ARTICLE IN PRESS Biomaterials xxx(2009)1-12 Contents lists available at science Direct Biomaterial Biomaterials ELSEVIER journalhomepagewww.elsevier.com/locate/biomaterials In vitro and in vivo evaluation of an alumina-zirconia composite for arthroplasty applications Olivier roualdes a,, Marie-Eve Duclos. 1. Dan Gutknecht b, 2, Lucien Frappart Jerome Chevalier b, 2. Daniel]. Hartmann a Universite de Lyon, UPSP 2007.03.135, Reparation Tissulaire, Interactions Biologiques et Biomateriaux, Universite Claude Bemard Lyon 1.8 Rockefeller-69373 b Universite de Lyon, INSA de Lyon, UMR CNRS 5510, 20 avenue Albert Einstein 69621 Villeurbanne Cedex, France Universite de lyon, INSERM U590, Pharmacogenomique et Chimioresistance, Laboratoire d'Anatomopathologie, Hopital Edouard Herriot, Bat. B, 5 place d'Arsonval-69437 LYON cedex 03. franc ARTICLE INFO A BSTRACT Article history. n order to improve the reliability and the mechanical properties of orthor Received 23 October 2009 ceramic composites starting with nanosized powders of alumina and zir ave been recently vailable online xxx developed. The aim of the present study was to investigate the biological tolerance of one of these sintered ceramics and of its alumina and zirconia constitutive nanosized powders with both in vitro and in vivo approaches. At first, osteoblasts and fibroblasts were cultured either upon sintered ceramic discs with polished or rough surfaces or in the presence of the corresponding alumina or zirconia powders at In vitro, the materials showed no deleterious effect on cell proliferation, extra-cellular matrix produ(.ts. various concentrations. Thereafter, we chronically injected these powders in the knee articulation of ra (human type I collagen and fibronectin) or on cell morphology In vivo, the histological examination showed only a very moderate and non-specific granulomatous response of the synovial membrane but o major inflammation as clinically described with metals or polyethylene wear debris. Besides its mproved physical properties, this recently developed alumina-zirconia composite showed satisfactory biocompatibility e 2009 Elsevier Ltd. All rights reserved. 1. Introduction arthroplasty were introduced more than 20 years ago [7-9]. Their use reduces wear rates of bearing components and produces Due to the increase of the life expectancy, the number of total negligible amount of ion release by comparison with metals ol hip arthroplasties is steadily growing. The lifetime of hip implants polymers. The clinical success associated to the use of ceramic has generally ranges from 12 to 15 years. In recent years, we have led to the implantation of more than 3.5 millions alumina observed a significant increase in revision surgery, which are components and more than 600,000 zirconia femoral heads frequently associated with clinical complications. It is therefore worldwide since 1990 [10]. If these materials show many advan- crucial to improve lifetime, reliability and biocompatibility of tages compared to metal, they have also shown some limitations. thopaedic implants such as hip prosthesis There is indeed a higher risk of fracture associated with ceramic Various combinations of different designs and materials have components [11, 12], even if it is strongly reduced today for both been proposed for acetabular cups and femoral heads 1-6. alumina and zirconia [12, 13. Some clinical studies show also Ceramic materials such as zirconia and alumina for total hip a hydrothermal degradation(often referred as aging) of zirconia [14 whose phase transformation is accelerated in aqueous ng author..Te:+33478777518;fax:+33478772819 ronment [15]. E-mail addresses: olivier roualdes@gmailcom(O. Roualdes). me. duclos@vet-lyon. The clinical success of a new ceramic material lies firstly on its ncgevanergr f f D Gutlinec ifrappartechu-lyon fr ability to resist to crack propagation and failure. New generations of che. univ-lyon1 fr(DJ. Hartmann). recently developed alumina-zirconia composites, often starting lel:+33478777518;fax:+33478772819 with very fine nanosized powders, meet this purpose [10, 16, 17]. 33472436125;fax:+33472438528 Such composites have also been demonstrated as safe against aging 3Tel:+33478785673;fax:+33478772819. 18. However, before a human clinical use, biological inocuity must .9612/s- see front matter o 2009 Elsevier Ltd. All rights reserved 0. 1016/ biomaterials. 2009.11. Please cite this article in press as: Roualdes 0, et al, In vitro and in vivo evaluation of an, Biomaterials(2009). doi: 10.1016/ j biomaterials 2009. 