Abstract
Mimicking compositional and constructional features of the extracellular matrix (ECM) is an effective parameter in improving the biological response of biomaterials. In this regard, carbon nanotube (CNT) and gelatin were added to magnesium-calcium phosphate cement (CNG) to mimic fibrillar construction and organic composition of ECM, respectively, besides the CNG performance was compared with the plain and CNT-reinforced cement. Cementation behavior of the cements was investigated by evaluating their setting time, cement composition variation during setting, and viscosity fluctuation. Furthermore, compressive strength, degradation, and cell response of the cements were compared. Adding 5 wt.% gelatin reduced setting time about 60%, because of gel formation, not due to struvite precipitation. Moreover, the gelatin decreased compressive strength by about 20%. Although gelatin decreased compressive strength, the strength remained in the range attributed to trabecular bone. All the types of cement indicated shear thinning behavior that made their injectability feasible. Compared to other types of cement, CNG enhanced proliferation and differentiation of mesenchymal stem cells besides faster degradation, nontoxicity and suitable cell adhesion. Hence, mimicking features of CNG enhanced osteoconductivity and osteoinductivity of the cement compared to the plain one.
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References
Stevens M M. Biomaterials for bone tissue engineering. Materials Today, 2008, 11, 18–25.
Wegst U G K, Bai H, Saiz E, Tomsia A P, Ritchie R O. Bioinspired structural materials. Nature Materials, 2015, 14, 23–36.
Shekaran A, García A J. Extracellular matrix-mimetic adhesive biomaterials for bone repair. Journal of Biomedical Materials Research Part A, 2011, 96 A, 261–272.
Freshney R I. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th ed., John Wiley & Sons, Inc., Hoboken, New Jersey, 2010, 33.
Karp G. Cell and Molecular Biology: Concepts and Experiments, 7th ed., John Wiley & Sons, Inc., Hoboken, New Jersey, 2013, 236.
Rezaie H R, Esnaashary M H, Karfarma M, Öchsner A. Bone Cement: From Simple Cement Concepts to Complex Biomimetic Design, Springer, Cham, Switzerland, 2020, 84.
Esnaashary M H, Fathi M H, Ahmadian M. The effect of the two-step sintering process on consolidation of fluoridated hydroxyapatite and its mechanical properties and bioactivity. International Journal of Applied Ceramic Technology, 2014, 11, 47–56.
Esnaashary M H, Fathi M H, Ahmadian M. In vitro evaluation of human osteoblast-like cell proliferation and attachment on nanostructured fluoridated hydroxyapatite. Biotechnology Letters, 2014, 36, 1343–1347.
Ginebra M P, Fernández E, De Maeyer E A, Verbeeck R M, Boltong M G, Ginebra J, Driessens F C, Planell J A. Setting reaction and hardening of an apatitic calcium phosphate cement. Journal of Dental Research, 1997, 76, 905–912.
Tamimi F, Sheikh Z, Barralet J. Dicalcium phosphate cements: Brushite and monetite. Acta Biomaterialia, 2012, 8, 474–487.
Grossardt C, Ewald A, Grover L M, Barralet J E, Gbureck U. Passive and active in vitro resorption of calcium and magnesium phosphate cements by osteoclastic cells. Tissue Engineering Part A, 2010, 16, 3687–3695.
Ewald A, Helmschrott K, Knebl G, Mehrban N, Grover L M, Gbureck U. Effect of cold-setting calcium- and magnesium phosphate matrices on protein expression in osteoblastic cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2011, 96 B, 326–332.
Ostrowski N, Roy A, Kumta P N. Magnesium phosphate cement systems for hard tissue applications: A review. ACS Biomaterials Science & Engineering, 2016, 2, 1067–1083.
Klammert U, Reuther T, Blank M, Reske I, Barralet J E, Grover L M, Kübler A C, Gbureck U. Phase composition, mechanical performance and in vitro biocompatibility of hydraulic setting calcium magnesium phosphate cement. Acta Biomaterialia, 2010, 6, 1529–1535.
Vorndran E, Ewald A, Müller F A, Zorn K, Kufner A, Gbureck U. Formation and properties of magnesium-ammonium-phosphate hexahydrate biocements in the Ca-Mg-PO4 system. Journal of Materials Science: Materials in Medicine, 2011, 22, 429–436.
Wu F, Wei J, Guo H, Chen F P, Hong H, Liu C S. Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration. Acta Biomaterialia, 2008, 4, 1873–1884.
Brückner T, Hurle K, Stengele A, Groll J, Gbureck U. Mechanical activation and cement formation of trimagnesium phosphate. Journal of the American Ceramic Society, 2018, 24, 4123–4131.
Ostrowski N, Sharma V, Roy A, Kumta P N. Systematic assessment of synthesized tri-magnesium phosphate powders (amorphous, semi-crystalline and crystalline) and cements for ceramic bone cement applications. Journal of Materials Science & Technology, 2015, 31, 437–444.
Pina S, Olhero S M, Gheduzzi S, Miles A W, Ferreira J M F. Influence of setting liquid composition and liquid-to-powder ratio on properties of a Mg-substituted calcium phosphate cement. Acta Biomaterialia, 2009, 5, 1233–1240.
