title: Biocompatibility of fixation materials in the brain.
abstract: Recent clinical reports documenting passive intracranial translocation of microplates and microscrews have prompted concerns regarding brain biocompatibility and neurotoxicity of fixation hardware used in craniofacial surgery. Although the effects of commercially pure titanium. Vitallium (cobalt-chromium-molybdenum), stainless steel, and various alloys have been well assessed in bone and soft tissues, there are no comprehensive studies of these materials in the brain. To investigate this, the biocompatibility of titanium, vitallium, and 316L stainless steel was evaluated in the rabbit brain and compared with silicone elastomer shunt tubing, a material that is used commonly as a neurosurgical implant material with well-established brain biocompatibility. Forty-eight juvenile New Zealand White rabbits were randomly assigned to one of three groups and underwent placement of either commercially pure titanium microscrews, vitallium microscrews, or 316L monofilament stainless steel wire into the parietal region. Silicone elastomer strips of similar size were implanted in the contralateral hemisphere of each rabbit. Animals were assessed daily for signs of neurotoxicity. Rabbits in each group were sacrificed at 2, 4, 8, and 26 weeks following implantation. Brains were sectioned at the implantation site and were examined by means of standard hematoxylin and eosin stains and with immunohistochemical markers sensitive to inflammatory changes in the brain. None of the animals showed any behavioral changes or neurologic deficits suggestive of either systemic or localized toxicity from the implant materials. Silicone clastomer was found to cause the least amount of inflammation relative to other materials tested at all sacrifice points, suggesting that as a standard neurosurgical implant material, it is an appropriate control for studies of brain biocompatibility. At 2 weeks, titanium was found to cause the largest inflammatory response in surrounding brain parenchyma based on analysis of markers for microglial proliferation, gliosis, and leukocyte infiltration. At the 26-week endpoint of our study, the biocompatibility of titanium was nearly equal to the biocompatibility of vitallium based on all studied markers of inflammation. A progressive increase in the inflammatory response surrounding stainless steel implants was noted at 8 and 26 weeks. Relative to all materials studied, at 26 weeks the greatest leukocyte response was found with stainless steel implants. Our results indicate that at the 26-week end-point of our study, titanium and vitallium incited a similar inflammatory response in the rabbit brain that was greater than the response found with silicone elastomer, a standard neurosurgical implant material, but less than that found with stainless steel wire, which is commonly recommended as an alternative fixation material.
authors.affiliation: Department of Plastic, Reconstructive, and Maxillofacial Surgery, Johns Hopkins University School of Medicine, Baltimore 21287-0981, Md, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Mofid
authors.forename: R C
authors.initials: RC
authors.lastname: Thompson
authors.forename: C A
authors.initials: CA
authors.lastname: Pardo
authors.forename: P N
authors.initials: PN
authors.lastname: Manson
authors.forename: C A
authors.initials: CA
authors.lastname: Vander Kolk
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001672:Biocompatible Materials / Q000633:toxicity*; D001863:Bone Screws / Q000009:adverse effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008422:Materials Testing / Q000379:methods; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D012826:Silicone Elastomers / Q000009:adverse effects; D013193:Stainless Steel / Q000633:toxicity*; D013997:Time Factors; D014025:Titanium / Q000633:toxicity*; D014800:Vitallium / Q000633:toxicity*
chemical_list: D001672:Biocompatible Materials; D012826:Silicone Elastomers; D013193:Stainless Steel; D014800:Vitallium; D014025:Titanium