11.107In vitro and in vivo evaluation of an alumina–zirconia composite for arthroplasty applications Olivier Roualdes a,*, Marie-Eve Duclos a,1 , Dan Gutknecht b,2 , Lucien Frappart c , Je´ roˆme Chevalier b,2 , Daniel J. Hartmann a,3 aUniversite´ de Lyon, UPSP 2007.03.135, Re´paration Tissulaire, Interactions Biologiques et Biomate´riaux, Universite´ Claude Bernard Lyon 1, 8 avenue Rockefeller – 69373 Lyon Cedex 08, France bUniversite´ de Lyon, INSA de Lyon, UMR CNRS 5510, 20 avenue Albert Einstein 69621 Villeurbanne Cedex, France cUniversite´ de Lyon, INSERM U590, Pharmacoge´nomique et Chimiore´sistance, Laboratoire d’Anatomopathologie, Hoˆpital Edouard Herriot, Bat. B, 5 place d’Arsonval – 69437 LYON cedex 03, France article info Article history: Received 23 October 2009 Accepted 26 November 2009 Available online xxx Keywords: Ceramic Composite Alumina Zirconia Nanoparticles Biocompatibility abstract In order to improve the reliability and the mechanical properties of orthopaedic hip prosthesis, new ceramic composites starting with nanosized powders of alumina and zirconia have been recently developed. The aim of the present study was to investigate the biological tolerance of one of these sintered ceramics and of its alumina and zirconia constitutive nanosized powders with both in vitro and in vivo approaches. At first, osteoblasts and fibroblasts were cultured either upon sintered ceramic discs with polished or rough surfaces or in the presence of the corresponding alumina or zirconia powders at various concentrations. Thereafter, we chronically injected these powders in the knee articulation of rats. In vitro, the materials showed no deleterious effect on cell proliferation, extra-cellular matrix production (human type I collagen and fibronectin) or on cell morphology. In vivo, the histological examination showed only a very moderate and non-specific granulomatous response of the synovial membrane but no major inflammation as clinically described with metals or polyethylene wear debris. Besides its improved physical properties, this recently developed alumina–zirconia composite showed satisfactory biocompatibility. 2009 Elsevier Ltd. All rights reserved. 1. Introduction Due to the increase of the life expectancy, the number of total hip arthroplasties is steadily growing. The lifetime of hip implants generally ranges from 12 to 15 years. In recent years, we have observed a significant increase in revision surgery, which are frequently associated with clinical complications. It is therefore crucial to improve lifetime, reliability and biocompatibility of orthopaedic implants such as hip prosthesis. Various combinations of different designs and materials have been proposed for acetabular cups and femoral heads [1–6]. Ceramic materials such as zirconia and alumina for total hip arthroplasty were introduced more than 20 years ago [7–9]. Their use reduces wear rates of bearing components and produces negligible amount of ion release by comparison with metals or polymers. The clinical success associated to the use of ceramic has led to the implantation of more than 3.5 millions alumina components and more than 600,000 zirconia femoral heads worldwide since 1990 [10]. If these materials show many advan￾tages compared to metal, they have also shown some limitations. There is indeed a higher risk of fracture associated with ceramic components [11,12], even if it is strongly reduced today for both alumina and zirconia [12,13]. Some clinical studies show also a hydrothermal degradation (often referred as aging) of zirconia [14] whose phase transformation is accelerated in aqueous envi￾ronment [15]. The clinical success of a new ceramic material lies firstly on its ability to resist to crack propagation and failure. New generations of recently developed alumina–zirconia composites, often starting with very fine nanosized powders, meet this purpose [10,16,17]. Such composites have also been demonstrated as safe against aging [18]. However, before a human clinical use, biological inocuity must * Corresponding author. Tel.: þ33 4 78 77 75 18; fax: þ33 4 78 77 28 19. E-mail addresses: olivier.roualdes@gmail.com (O. Roualdes), me.duclos@vet-lyon. fr (M.-E. Duclos), dan.gutknecht@insa-lyon.fr (D. Gutknecht), l.frappart@chu-lyon.fr (L. Frappart), jerome.chevalier@insa-lyon.fr (J. Chevalier), daniel.hartmann@recher￾che.univ-lyon1.fr (D.J. Hartmann). 1 Tel.: þ33 4 78 77 75 18; fax: þ33 4 78 77 28 19. 2 Tel.: þ33 4 72 43 61 25; fax: þ33 4 72 43 85 28. 3 Tel.: þ33 4 78 78 56 73; fax: þ33 4 78 77 28 19. Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials ARTICLE IN PRESS 0142-9612/$ – see front matter 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2009.11.107 Biomaterials xxx (2009) 1–12 Please cite this article in press as: Roualdes O, et al., In vitro and in vivo evaluation of an..., Biomaterials (2009), doi:10.1016/ j.biomaterials.2009.11.107