Karfarma M, Esnaashary M H, Rezaie H R, Javadpour J. Poly(propylene fumarate)/magnesium calcium phosphate injectable bone composite: Effect of filler size and its weight fraction on mechanical properties. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 2019, 233, 1165–1174.
Babaie E, Lin B, Bhaduri S B. A new method to produce macroporous Mg-phosphate bone growth substitutes. Materials Science and Engineering C, 2017, 75, 602–609.
Moseke C, Saratsis V, Gbureck U. Injectability and mechanical properties of magnesium phosphate cements. Journal of Materials Science: Materials in Medicine, 2011, 22, 2591–2598.
Mestres G, Abdolhosseini M, Bowles W, Huang S H, Aparicio C, Gorr S U, Ginebra M P. Antimicrobial properties and dentin bonding strength of magnesium phosphate cements. Acta Biomaterialia, 2013, 9, 8384–8393.
Klammert U, Ignatius A, Wolfram U, Reuther T, Gbureck U. In vivo degradation of low temperature calcium and magnesium phosphate ceramics in a heterotopic model. Acta Biomaterialia, 2011, 7, 3469–3475.
Yu Y L, Wang J, Liu C S, Zhang B, Chen H H, Guo H, Zhong G, Qu W D, Jiang S H, Huang H G. Evaluation of inherent toxicology and biocompatibility of magnesium phosphate bone cement. Colloids and Surfaces B: Biointerfaces, 2010, 76, 496–504.
Newman P, Minett A, Ellis-Behnke R, Zreiqat H. Carbon nanotubes: Their potential and pitfalls for bone tissue regeneration and engineering. Nanomedicine, 2013, 9, 1139–1158.
Kotchey G P, Zhao Y, Kagan V E, Star A. Peroxidase-mediated biodegradation of carbon nanotubes in vitro and in vivo. Advanced Drug Delivery Reviews, 2013, 65, 1921–1932.
Poland C A, Duffin R, Kinloch I, Maynard A, Wallace W A H, Seaton A, Stone V, Brown S, Macnee W, Donaldson K. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nature Nanotechnology, 2008, 3, 423–428.
Kagan VE, Konduru N V, Feng W H, Allen B L, Conroy J, Volkov Y, Vlasova I I, Belikova N A, Yanamala N, Kapralov A, Tyurina Y Y, Shi J, Kisin E R, Murray A R, Franks J, Stolz D, Gou P P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova A A. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nature Nanotechnology, 2010, 5, 354–359.
Bhattacharya K, El-Sayed R, Andón F T, Mukherjee S P, Gregory J, Li H, Zhao Y C, Seo W, Fornara A, Brandner B, Toprak M S, Leifer K, Star A, Fadeel B. Lactoperoxidase-mediated degradation of single-walled carbon nanotubes in the presence of pulmonary surfactant. Carbon, 2015, 91, 506–517.
Chew K K, Low K L, Zein S H S, McPhail D S, Gerhardt L C, Roether J A, Boccaccini A R. Reinforcement of calcium phosphate cement with multi-walled carbon nanotubes and bovine serum albumin for injectable bone substitute applications. Journal of the Mechanical Behavior of Biomedical Materials, 2011, 4, 331–339.
Wang X P, Ye J D, Wang Y J, Chen L. Reinforcement of calcium phosphate cement by bio-mineralized carbon nanotube. Journal of the American Ceramic Society, 2007, 90, 962–964.
Echave M C, Burgo L S, Pedraz J L, Orive G. Gelatin as biomaterial for tissue engineering. Current Pharmaceutical Design, 2017, 23, 3567–3584.
Bigi A, Panzavolta S, Rubini K. Setting mechanism of a biomimetic bone cement. Chemistry of Materials, 2004, 16, 3740–3745.
Bigi A, Torricelli P, Fini M, Bracci B, Panzavolta S, Sturba L, Giardino R. A biomimetic gelatin-calcium phosphate bone cement. The International Journal of Artificial Organs, 2004, 27, 664–673.
Bigi A, Bracci B, Panzavolta S. Effect of added gelatin on the properties of calcium phosphate cement. Biomaterials, 2004, 25, 2893–2899.
Orshesh Z, Hesaraki S, Khanlarkhani A. Blooming gelatin: An individual additive for enhancing nanoapatite precipitation, physical properties, and osteoblastic responses of nanostructured macroporous calcium phosphate bone cements. International Journal of Nanomedicine, 2017, 12, 745–758.
Habraken W J E M, Boerman O C, Wolke J G C, Mikos A G, Jansen J A. In vitro growth factor release from injectable calcium phosphate cements containing gelatin microspheres. Journal of Biomedical Materials Research Part A, 2009, 91A, 614–622.
Perez RA, Del Valle S, Altankov G, Ginebra M P. Porous hydroxyapatite and gelatin/hydroxyapatite microspheres obtained by calcium phosphate cement emulsion. Journal of Biomedical Materials Research Part B: Applied Biomaterial, 2011, 97B, 156–166.
