Abstract
The biological properties of nanostructured bioactive ceramic composite (BCC) granules doped with 0.1–10 at.% silver and 0.05–5 at.% copper have been investigated both in vitro and in vivo to develop effective alloplastic material for infected bone defect substitute. It is assumed that the granules consisting of biphasic calcium phosphate and bioactive glass ceramics due to their nanoscale (15–40 nm) and multiphase structure, bioelement placement in different ceramic phases as well as antimicrobial effect should improve osteogenic properties and biocompatibility. Tests in vitro have been conducted with multipotent mesenchymal stromal cells (MSCs) and test strains of microorganisms. The same biocomposite has been used in vivo to study the repair of bone defects in animal model. The findings indicate that doped BCC leads to antimicrobial activity. Inhibition of MSCs growth has been observed for granules doped with ions of more than 1 at.% silver and 0.5 at.% copper. The results of the in vivo study reveal that BCC implantation significantly improves bone reparation. Differences between bone repair with undoped and doped, with 1 at.% silver and 0.5 at.% copper, ceramic samples were not observed. The BCC doped within 0.5–1 at.% silver and 0.25–0.5 at.% copper stimulates bone tissue repair and has satisfactory biocompatibility and antimicrobial properties.
Similar content being viewed by others
References
Balagna C, Vitale-Brovarone C, Miola M, Verné E, Canuto RA, Saracino S, Muzio G, Fucale G, Maina G (2011) Biocompatibility and antibacterial effect of silver doped 3D-glass-ceramic scaffolds for bone grafting. J Biomater Appl 25(6):595–617. doi:10.1177/0885328209356603
Balamurugan A, Balossier G, Laurent-Maquin D, Pina S, Rebelo AH, Faure J, Ferreira JM (2008) An in vitro biological and anti-bacterial study on a sol-gel derived silver-incorporated bioglass system. Dent Mater 24(10):1343–1351. doi:10.1016/j.dental.2008.02.015
Bancroft JD, Stevens A (1990) Theory and practice of histological techniques, 2nd edn. Churchill Livingstone, London
Barralet J, Gbureck U, Habibovic P, Vorndran E, Gerard C, Doillon CJ (2009) Angiogenesis in calcium phosphate scaffolds by inorganic copper ion release. Tissue Eng Part A 15(7):1601–1609. doi:10.1089/ten.tea.2007.0370
Chen W, Oh S, Ong AP, Oh N, Liu Y, Courtney HS, Appleford M, Ong JL (2007) Antibacterial and osteogenic properties hydroxyapatite coatings produced using of silver-containing a sol gel process. J Biomed Mater Res Part A 82A:899–906
Chen J, Wang Y, Chen X et al (2011) A simple sol-gel technique for synthesis of nanostructured hydroxyapatite, tricalcium phosphate and biphasic powders. Mater Lett 65:1923–1926. doi:10.1016/j.matlet.2011.03.076
Daculsi G, Laboux O, Malard O, Weiss P (2003) Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med 14:195–200
Dodwad V, Vaish S, Mahajan A, Chhokra M (2012) Local drug delivery in periodontics: a strategic intervention. Int J Pharm Pharm Sci 4(4):30–34
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8(4):315–317
Dorozhkin SV (2010) Nanosized and nanocrystalline calcium orthophosphates. Acta Biomater 6(3):715–734. doi:10.1016/j.actbio.2009.10.031
Eniwumide JO, Yuan H, Cartmell SH, Meijer GJ, de Bruijn JD (2007) Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded) allograft. Eur Cells Mater 14:30–39
Ewald A, Käppel C, Vorndran E, Moseke C, Gelinsky M, Gbureck U (2012) The effect of Cu(II)-loaded brushite scaffolds on growth and activity of osteoblastic cells. J Biomed Mater Res A 100(9):2392–2400. doi:10.1002/jbm.a.34184
Fan J, Lei J, Yu C, Tu B, Zhao D (2007) Hard-templating synthesis of a novel rod-like nanoporous calcium phosphate bioceramics and their capacity as antibiotic carriers. Mater Chem Phys 103(2–3):489–493
Gerard C, Bordeleau LJ, Barralet J, Doillon CJ (2010) The stimulation of angiogenesis and collagen deposition by copper. Biomaterials 31(5):824–831
Gupta A, Phung LT, Taylor DE, Silver S (2001) Diversity of silver resistance genes in IncH incompatibility group plasmids. Microbiology 147:3393–3402
Hammond JS, Gaarenstroom SW, Winograd N (1975) X-ray photoelectron spectroscopic studies of cadmium- and silver-oxygen surfaces. Anal Chem 47:2193–2199. doi:10.1021/ac60363a019
Heitz-Mayfield L, Tonetti MS, Cortellini P, Lang NP, European Research Group on Periodontology (ERGOPERIO) (2006) Microbial colonization patterns predict the outcomes of surgical treatment of intrabony defects. J Clin Periodontol 33(1):62–68
Hsu YH, Turner IG, Miles AW (2007) Fabrication of porous bioceramics with porosity gradients similar to the bimodal structure of cortical and cancellous bone. J Mater Sci Mater Med 18:2251–2256
International Organization for Standardization (ISO) (2009) Biological evaluation of medical devices, ISO 10993—part 5: tests for in vitro cytotoxicity. International Organization for Standardization, Geneve
