity and Staining
2.3.2. Assessment of Mg2+ Matrix Mineralisation
2.3.3. Gene Expression of Osteoblast Markers
2.4. Assessment of Mg2+ on Osteoclast Differentiation
2.4.1. Effects of Mg2+ Concentration on Osteoclast Markers Expression
2.4.2. Effect of Mg2+ in RANKL-Derived Osteoclast Fusion
2.4.3. Tartrate Resistant Acid Phosphatase (TRAP) Staining and Activity
2.4.4. F-Actin Fluorescence Staining
2.5. Scaffold Fabrication and Characterisation
2.5.1. nHA-Mg Particles Synthesis
2.5.2. Scaffolds Fabrication
2.5.3. Scaffolds Physicochemical Characterisation
2.6. 3D Cell Culture
2.6.1. Cell Proliferation
2.6.2. Gene Expression
2.6.3. Calcium Quantification
2.6.4. TRAP Activity
3. Results
3.1. Effect of Mg2+ on Pre-Osteoblast and Pre-Osteoclast Cell Viability
3.2. Effect of Mg2+ Increasing Concentration in Osteoblasts Gene Expression, ALP Activity, and Matrix Mineralisation
3.3. Effect of Mg2+ Concentration on Osteoclast Markers Expression and Maturation
3.4. Characterisation of the Composition and Mechanical Properties of Mg2+-Loaded Collagen-nHA Scaffolds
3.5. Effect of Mg2+-Containing Scaffolds on Pre-Osteoblast and Pre-Osteoclast Cell Viability and Differentiation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Bartl, R.; Bartl, C. Modelling and Remodelling of Bone. In Bone Disorders: Biology, Diagnosis, Prevention, Therapy; Bartl, R., Bartl, C., Eds.; Springer International Publishing: Cham, Switzerland, 2017; pp. 21–30. ISBN 978-3-319-29182-6. [Google Scholar]
- Tatsumi, S.; Ishii, K.; Amizuka, N.; Li, M.; Kobayashi, T.; Kohno, K.; Ito, M.; Takeshita, S.; Ikeda, K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007, 5, 464–475. [Google Scholar] [CrossRef]
- Cho, H.; Lee, J.; Jang, S.; Lee, J.; Oh, T.I.; Son, Y.; Lee, E. CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment. Int. J. Mol. Sci. 2020, 22, 325. [Google Scholar] [CrossRef] [PubMed]
- González-Vázquez, A.; Planell, J.A.; Engel, E. Extracellular calcium and CaSR drive osteoinduction in mesenchymal stromal cells. Acta Biomater. 2014, 10, 2824–2833. [Google Scholar] [CrossRef] [PubMed]
- Groenendijk, I.; van Delft, M.; Versloot, P.; van Loon, L.J.C.; de Groot, L.C.P.G.M. Impact of magnesium on bone health in older adults: A systematic review and meta-analysis. Bone 2022, 154, 116233. [Google Scholar] [CrossRef] [PubMed]
- Rondanelli, M.; Faliva, M.A.; Tartara, A.; Gasparri, C.; Perna, S.; Infantino, V.; Riva, A.; Petrangolini, G.; Peroni, G. An update on magnesium and bone health. Biometals 2021, 34, 715–736. [Google Scholar] [CrossRef]
- Qiao, W.; Wong, K.H.M.; Shen, J.; Wang, W.; Wu, J.; Li, J.; Lin, Z.; Chen, Z.; Matinlinna, J.P.; Zheng, Y.; et al. TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration. Nat. Commun. 2021, 12, 2885. [Google Scholar] [CrossRef]
- Zhou, H.; Liang, B.; Jiang, H.; Deng, Z.; Yu, K. Magnesium-based biomaterials as emerging agents for bone repair and regeneration: From mechanism to application. J. Magnes. Alloys 2021, 9, 779–804. [Google Scholar] [CrossRef]