Alvarez Perez M A, Guarino V, Cirillo V, Ambrosio L. In vitro mineralization and bone osteogenesis in poly(ε-caprolactone)/ gelatin nanofibers. Journal of Biomedical Materials Research Part A, 2012, 100 A, 3008–3019.
Esnaashary M H, Rezaie H R, Khavandi A, Javadpour J. Solubility controlling of the precursor powders of magnesium phosphate cement by changing the powder composition. Advances in Applied Ceramics, 2017, 116, 286–292.
Esnaashary M H, Rezaie H R, Khavandi A, Javadpour J. Evaluation of setting time and compressive strength of a new bone cement precursor powder containing Mg-Na-Ca. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 2018, 232, 1017–1024.
Esnaashary M H, Khavandi A, Rezaie H R, Javadpour J. Mg-P/c-SWCNT Bone Cement: The effect of filler on setting behavior, compressive strength and biocompatibility. Journal of Bionic Engineering, 2020, 17, 100–112.
Lutterotti L. Total pattern fitting for the combined size-strain-stress-texture determination in thin film diffraction. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2010, 268, 334–340.
Russell D W, Sambrook J. Molecular Cloning: A Laboratory Manual, 3rd ed., Cold Spring Harbor Laboratory Press, New York, United States, 2001, A1–7.
Bullard J W, Jennings H M, Livingston R A, Nonat A, Scherer G W, Schweitzer J S, Scrivener K L, Thomas J J. Mechanisms of cement hydration. Cement and Concrete Research, 2011, 41, 1208–1223.
Espanol M, Perez R A, Montufar E B, Marichal C, Sacco A, Ginebra M P. Intrinsic porosity of calcium phosphate cements and its significance for drug delivery and tissue engineering applications. Acta Biomaterialia, 2009, 5, 2752–2762.
Low K L, Tan S H, Zein S H S, Roether J A, Mouriño V, Boccaccini A R. Calcium phosphate-based composites as injectable bone substitute materials. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2010, 94, 273–286.
Wagoner Johnson A J, Herschler A B. A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. Acta Biomaterialia, 2011, 7, 16–30.
Ewald A, Helmschrott K, Knebl G, Mehrban N, Grover L M, Gbureck U. Effect of cold-setting calcium- and magnesium phosphate matrices on protein expression in osteoblastic cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2011, 96, 326–332.
Chen F P, Liu C S, Wei J, Chen X L. Physicochemical properties and biocompatibility of white dextrin modified injectable calcium-magnesium phosphate cement. International Journal of Applied Ceramic Technology, 2012, 9, 979–990.
Motameni A, Alshemary A Z, Dalgic A D, Keskin D, Evis Z. Lanthanum doped dicalcium phosphate bone cements for potential use as filler for bone defects. Materials Today Communications, 2020, 26, 101774.
Nadiv R, Vasilyev G, Shtein M, Peled A, Zussman E, Regev O. The multiple roles of a dispersant in nanocomposite systems. Composites Science and Technology, 2016, 133, 192–199.
Miller M A, Race A, Gupta S, Higham P, Clarke M T, Mann K A. The role of cement viscosity on cement-bone apposition and strength. Journal of arthroplasty, 2007, 22, 109–116.
Krause W R, Miller J, Ng P. The viscosity of acrylic bone cements. Journal of Biomedical Materials Research Part A, 1982, 16, 219–243.
Zhou H, Agarwal A K, Goel V K, Bhaduri S B. Microwave assisted preparation of magnesium phosphate cement (MPC) for orthopedic applications: A novel solution to the exothermicity problem. Materials Science and Engineering C: Materials for Biological Applications, 2013, 33, 4288–4294.
Murphy-Ullrich J E. The de-adhesive activity of matricellular proteins: Is intermediate cell adhesion an adaptive state? Journal of Clinical Investigation, 2001, 107, 785–790.
Zhang J, Ma X Y, Lin D, Shi H S, Yuan Y, Tang W, Zhou H J, Guo H, Qian J C, Liu C S. Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism. Biomaterials, 2015, 53, 251–264.
Zreiqat H, Howlett C R, Zannettino A, Evans P, Schulze-Tanzil G, Knabe C, Shakibaei M. Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants. Journal of Biomedical Materials Research Part A, 2002, 62, 175–184.
Kroustalli A A, Kourkouli S N, Deligianni D D. Cellular function and adhesion mechanisms of human bone marrow mesenchymal stem cells on multi-walled carbon nanotubes. Annals of Biomedical Engineering, 2013, 41, 2655–2665.
Lee H H, Shin U S, Won J E, Kim H. Preparation of hydroxyapatite-carbon nanotube composite nanopowders. Materials Letters, 2011, 65, 208–211.
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Esnaashary, M.H., Karfarma, M., Rezaie, H.R. et al. The Comparative Study of Gelatin/CNT-contained Mg-Ca-P Bone Cement with the Plain and CNT-reinforced Ones. J Bionic Eng 18, 623–636 (2021). https://doi.org/10.1007/s42235-021-0048-5
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DOI: https://doi.org/10.1007/s42235-021-0048-5