title: Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta).
abstract: Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many alloys induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (duration, 0 to 14 y) were evaluated for changes in their hematology, coagulation, and serum chemistry profiles. Negative controls (n = 28) did not have implants. Macaques with implants had higher plasma D-dimer and lower antithrombin III concentrations than nonimplanted animals. In addition, animals with implants had higher globulin and lower albumin and calcium concentrations compared with nonimplanted macaques. Many of these changes were positively correlated with duration of implantation and the number of implants. Chronic bacterial infection of the skin was present around many of the implant sites and within deeper tissues. Representative histopathology around the implant site of 2 macaques revealed chronic suppurative to pyogranulomatous inflammation extending from the skin to the dura mater. X-ray fluorescence microscopy of tissue biopsies from the implant site of the same 2 animals revealed significantly higher levels of free metal ions in the tissue, including titanium and iron. The higher levels of free metal ions persisted in the tissues for as long as 6 mo after explantation. These results suggest that long-term skull-anchored percutaneous titanium alloy implants can be associated with localized inflammation, chronic infection, and leaching of metal ions into local tissues.
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Division of Surgery, Science, and Bioengineering, Advanced Tissue Resource Center, Massachusetts General Hospital, Boston, Massachusetts;, Email: gfrydman@mit.edu.
authors.forename: Galit H
authors.initials: GH
authors.lastname: Frydman
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Marini
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Bakthavatchalu
authors.affiliation: Drug Safety Research and Development, Pfizer, Groton, Connecticut.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Biddle
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Muthupalani
authors.affiliation: Advanced Tissue Resource Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Vanderburg
authors.affiliation: X-ray Science Division, Argonne National Laboratory, US Department of Energy, Argonne, Illinois.
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.affiliation: Harvard Medical School, Division of Hematology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Pavan K
authors.initials: PK
authors.lastname: Bendapudi
authors.affiliation: Division of Surgery, Science, and Bioengineering, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000497:Alloys; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001672:Biocompatible Materials; D002908:Chronic Disease; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D007501:Iron / Q000032:analysis; D008253:Macaca mulatta; D008297:Male; D019736:Prostheses and Implants / Q000009:adverse effects*; D012886:Skull / Q000601:surgery; D013997:Time Factors; D014025:Titanium / Q000009:adverse effects* / Q000032:analysis / Q000097:blood
chemical_list: D000497:Alloys; D001672:Biocompatible Materials; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D000990:Antithrombin III; D014025:Titanium; D007501:Iron