N-acetyl cysteine (NAC)-mediated detoxification and functionalization of poly(methyl methacrylate) bone cement

• Published in: Biomaterials Vol. 30; no. 20; pp. 3378 - 3389
• Main Authors: Tsukimura, Naoki, Yamada, Masahiro, Aita, Hideki, Hori, Norio, Yoshino, Fumihiko, Chang-Il Lee, Masaichi, Kimoto, Katsuhiko, Jewett, Anahid, Ogawa, Takahiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2009
• Subjects: Acetylcysteine - chemistry; Acetylcysteine - metabolism; Advanced Basic Science; Animals; Antioxidant; Arthroplasty; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Bone and Bones - cytology; Bone and Bones - metabolism; Bone and Bones - pathology; Bone cement implantation syndrome (BCIS); Bone Cements - chemistry; Bone Cements - metabolism; Bone Regeneration - physiology; Calcification, Physiologic; Cell Proliferation; Cell Survival; Cells, Cultured; Dentistry; Free radical; Humans; Male; Materials Testing; Osteoblasts - cytology; Osteoblasts - metabolism; Phenotype; Polymethyl Methacrylate - chemistry; Polymethyl Methacrylate - metabolism; Rats; Rats, Sprague-Dawley; Total hip replacement; Toxicity; Bone cement implantation syndrome (BCIS); Arthroplasty; Total hip replacement; Antioxidant; Toxicity; Free radical
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.02.043

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 25 m m NAC incorporation was examined using rat bone marrow-derived osteoblastic cells. Osteoconductive potential of NAC-incorporated bone cement was determined by μCT 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 25 m m 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 12 h, 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.