J R Soc Interface. 2006 December 22; 3(11): 767–775.

Published online 2006 August 15. doi: 10.1098/rsif.2006.0145.

PMCID: PMC1885365

Copyright © 2006 The Royal Society

Biological tolerance of different materials in bulk and nanoparticulate form in a rat model: sarcoma development by nanoparticles

Torsten Hansen,^1* Gaëlle Clermont,² Antonio Alves,² Rosy Eloy,² Christoph Brochhausen,¹ Jean Pierre Boutrand,² Antonietta M Gatti,³ and C James Kirkpatrick¹

¹Institute of Pathology, Johannes Gutenberg-University of Mainz, Langenbeckstr. 1, 55101 Mainz, Germany

²Biomatech S.A., Zone Industrielle de I'Islon, 115 Rue Pasteur, 38670 Chasse-sur-Rhône, France

³Laboratorio dei Biomateriali, Universita degli studi di Modena e Reggio Emilia, Via Campi 231a, 41100 Modena, Italy

^*Author for correspondence (Email: hansen@pathologie.klinik.uni-mainz.de)

Received June 13, 2006; Accepted July 7, 2006.

Abstract

In order to study the pathobiological impact of the nanometre-scale of materials, we evaluated the effects of five different materials as nanoparticulate biomaterials in comparison with bulk samples in contact with living tissues. Five groups out of 10 rats were implanted bilaterally for up to 12 months with materials of the same type, namely TiO₂, SiO₂, Ni, Co and polyvinyl chloride (PVC), subcutaneously with bulk material on one side of the vertebral column and intramuscularly with nanoparticulate material on the contralateral side. At the end of each implantation time, the site was macroscopically examined, followed by histological processing according to standard techniques. Malignant mesenchymal tumours (pleomorphic sarcomas) were obtained in five out of six cases of implanted Co nanoparticle sites, while a preneoplastic lesion was observed in an animal implanted with Co in bulk form. In the Ni group, all animals rapidly developed visible nodules at the implanted sites between 4 and 6 months, which were diagnosed as rhabdomyosarcomas. Since the ratio of surface area to volume did not show significant differences between the Ni/Co group and the TiO₂/SiO₂/PVC group, we suggested that the induction of neoplasia was not mediated by physical effects, but was mediated by the well-known carcinogenic impact of Ni and Co. The data from the Co group show that the physical properties (particulate versus bulk form) could have a significant influence on the acceleration of the neoplastic process.