title: N-acetyl cysteine (NAC)-mediated detoxification and functionalization of poly(methyl methacrylate) bone cement.
abstract: Currently used poly(methyl methacrylate) (PMMA)-based bone cement lacks osteoconductivity and induces osteolysis and implant loosening due to its cellular and tissue-toxicity. A high percentage of revision surgery following the use of bone cement has become a significant universal problem. This study determined whether incorporation of the amino acid derivative N-acetyl cysteine (NAC) in bone cement reduces its cytotoxicity and adds osteoconductivity to the material. Biocompatibility and bioactivity of PMMA-based bone cement with or without 25mm NAC incorporation was examined using rat bone marrow-derived osteoblastic cells. Osteoconductive potential of NAC-incorporated bone cement was determined by microCT bone morphometry and implant biomechanical test in the rat model. Generation of free radicals within the polymerizing bone cement was examined using electron spin resonance spectroscopy. Severely compromised viability and completely suppressed phenotypes of osteoblasts on untreated bone cement were restored to the normal level by NAC incorporation. Bone volume formed around 25mm NAC-incorporated bone cement was threefold greater than that around control bone cement. The strength of bone-bone cement integration was 2.2 times greater for NAC-incorporated bone cement. For NAC-incorporated bone cement, the spike of free radical generation ended within 12h, whereas for control bone cement, a peak level lasted for 6 days and a level greater than half the level of the peak was sustained for 20 days. NAC also increased the level of antioxidant glutathione in osteoblasts. These results suggest that incorporation of NAC in PMMA bone cement detoxifies the material by immediate and effective in situ scavenging of free radicals and increasing intracellular antioxidant reserves, and consequently adds osteoconductivity to the material.
authors.affiliation: Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsukimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Aita
authors.forename: Norio
authors.initials: N
authors.lastname: Hori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yoshino
authors.forename: Masaichi
authors.initials: M
authors.lastname: Chang-Il Lee
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kimoto
authors.forename: Anahid
authors.initials: A
authors.lastname: Jewett
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D001843:Bone Cements / Q000737:chemistry* / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D019904:Polymethyl Methacrylate / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials; D001843:Bone Cements; D019904:Polymethyl Methacrylate; D000111:Acetylcysteine