- Zhang, Y.; Xu, J.; Ruan, Y.C.; Yu, M.K.; O’Laughlin, M.; Wise, H.; Chen, D.; Tian, L.; Shi, D.; Wang, J.; et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat. Med. 2016, 22, 1160–1169. [Google Scholar] [CrossRef]
- O’Neill, E.; Awale, G.; Daneshmandi, L.; Umerah, O.; Lo, K.W.-H. The roles of ions on bone regeneration. Drug Discov. Today 2018, 23, 879–890. [Google Scholar] [CrossRef]
- Wu, J.; Cheng, X.; Wu, J.; Chen, J.; Pei, X. The development of magnesium-based biomaterials in bone tissue engineering: A review. J. Biomed. Mater. Res. Part B Appl. Biomater. 2024, 112, e35326. [Google Scholar] [CrossRef]
- Roohaniesfahani, I.; Wang, J.; No, Y.J.; de Candia, C.; Miao, X.; Lu, Z.; Shi, J.; Kaplan, D.L.; Jiang, X.; Zreiqat, H. Modulatory effect of simultaneously released magnesium, strontium, and silicon ions on injectable silk hydrogels for bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2019, 94, 976–987. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.-J.; El-Fiqi, A.; Kim, H.-W. Synergetic Cues of Bioactive Nanoparticles and Nanofibrous Structure in Bone Scaffolds to Stimulate Osteogenesis and Angiogenesis. ACS Appl. Mater. Interfaces 2017, 9, 2059–2073. [Google Scholar] [CrossRef]
- Kazakova, G.; Safronova, T.; Golubchikov, D.; Shevtsova, O.; Rau, J.V. Resorbable Mg2+-Containing Phosphates for Bone Tissue Repair. Materials 2021, 14, 4857. [Google Scholar] [CrossRef] [PubMed]
- Górnicki, T.; Lambrinow, J.; Golkar-Narenji, A.; Data, K.; Domagała, D.; Niebora, J.; Farzaneh, M.; Mozdziak, P.; Zabel, M.; Antosik, P.; et al. Biomimetic Scaffolds—A Novel Approach to Three Dimensional Cell Culture Techniques for Potential Implementation in Tissue Engineering. Nanomaterials 2024, 14, 531. [Google Scholar] [CrossRef]
- Molino, G.; Palmieri, M.C.; Montalbano, G.; Fiorilli, S.; Vitale-Brovarone, C. Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: A short review. Biomed. Mater. 2020, 15, 022001. [Google Scholar] [CrossRef]
- Burr, D.B.; Allen, M.R. (Eds.) Basic and Applied Bone Biology; Elsevier Science: Amsterdam, The Netherlands, 2013; ISBN 978-0-12-416015-6. [Google Scholar]
- Chang, J.; Zhang, X.; Dai, K. Bioactive Materials for Bone Regeneration; Academic Press: New York, NY, USA, 2020; ISBN 978-0-12-813504-4. [Google Scholar]
- Georgeanu, V.A.; Gingu, O.; Antoniac, I.V.; Manolea, H.O. Current Options and Future Perspectives on Bone Graft and Biomaterials Substitutes for Bone Repair, from Clinical Needs to Advanced Biomaterials Research. Appl. Sci. 2023, 13, 8471. [Google Scholar] [CrossRef]
- Zhu, P.; Masuda, Y.; Koumoto, K. The effect of surface charge on hydroxyapatite nucleation. Biomaterials 2004, 25, 3915–3921. [Google Scholar] [CrossRef]
- Liu, Y.; Luo, D.; Yu, M.; Wang, Y.; Jin, S.; Li, Z.; Cui, S.; He, D.; Zhang, T.; Wang, T.; et al. Thermodynamically Controlled Self-Assembly of Hierarchically Staggered Architecture as an Osteoinductive Alternative to Bone Autografts. Adv. Funct. Mater. 2019, 29, 1806445. [Google Scholar] [CrossRef]
- Huang, G.; Li, F.; Zhao, X.; Ma, Y.; Li, Y.; Lin, M.; Jin, G.; Lu, T.J.; Genin, G.M.; Xu, F. Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment. Chem. Rev. 2017, 117, 12764–12850. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Mcadams II, D.A.; Grunlan, J.C. Nano/Micro-Manufacturing of Bioinspired Materials: A Review of Methods to Mimic Natural Structures. Adv. Mater. 2016, 28, 6292–6321. [Google Scholar] [CrossRef] [PubMed]
