Preparation and characterization of injectable PMMA-strontium-substituted bioactive glass bone cement composites
I. Goñi
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorR. Rodríguez
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorI. García-Arnáez
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorJ. Parra
Unidad Asociada CAA-CSIC. Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Complejo Asistencial de Ávila. Hospital Provincial., 05071 Ávila, Spain
Search for more papers by this authorCorresponding Author
M. Gurruchaga
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Correspondence to: M. Gurruchaga; E-mail: [email protected]Search for more papers by this authorI. Goñi
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorR. Rodríguez
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorI. García-Arnáez
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Search for more papers by this authorJ. Parra
Unidad Asociada CAA-CSIC. Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Complejo Asistencial de Ávila. Hospital Provincial., 05071 Ávila, Spain
Search for more papers by this authorCorresponding Author
M. Gurruchaga
Department of Science and Technology of Polymers, POLYMAT (Institute of Polymeric Materials), Faculty of Chemistry, University of The Basque Country (UPV/EHU), P°Manuel de Lardizabal, 3., 20018 San Sebastián, Spain
Correspondence to: M. Gurruchaga; E-mail: [email protected]Search for more papers by this author†In memoriam of our dear colleague Prof. José Ignacio Eguiazabal, researcher and Director of Polymer Science and Technology Department (UPV-EHU).
This article was published online on 5 June 2017. An error was subsequently identified. This notice is included in the online version to indicate that has been corrected 12 June 2017.
Abstract
In most minimally-invasive procedures used to address severe pain arising from compression fractures of the vertebral bodies, such as percutaneous vertebroplasty (PVP), a poly(methyl methacrylate) (PMMA) bone cement is used. Shortcomings of this type of cement, such as high exotherm temperature and lack of bioactivity, are well known. We prepared different formulations of a composite bone cement, whose solid constituents consisted of PMMA beads and particles of a bioactive glass (BG), where 0–20%(w/w) of the calcium component was substituted by strontium. The difference between the formulations was in the relative amounts of the solid phase constituents and in the Sr-content of BG. We determined the influence of the mixture of solid phase constituents of the cement formulation on a collection of properties, such as maximum exotherm temperature (Tmax), setting time (tset), and injectability (I). The selection of the PMMA beads was crucial to obtain cement composite formulations capable to be efficiently injected. Results allowed to select nine solid phase mixtures to be further tested. Then, we determined the influence of the composition of these composite bone cements on Tmax, tset, I, and cell proliferation. The results showed that the performance of various of the selected composite cements was better than that of PMMA cement reference, with lower Tmax, lower tset, and higher I. We found that incorporation of Sr-substituted BGs into these materials bestows bioactivity properties associated with the role of Sr in bone formation, leading to some composite cement formulations that may be suitable for use in PVP. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1245–1257, 2018.
REFERENCES
- 1 Lewis G. Properties of nanofiller-loaded poly(methyl methacrylate) bone cement composites for orthopedic applications: A review. J Biomed Mater Res B 2016; 00B:000–000.
- 2 Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361: 569–579.
- 3 Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie 1987; 33: 166–168.
- 4 Mathis JM, Barr JD, Belkoff SM, Barr MS, Jensen ME, Deramond H. Percutaneous vertebroplasty: A developing standard of care for vertebral compression fractures. Am J Neuroradial 2001; 22: 373–381.
- 5 Weill A, Chiras J, Simon JM, Rose M, Sola-Martínez T, Enkaoua E. Spinal metastases: Indications for and results of percutaneous injection of acrylic surgical cement. Radiology 1996; 199: 241–247.
- 6 Yi X, Lu H, Tian F, et al. Recompression in new levels after percutaneous vertebroplasty and kyphoplasty compared with conservative treatment. Arch Orthop Traum Surg 2014; 134: 21–30.
- 7 Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009; 361: 557–568.
- 8 Robinson Y, Olerud C. Vertebroplasty and kyphoplasty—A systematic review of cement augmentation techniques for osteoporotic vertebral compression fractures compared to standard medical therapy. Maturitas 2012; 72: 42–49.
- 9 Lewis G. Injectable bone cements for use in vertebroplasty and kyphoplasty: State-of-the-art review. J Biomed Mater Res B Appl Biomater 2006; 76B: 456–468.
- 10 Widmer Soyka RP, Helgason B, Hazrati Marangalou J, van den Bergh JP, Rietbergen Ferguson SJ. The effectiveness of percutaneous vertebroplasty is determined by the patient-specific bone condition and the treatment strategy. PLoS ONE 2016; 11: e0151680.
- 11
Freeman MAR,
Brandley GW,
Ravell PA. Observation upon the interface between bone and PMMA cement. J Bone Jt Surg 1982; 64B: 489–493.
