Transforming Orthopedic Biomaterials Into Bone Cancer Inhibiting Implants: The Role of Selenium Nanoclusters
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Transforming Orthopedic Biomaterials Into Bone Cancer Inhibiting Implants: The Role of Selenium Nanoclusters Phong A.Tran1, Love Sarin2, Robert H. Hurt2, and Thomas J. Webster3 1 Physics Department, Brown University, Providence, RI 02912, U.S.A. 2 Division of Engineering, Brown University, Providence, RI 02912, U.S.A. 3 Division of Engineering and Department of Orthopedics, Brown University, Providence, RI 02912, U.S.A. ABSTRACT Current orthopedic implants have numerous problems that include poor osseointegration, stress shielding and wear debris-associated bone cell death. In addition, numerous patients receive orthopedic implants as a result of bone cancer resection, yet none of the current orthopedic materials are designed to prevent either the occurrence or reoccurrence of cancer. The objective of this study was to transform a traditional orthopedic material into an implant that can both restore bone and prevent bone cancer growth at the implant-tissue interface. Elemental selenium was chosen as the biologically active agent in this material because of its known chemopreventive and chemotherapeutic properties. It was found that when selenite salts were reduced by glutathione in the presence of an immersed substrate (titanium (Ti), stainless steel (SS) or ultra high molecular weigh polyethylene (UHMWPE)), elemental selenium nucleated and grew into adherent, hemispherical nanoclusters. For each type of substrate (Ti, SS and UHMWPE), three types of surfaces with different selenium surface densities were fabricated. The zero oxidation state of selenium was confirmed on Ti substrates by XPS profiles. Compared to uncoated Ti and SS substrates, the high-density selenium-coated surfaces inhibited cancerous bone cell functions while promoting healthy bone cell functions. Very little selenium was also found to release (about 250ppb) into the cell culture media after 3 days of immersion. These findings showed for the first time the potential of using selenium nanoclusters as a coating to transform a traditional orthopedic material into a bone cancer inhibiting implant. INTRODUCTION It is estimated that 2,380 individuals will be diagnosed with bone and joint cancers and 1,470 individuals will die from primary bone and joint cancers in 2008 in the U.S. [1]. Primary bone cancer is rare as usually bone cancer is a result of the spread of cancer from other organs (such as the lungs, breasts and prostate) [2]. A common technique to treat bone cancer is the surgical removal of the cancerous tissue followed by insertion of an orthopedic implant to restore patient functions. Therefore, it would be beneficial to have implants specifically designed to prevent the occurrence and reoccurrence of bone cancer and promote healthy bone tissue growth. Unfortunately, current materials used as an orthopedic implant do not possess anti-cancer properties and, thus, have no inherent mechanisms to keep cancer from reoccurring. The objective of the present in vitro study was to create an orthopedic implant with anti-cancer chemistry
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