- Zhu, L.; Luo, D.; Liu, Y. Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration. Int. J. Oral Sci. 2020, 12, 6. [Google Scholar] [CrossRef]
- Sevari, S.P.; Kim, J.K.; Chen, C.; Nasajpour, A.; Wang, C.-Y.; Krebsbach, P.H.; Khademhosseini, A.; Ansari, S.; Weiss, P.S.; Moshaverinia, A. Whitlockite-Enabled Hydrogel for Craniofacial Bone Regeneration. ACS Appl. Mater. Interfaces 2021, 13, 35342–35355. [Google Scholar] [CrossRef]
- Young, S.; Patel, Z.S.; Kretlow, J.D.; Murphy, M.B.; Mountziaris, P.M.; Baggett, L.S.; Ueda, H.; Tabata, Y.; Jansen, J.A.; Wong, M.; et al. Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model. Tissue Eng. Part A 2009, 15, 2347–2362. [Google Scholar] [CrossRef]
- Maistrovskaia, Y.V.; Nevzorova, V.A.; Ugay, L.G.; Gnedenkov, S.V.; Kotsurbei, E.A.; Moltyh, E.A.; Kostiv, R.E.; Sinebryukhov, S.L. Bone Tissue Condition during Osteosynthesis of a Femoral Shaft Fracture Using Biodegradable Magnesium Implants with an Anticorrosive Coating in Rats with Experimental Osteoporosis. Appl. Sci. 2022, 12, 4617. [Google Scholar] [CrossRef]
- Li, G.; Zhang, L.; Wang, L.; Yuan, G.; Dai, K.; Pei, J.; Hao, Y. Dual modulation of bone formation and resorption with zoledronic acid-loaded biodegradable magnesium alloy implants improves osteoporotic fracture healing: An in vitro and in vivo study. Acta Biomater. 2018, 65, 486–500. [Google Scholar] [CrossRef] [PubMed]
- Lin, S.; Yang, G.; Jiang, F.; Zhou, M.; Yin, S.; Tang, Y.; Tang, T.; Zhang, Z.; Zhang, W.; Jiang, X. A Magnesium-Enriched 3D Culture System that Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration. Adv. Sci. 2019, 6, 1900209. [Google Scholar] [CrossRef]
- Amerstorfer, F.; Fischerauer, S.F.; Fischer, L.; Eichler, J.; Draxler, J.; Zitek, A.; Meischel, M.; Martinelli, E.; Kraus, T.; Hann, S.; et al. Long-term in vivo degradation behavior and near-implant distribution of resorbed elements for magnesium alloys WZ21 and ZX50. Acta Biomater. 2016, 42, 440–450. [Google Scholar] [CrossRef]
- Izumiya, M.; Haniu, M.; Ueda, K.; Ishida, H.; Ma, C.; Ideta, H.; Sobajima, A.; Ueshiba, K.; Uemura, T.; Saito, N.; et al. Evaluation of MC3T3-E1 Cell Osteogenesis in Different Cell Culture Media. Int. J. Mol. Sci. 2021, 22, 7752. [Google Scholar] [CrossRef] [PubMed]
- Hwang, P.W.; Horton, J.A. Variable osteogenic performance of MC3T3-E1 subclones impacts their utility as models of osteoblast biology. Sci. Rep. 2019, 9, 8299. [Google Scholar] [CrossRef]
- Mira-Pascual, L.; Tran, A.N.; Andersson, G.; Näreoja, T.; Lång, P. A Sub-Clone of RAW264.7-Cells Form Osteoclast-Like Cells Capable of Bone Resorption Faster than Parental RAW264.7 through Increased De Novo Expression and Nuclear Translocation of NFATc1. Int. J. Mol. Sci. 2020, 21, 538. [Google Scholar] [CrossRef]
- ISO 10993-5:2009; Biological Evaluation of Medical Devices. Part 5: Tests for In Vitro Cytotoxicity. ISO: Geneva, Switzerland, 2009.