10.1302/0301-620X.64B4.7096429 Google Scholar
- 12 Shinzato S, Nakamura T, Ando K, Kokubo T, Kitamura Y. Mechanical properties and osteoconductivity of new bioactive composites consisting of partially crystallized glass beads and poly(methyl methacrylate). J Biomed Mater Res 2002; 60: 556–563.
- 13
Shinzato S,
Kobayashi M,
Mousa WF,
Kamimura M,
Neo M,
Kitamura Y,
Kokubo T,
Nakamura, T. Bioactive PMMA-based bone cement: Comparison of glass beads, apatite- and wollastonite-containing glass-ceramic, and hydroxyapatite fillers on mechanical and biological properties. J Biomed Mat Res 2000; 51: 258–272.
10.1002/(SICI)1097-4636(200008)51:2<258::AID-JBM15>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 14 Vargas Coronado R, Cervantes JM, Cauich Rodríguez JV, Vera Graciano R, Martínez Richa A. Estudio de las propiedades de cementos óseos preparados con metacrilatos funcionarizados e hidroxiapatita. Rev Mex Ing Biomed 2001; 22: 54–60.
- 15 O'Donnell MD, Candarlioglu CA, Miller CA, Gentleman E, Stevens MM. Materials characterisation and cytotoxic assessment of strontium-substituted bioactive glasses for bone regeneration. J Mater Chem 2010; 20: 8934–8941.
- 16 Saint-Jean SJ, Camiré CL, Nevsten P, Hansen S, Ginebra MP. Study of the reactivity and in vitro bioactivity of Sr-substituted α-TCP cements. J Mater Sci Mater Med 2005; 16: 993–1001.
- 17 Verbeckmoes SC, Best GJ, Oste L, Verbotes AR. Effects of strontium on the physicochemical characteristics of hydroxyapatite. Calcif Tissue Int 2004; 75: 405–415.
- 18 Kim HW, Koh YH, Kong YM, Kang JG, Kim HE. Strontium substituted calcium phosphate biphasic ceramics obtained by a power precipitation method. J Mater Sci Mater Med 2004; 15: 1129–1134.
- 19 Arepalli SK, Tripathi H, Hira SK, Manna PP, Pyare R, Singh SP. Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses. Mater Sci Eng C 2016; 69: 108–116.
- 20 Jones JR. Review of bioactive glass: From Hench to hybrids. Acta Biomater 2013; 9: 4457–4486.
- 21 Lewis G, Xu J, Madigan S, Towler MR, Influence of strontia on various properties of Surgical Simplex® P acrylic bone cement and experimental variants. Acta Biomater 2007; 3: 970–979.
- 22 Li YW, Leong JCY, Lu WW, Luk KDK, Cheung KMC, Chiu PKY, Chow SP. Novel injectable bioactive bone cement for spinal surgery: A development and preclinical study. J Biomed Mat Res 2000; 52: 164–170.
- 23 Hernandez L, Parra J, Vázquez B, López-Bravo A, Collia F, Goñi I, Gurruchaga M, San Román J. Injectable acrylic bone cements for vertebroplasty based on a radiopaque hydroxyapatite. Bioactivity and biocompatibility. J Biomed Mater Res B Appl Biomater 2008; 88B: 103–114.
- 24 Méndez JA, Fernández M, González-Corchón A, Salvado M, Collía F, de Pedro JA, Levenfeld BL, López-Bravo A, Vázquez B, San Román J. Injectable self-curing bioactive acrylic–glass composites charged with specific anti-inflammatory/analgesic agent. Biomaterials 2004; 25: 2381–2392.
- 25 Dagang G, Kewei X, Yong H. The influence of Sr doses on the in vitro biocompatibility and in vivo degradability of single-phase Sr-incorporated HAP cement. J Biomed Mat Res A 2008; 86: 947–958.
- 26 Ni GX, Chiu KY, Lu WW, Wang Y, Zhang YG, Hao LB, Li ZY, Lam WW, Lu SB, Luk KDK, Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty. Biomaterials 2006; 27: 4348–4355
- 27 Stamboulis A, Law RV, Hill R. Characterisation of commercial ionomer glasses using magic angle nuclear magnetic resonance (MASNMR). Biomaterials 2005; 25: 3907–3913.
- 28 Guida A, Towler MR, Wall JG, Hill RG, Eramo S. Preliminary work on the antibacterial effect of strontium in glass ionomer cements. J Mater Sci Lett 2003; 22: 1401–1403.
- 29 Lewis G, Carroll M. Rheological properties of acrylic bone cement during curing and the role of size of the powder particles. J Biomed Mat Res B 2002; 63: 191–199.