Jaiswal S, McHale P, Duffy B (2012) Preparation and rapid analysis of antibacterial silver, copper and zinc doped sol-gel surfaces. Colloids Surf B 94:170–176
Landi E, Logroscino G, Proietti L, Tampieri A, Sandri M, Sprio S (2008) Biomimetic Mg-substituted hydroxyapatite: from synthesis to in vivo behaviour. J Mater Sci Mater Med 19:239–247
Lüthen F, Bergemann C, Bulnheim U et al (2010) A dual role of copper on the surfaces of bone implants. Mater Sci Forum 638–642:600–605
Marambio-Jones C, Hoek EMV (2010) A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment. J Nanopart Res 12:1531–1551. doi:10.1007/s11051-010-9900-y
Munch E, Franco J, Deville S, Hunger P, Saiz E, Tomsia AP (2008) Porous ceramic scaffolds with complex architectures. JOM 60(6):54–58
O’Donnell MD, Fredholm Y, de Rouffignac A, Hill RG (2008) Structural analysis of a series of strontium-substituted apatites. Acta Biomater 4:1455–1464
Parmigiani F, Pacchioni G, Illas F, Bagus PS (1992) Studies of the CuO bond in cupric oxide by X-ray photoelectron spectroscopy and ab initio electronic structure models. J Electron Spectrosc Relat Phenom 59:255–269. doi:10.1016/0368-2048(92)87005-7
Porter AE, Botelho CM, Lopes MA, Santos JD, Best SM, Bonfield W (2004) Ultrastructural comparison of dissolution and apatite precipitation on hydroxyapatite and silicon-substituted hydroxyapatite in vitro and in vivo. J Biomed Mater Res 69A(4):670–679
Rameshbabu N, Sampath Kumar TS, Prabhakar TG, Sastry VS, Murty KV, Prasad Rao K (2007) Antibacterial nanosized silver substituted hydroxyapatite: synthesis and characterization. J Biomed Mater Res A. 80(3):581–591
Rodriguez JP, Rios S, Gonzalez M (2002) Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper. J Cell Biochem 85(1):92–100
Sanchez-Salcedo S, Izquierdo-Barba I, Arcos D, Vallet-Regio M (2006) In vitro evaluation of potential calcium phosphate scaffolds for tissue engineering. Tissue Eng 12:279–290
Schön G, Tummavuori J, Lindström B et al (1973) ESCA Studies of Ag, Ag2O and AgO. Acta Chem Scand 27:2623–2633. doi:10.3891/acta.chem.scand.27-2623
Shanmugam S, Gopal B (2014) Copper substituted hydroxyapatite and fluorapatite: synthesis, characterization and antimicrobial properties. Ceram Int 40(10):15655–15662. doi:10.1016/j.ceramint.2014.07.086
Shepherd JH, Shepherd DV, Best SM (2012) Substituted hydroxyapatites for bone repair. J Mater Sci Mater Med 23(10):2335–2347. doi:10.1007/s10856-012-4598-2
Sogo Y, Ito A, Fukasawa K, Sakurai T, Ichinose N (2004) Zinc containing hydroxyapatite ceramics to promote osteoblastic cell activity. Mater Sci Technol 20(9):1079–1084. doi:10.1179/026708304225019704
Spence G, Patel N, Brooks R, Rushton N (2009) Carbonate substituted hydroxyapatite: resorption by osteoclasts modifies the osteoblastic response. J Biomed Mater Res 90A(1):217–224
Stoscheck CM (1990) Quantitation of protein. Methods Enzymol 182:50–69
Thanyaphoo S, Kaewsrichan J (2012) Synthesis and evaluation of novel glass ceramics as drug delivery systems in osteomyelitis. J Pharm Sci 101(8):2870–2882. doi:10.1002/jps.23230
Wu C, Zhou Y, Xu M, Han P, Chen L, Chang J, Xiao Y (2013) Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity. Biomaterials 34(2):422–433. doi:10.1016/j.biomaterials.2012.09.066
Xing ZC, Chae WP, Baek JY, Choi MJ, Jung Y, Kang IK (2010) In vitro assessment of antibacterial activity and cytocompatibility of silver-containing PHBV nanofibrous scaffolds for tissue engineering. Biomacromolecules 11(5):1248–1253. doi:10.1021/bm1000372
Acknowledgments
The authors gratefully acknowledge the support of Dr. Olena Voloshuk from Bogomolets National Medical University (Ukraine), the Department of Microbiology, Virology, and Immunology. Dmytro Zubov, leading researcher and Roman Vasyliev, researcher from State Institute of Genetic and Regenerative Medicine of NAMS (Ukraine), in the implementation phases of the study. We express profound gratitude to Prof. Anatolii Levitskyi for the access to biochemical laboratory and vivarium facilities at State Institute of Stomatology of NAMS (Odesa, Ukraine). This project is financially supported by Branch target preparation Kyiv National Taras Shevchenko University, NAMS of Ukraine (Grant No. 0114U003876).
Conflict of interest
The authors have no financial interest in any of the companies or products, devices, and biomedical preparation mentioned in this manuscript. Therefore, authors have no conflict of interests.
Author information
Authors and Affiliations
Corresponding author
Additional information
Guest Editor: Liudmyla Rieznichenko
This article is part of the topical collection on Engineered Bioinspired Nanomaterials
Rights and permissions
About this article
Cite this article
Lysenko, O., Dubok, O., Borysenko, A. et al. The biological properties of the silver- and copper-doped ceramic biomaterial. J Nanopart Res 17, 178 (2015). https://doi.org/10.1007/s11051-015-2971-z
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-015-2971-z