- Stipniece, L.; Salma-Ancane, K.; Borodajenko, N.; Sokolova, M.; Jakovlevs, D.; Berzina-Cimdina, L. Characterization of Mg-substituted hydroxyapatite synthesized by wet chemical method. Ceram. Int. 2014, 40, 3261–3267. [Google Scholar] [CrossRef]
- Cunniffe, G.M.; O’Brien, F.J.; Partap, S.; Levingstone, T.J.; Stanton, K.T.; Dickson, G.R. The synthesis and characterization of nanophase hydroxyapatite using a novel dispersant-aided precipitation method. J. Biomed. Mater. Res. Part A 2010, 95, 1142–1149. [Google Scholar] [CrossRef]
- Cunniffe, G.M.; Dickson, G.R.; Partap, S.; Stanton, K.T.; O’Brien, F.J. Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J. Mater. Sci. Mater. Med. 2010, 21, 2293–2298. [Google Scholar] [CrossRef] [PubMed]
- Cunniffe, G.M.; Curtin, C.M.; Thompson, E.M.; Dickson, G.R.; O’Brien, F.J. Content-Dependent Osteogenic Response of Nanohydroxyapatite: An in Vitro and in Vivo Assessment within Collagen-Based Scaffolds. ACS Appl. Mater. Interfaces 2016, 8, 23477–23488. [Google Scholar] [CrossRef]
- Haugh, M.G.; Jaasma, M.J.; O’Brien, F.J. The effect of dehydrothermal treatment on the mechanical and structural properties of collagen-GAG scaffolds. J. Biomed. Mater. Res. Part A 2009, 89, 363–369. [Google Scholar] [CrossRef] [PubMed]
- Murphy, C.M.; Matsiko, A.; Haugh, M.G.; Gleeson, J.P.; O’Brien, F.J. Mesenchymal stem cell fate is regulated by the composition and mechanical properties of collagen-glycosaminoglycan scaffolds. J. Mech. Behav. Biomed. Mater. 2012, 11, 53–62. [Google Scholar] [CrossRef] [PubMed]
- Haugh, M.G.; Murphy, C.M.; McKiernan, R.C.; Altenbuchner, C.; O’Brien, F.J. Crosslinking and mechanical properties significantly influence cell attachment, proliferation, and migration within collagen glycosaminoglycan scaffolds. Tissue Eng. Part A 2011, 17, 1201–1208. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Chen, Q.; Mao, X. Magnesium Enhances Osteogenesis of BMSCs by Tuning Osteoimmunomodulation. BioMed Res. Int. 2019, 2019, 7908205. [Google Scholar] [CrossRef]
- Wang, J.; Witte, F.; Xi, T.; Zheng, Y.; Yang, K.; Yang, Y.; Zhao, D.; Meng, J.; Li, Y.; Li, W.; et al. Recommendation for modifying current cytotoxicity testing standards for biodegradable magnesium-based materials. Acta Biomater. 2015, 21, 237–249. [Google Scholar] [CrossRef]
- Yoshizawa, S.; Brown, A.; Barchowsky, A.; Sfeir, C. Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater. 2014, 10, 2834–2842. [Google Scholar] [CrossRef]
- Liu, W.; Guo, S.; Tang, Z.; Wei, X.; Gao, P.; Wang, N.; Li, X.; Guo, Z. Magnesium promotes bone formation and angiogenesis by enhancing MC3T3-E1 secretion of PDGF-BB. Biochem. Biophys. Res. Commun. 2020, 528, 664–670. [Google Scholar] [CrossRef]
