Novel Osteogenic Behaviors around Hydrophilic and Radical-Free 4-META/MMA-TBB: Implications of an Osseointegrating Bone Cementopen access
- Authors
- Sugita, Yoshihiko; Okubo, Takahisa; Saita, Makiko; Ishijima, Manabu; Torii, Yasuyoshi; Tanaka, Miyuki; Iwasaki, Chika; Sekiya, Takeo; Tabuchi, Masako; Rezaei, Naser Mohammadzadeh; Taniyama, Takashi; Sato, Nobuaki; Saruta, Juri; Hasegawa, Masakazu; Hirota, Makoto; Park, Wonhee; Lee, Masaichi Chang-Il; Maeda, Hatsuhiko; Ogawa, Takahiro
- Issue Date
- Apr-2020
- Publisher
- MDPI
- Keywords
- arthroplasty; total hip replacement; free radical; PMMA; cytotoxicity; implants
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.7, pp.1 - 24
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 21
- Number
- 7
- Start Page
- 1
- End Page
- 24
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/145954
- DOI
- 10.3390/ijms21072405
- ISSN
- 1661-6596
- Abstract
- Poly(methyl methacrylate) (PMMA)-based bone cement, which is widely used to affix orthopedic metallic implants, is considered bio-tolerant but lacks osteoconductivity and is cytotoxic. Implant loosening and toxic complications are significant and recognized problems. Here we devised two strategies to improve PMMA-based bone cement: (1) adding 4-methacryloyloxylethyl trimellitate anhydride (4-META) to MMA monomer to render it hydrophilic; and (2) using tri-n-butyl borane (TBB) as a polymerization initiator instead of benzoyl peroxide (BPO) to reduce free radical production. Rat bone marrow-derived osteoblasts were cultured on PMMA-BPO, common bone cement ingredients, and 4-META/MMA-TBB, newly formulated ingredients. After 24 h of incubation, more cells survived on 4-META/MMA-TBB than on PMMA-BPO. The mineralized area was 20-times greater on 4-META/MMA-TBB than PMMA-BPO at the later culture stage and was accompanied by upregulated osteogenic gene expression. The strength of bone-to-cement integration in rat femurs was 4- and 7-times greater for 4-META/MMA-TBB than PMMA-BPO during early- and late-stage healing, respectively. MicroCT and histomorphometric analyses revealed contact osteogenesis exclusively around 4-META/MMA-TBB, with minimal soft tissue interposition. Hydrophilicity of 4-META/MMA-TBB was sustained for 24 h, particularly under wet conditions, whereas PMMA-BPO was hydrophobic immediately after mixing and was unaffected by time or condition. Electron spin resonance (ESR) spectroscopy revealed that the free radical production for 4-META/MMA-TBB was 1/10 to 1/20 that of PMMA-BPO within 24 h, and the substantial difference persisted for at least 10 days. The compromised ability of PMMA-BPO in recruiting cells was substantially alleviated by adding free radical-scavenging amino-acid N-acetyl cysteine (NAC) into the material, whereas adding NAC did not affect the ability of 4-META/MMA-TBB. These results suggest that 4-META/MMA-TBB shows significantly reduced cytotoxicity compared to PMMA-BPO and induces osteoconductivity due to uniquely created hydrophilic and radical-free interface. Further pre-clinical and clinical validations are warranted.
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