- 30 Pascual B, Vázquez B, Gurruchaga M, Goñi I, Ginebra P, Gil J, Planell JA, Levenfeld B, San Román J. New aspects of the effect of size and size distribution on the setting parameters and mechanical properties of acrylic bone cements. Biomaterials 1996; 17: 509–516.
- 31 Hernández L, Gurruchaga M, Goñi I. Influence of powder particle size distribution on complex viscosity and other properties of acrylic bone cement for vertebroplasty and kyphoplasty. J Biomed Mat Res B 2006; 77B: 98–103.
- 32 Zhao F, Lu WW, Luk KDK, Cheung KMC, Wong CT, Leong JCY, Yao KD. Surface treatment of injectable strontium-containing bioactive bone cement for vertebroplasty. J Biomed Mater Res B 2004; 69B: 79–86.
- 33 International Standard ISO 5833. Implants for Surgery-Acrylic Resins Cements. Switzerland: ISO copyright office; 2002.
- 34 Pham QT, Petiaud R, Waton H. Proton and Carbon NMR Spectra of Polymers. Boca Raton (US): CRC Press; 1991.
- 35 Hernandez L, Fernández M, Collia F, Gurruchaga M, Goñi I, Preparation of acrylic bone cements for vertebroplasty with bismuth salicylate as radiopaque agent. Biomaterials 2004; 27: 100–107.
- 36 García Carrodeguas R, Vázquez B, San Román J. Injectable acrylic bone cements for vertebroplasty with improved properties. J Biomed Mater Res B 2004; 68: 94–104
- 37 Dadkhah M, Pontiroli L, Fiorilli S, Manca A, Tallia F, Tcacencu I, Vitale-Brovarone C. Preparation and characterisation of an innovative injectable calcium sulphate based bone cement for vertebroplasty application. J Mater Chem B 2017; 5: 102–115.
- 38 Mossman T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1–2): 55–63.
- 39 Nakayama GR, Caton MC, Nova MP, Parandoosh Z. Assessment of the Alamar Blue assay for cellular growth and viability in vitro. J Immunol Methods 1997; 204: 205–208.
- 40 Kühn KD. Bone Cements. Up-to-date Comparison of Physical and Chemical Properties of Commercial Materials. Berlin: Springer; 2000.
- 41 Lewis G. Viscoelastic properties of injectable bone cements for orthopaedic applications: State of the art review. J Biomed Mater Res B 2011; 998: 171–191.
- 42 Fang J, Shen J, Jiang W, et al. Cytotoxicity of polymethyl methacrylate cement on primary cultured metastatic spinal cells. Mol Cell Toxicol 2016; 12: 125–132.
- 43 Quan C, Tang Y, Liu Z, Rao M, Zhang W, Liang P, Wu N, Zhang C, Shen H, Jiang Q. Effect of modification degree of nanohydroxyapatite on biocompatibility and mechanical property of injectable poly(methylmethacrylate)-based bone cement. J Biomed Mater Res B 2016; 104B: 576–584.
- 44 Sun K, Liu Y, Peng H, Tan J-F, Zhang M, Zhang X-N, Chen F-Z, Li M-H. A comparative study of high-viscosity cement percutaneous vertebroplasty vs. low-viscosity cement percutaneous kyphoplasty for treatment of osteoporotic vertebral compression fractures. J Huazhong Univ Sci Technol [Med Sci] 2016;36: 389–394.
- 45 Lao J, Jallot E, Nedelec JM. Strontium-delivering glasses with enhanced bioactivity: A new biomaterial for antiosteoporotic applications? Chem Mater 2008; 20: 4969–4973.
- 46 Carlsson E, Mestres G, Treerattrakoon K, López A, Karlsson Ott M, Larsson S, Persson C. In vitro and in vivo response to low-modulus PMMA-based bone cement. Biomed Res Int 2015; 2015:art ID 594284, 9.
- 47 Zhang W, Tian Y, He H, Ma Y, Guo H, Yuan Y, Liu C. Strontium attenuates rhBMP-2-induced osteogenic differentiation via formation of Sr-rhBMP-2 complex and suppression of Smad-dependent signalling pathway. Acta Biomater 2016; 33: 290–300.
- 48 Ginebra P, Rilliard A, Fernandez E, Elvira C, San Roman J, Planell JA. J Biomed Mater Res 2001; 5–7: 113–118.
- 49 Debi Ravi N, Balu R, Sampath Kumar TS. Strontium-substituted calcium deficient hydroxyapatite nanoparticles: synthesis, characterization and antibacterial properties. J Am Ceram Soc 2012; 95: 2700–2708.