- Nie, X.; Sun, X.; Wang, C.; Yang, J. Effect of magnesium ions/Type I collagen promote the biological behavior of osteoblasts and its mechanism. Regen. Biomater. 2020, 7, 53–61. [Google Scholar] [CrossRef]
- Luthringer, B.J.C.; Willumeit-Römer, R. Effects of magnesium degradation products on mesenchymal stem cell fate and osteoblastogenesis. Gene 2016, 575, 9–20. [Google Scholar] [CrossRef]
- Wang, J.; Ma, X.-Y.; Feng, Y.-F.; Ma, Z.-S.; Ma, T.-C.; Zhang, Y.; Li, X.; Wang, L.; Lei, W. Magnesium Ions Promote the Biological Behaviour of Rat Calvarial Osteoblasts by Activating the PI3K/Akt Signalling Pathway. Biol. Trace Elem. Res. 2017, 179, 284–293. [Google Scholar] [CrossRef] [PubMed]
- Leidi, M.; Dellera, F.; Mariotti, M.; Maier, J.A.M. High magnesium inhibits human osteoblast differentiation in vitro. Magnes. Res. 2011, 24, 1–6. [Google Scholar] [CrossRef]
- Zhang, L.; Yang, C.; Li, J.; Zhu, Y.; Zhang, X. High extracellular magnesium inhibits mineralized matrix deposition and modulates intracellular calcium signaling in human bone marrow-derived mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2014, 450, 1390–1395. [Google Scholar] [CrossRef] [PubMed]
- Fernandes, H.; Dechering, K.; Van Someren, E.; Steeghs, I.; Apotheker, M.; Leusink, A.; Bank, R.; Janeczek, K.; Van Blitterswijk, C.; de Boer, J. The Role of Collagen Crosslinking in Differentiation of Human Mesenchymal Stem Cells and MC3T3-E1 Cells. Tissue Eng. Part A 2009, 15, 3857–3867. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Feyerabend, F.; Schilling, A.F.; Willumeit-Römer, R.; Luthringer, B.J.C. Effects of extracellular magnesium extract on the proliferation and differentiation of human osteoblasts and osteoclasts in coculture. Acta Biomater. 2015, 27, 294–304. [Google Scholar] [CrossRef]
- Belluci, M.M.; Schoenmaker, T.; Rossa-Junior, C.; Orrico, S.R.; de Vries, T.J.; Everts, V. Magnesium deficiency results in an increased formation of osteoclasts. J. Nutr. Biochem. 2013, 24, 1488–1498. [Google Scholar] [CrossRef]
- Wu, L.; Luthringer, B.J.C.; Feyerabend, F.; Schilling, A.F.; Willumeit, R. Effects of extracellular magnesium on the differentiation and function of human osteoclasts. Acta Biomater. 2014, 10, 2843–2854. [Google Scholar] [CrossRef]
- Zhai, Z.; Qu, X.; Li, H.; Yang, K.; Wan, P.; Tan, L.; Ouyang, Z.; Liu, X.; Tian, B.; Xiao, F.; et al. The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-κB and NFATc1 signaling. Biomaterials 2014, 35, 6299–6310. [Google Scholar] [CrossRef]
- Murphy, C.M.; Duffy, G.P.; Schindeler, A.; O’brien, F.J. Effect of collagen-glycosaminoglycan scaffold pore size on matrix mineralization and cellular behavior in different cell types. J. Biomed. Mater. Res. Part A 2016, 104, 291–304. [Google Scholar] [CrossRef]
- Murphy, C.M.; Schindeler, A.; Gleeson, J.P.; Yu, N.Y.C.; Cantrill, L.C.; Mikulec, K.; Peacock, L.; O’Brien, F.J.; Little, D.G. A collagen–hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates. Acta Biomater. 2014, 10, 2250–2258. [Google Scholar] [CrossRef]
- Kaur, K.; Sannoufi, R.; Butler, J.S.; Murphy, C.M. Biomimetic Inspired Hydrogels for Regenerative Vertebral Body Stenting. Curr. Osteoporos. Rep. 2023, 21, 806–814. [Google Scholar] [CrossRef] [PubMed]
- Kaur, K.; Falgous, L.; Kamal, N.; Caffrey, D.; Cavanagh, B.L.; Koc-Bilican, B.; Kaya, M.; Shvets, I.; Curtin, C.M.; Murphy, C.M. Mesoporous Biosilica Beads for Controlled Selenium Nanoparticle Delivery from Collagen-Chitosan Scaffolds: Promoting Bone Formation and Suppressing Prostate Cancer Growth. Adv. NanoBiomed Res. 2024, 4, 2400110. [Google Scholar] [CrossRef]
- Zhao, R.; Meng, X.; Pan, Z.; Li, Y.; Qian, H.; Zhu, X.; Yang, X.; Zhang, X. Advancements in nanohydroxyapatite: Synthesis, biomedical applications and composite developments. Regen. Biomater. 2024, 12, rbae129. [Google Scholar] [CrossRef] [PubMed]
- Hayrapetyan, A.; Bongio, M.; Leeuwenburgh, S.C.G.; Jansen, J.A.; van den Beucken, J.J.J.P. Effect of Nano-HA/Collagen Composite Hydrogels on Osteogenic Behavior of Mesenchymal Stromal Cells. Stem Cell Rev. Rep. 2016, 12, 352–364. [Google Scholar] [CrossRef]
- Tajvar, S.; Hadjizadeh, A.; Samandari, S.S. Scaffold degradation in bone tissue engineering: An overview. Int. Biodeterior. Biodegrad. 2023, 180, 105599. [Google Scholar] [CrossRef]
- Antoniac, I.V.; Antoniac, A.; Vasile, E.; Tecu, C.; Fosca, M.; Yankova, V.G.; Rau, J.V. In vitro characterization of novel nanostructured collagen-hydroxyapatite composite scaffolds doped with magnesium with improved biodegradation rate for hard tissue regeneration. Bioact. Mater. 2021, 6, 3383–3395. [Google Scholar] [CrossRef]
- Sartori, M.; Pagani, S.; Ferrari, A.; Costa, V.; Carina, V.; Figallo, E.; Maltarello, M.C.; Martini, L.; Fini, M.; Giavaresi, G. A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations. Mater. Sci. Eng. C 2017, 70, 101–111. [Google Scholar] [CrossRef]
- Kim, K.-J.; Choi, S.; Cho, Y.S.; Yang, S.-J.; Cho, Y.-S.; Kim, K.K. Magnesium ions enhance infiltration of osteoblasts in scaffolds via increasing cell motility. J. Mater. Sci. Mater. Med. 2017, 28, 96. [Google Scholar] [CrossRef] [PubMed]
- Minardi, S.; Corradetti, B.; Taraballi, F.; Sandri, M.; Van Eps, J.; Cabrera, F.J.; Weiner, B.K.; Tampieri, A.; Tasciotti, E. Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation. Biomaterials 2015, 62, 128–137. [Google Scholar] [CrossRef]
- Calabrese, G.; Giuffrida, R.; Fabbi, C.; Figallo, E.; Furno, D.L.; Gulino, R.; Colarossi, C.; Fullone, F.; Giuffrida, R.; Parenti, R.; et al. Collagen-Hydroxyapatite Scaffolds Induce Human Adipose Derived Stem Cells Osteogenic Differentiation In Vitro. PLoS ONE 2016, 11, e0151181. [Google Scholar] [CrossRef]
- Nie, X.; Shi, Y.; Wang, L.; Abudureheman, W.; Yang, J.; Lin, C. Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair. Heliyon 2024, 10, e30279. [Google Scholar] [CrossRef]
- Liu, C.; Ma, N.; Sun, C.; Shen, X.; Li, J.; Wang, C. The effect of magnesium ions synergistic with mineralized collagen on osteogenesis/angiogenesis properties by modulating macrophage polarization in vitro and in vivo. Biomed. Mater. 2024, 19, 035028. [Google Scholar] [CrossRef]
- Menale, C.; Campodoni, E.; Palagano, E.; Mantero, S.; Erreni, M.; Inforzato, A.; Fontana, E.; Schena, F.; van’t Hof, R.; Sandri, M.; et al. Mesenchymal Stromal Cell-Seeded Biomimetic Scaffolds as a Factory of Soluble RANKL in Rankl-Deficient Osteopetrosis. Stem Cells Transl. Med. 2018, 8, 22–34. [Google Scholar] [CrossRef]
- Müller, E.; Schoberwalter, T.; Mader, K.; Seitz, J.-M.; Kopp, A.; Baranowsky, A.; Keller, J. The Biological Effects of Magnesium-Based Implants on the Skeleton and Their Clinical Implications in Orthopedic Trauma Surgery. Biomater. Res. 2024, 28, 0122. [Google Scholar] [CrossRef] [PubMed]
- Li, R.W.; Kirkland, N.T.; Truong, J.; Wang, J.; Smith, P.N.; Birbilis, N.; Nisbet, D.R. The influence of biodegradable magnesium alloys on the osteogenic differentiation of human mesenchymal stem cells. J. Biomed. Mater. Res. Part A 2014, 102, 4346–4357. [Google Scholar] [CrossRef] [PubMed]
Sample | MgCl2 (M) | Ca(NO3)2·4H2O (M) | (NH4)2)HPO4 (M) | Mg/(Mg + Ca) mol (%) | (Mg + Ca)/P Ratio |
---|---|---|---|---|---|
nHA | – | 1 | 0.6 | 0 | 1.67 |
10 Mg/nHA | 0.1 | 0.9 | 0.6 | 10 | 1.67 |
25 Mg/nHA | 0.25 | 0.75 | 0.6 | 25 | 1.67 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Paiva, S.S.; Ferreira, A.; Pakenham, E.; Kaur, K.; Cavanagh, B.; O’Brien, F.J.; Murphy, C.M. Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair. J. Funct. Biomater. 2025, 16, 363. https://doi.org/10.3390/jfb16100363
Paiva SS, Ferreira A, Pakenham E, Kaur K, Cavanagh B, O’Brien FJ, Murphy CM. Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair. Journal of Functional Biomaterials. 2025; 16(10):363. https://doi.org/10.3390/jfb16100363
Chicago/Turabian StylePaiva, Sílvia Sá, Avelino Ferreira, Eavan Pakenham, Kulwinder Kaur, Brenton Cavanagh, Fergal J. O’Brien, and Ciara M. Murphy. 2025. "Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair" Journal of Functional Biomaterials 16, no. 10: 363. https://doi.org/10.3390/jfb16100363
APA StylePaiva, S. S., Ferreira, A., Pakenham, E., Kaur, K., Cavanagh, B., O’Brien, F. J., & Murphy, C. M. (2025). Magnesium Ion-Mediated Regulation of Osteogenesis and Osteoclastogenesis in 2D Culture and 3D Collagen/Nano-Hydroxyapatite Scaffolds for Enhanced Bone Repair. Journal of Functional Biomaterials, 16(10), 363. https://doi.org/10.3390/jfb16100363