Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis
Oxidative stress induced by the overproduction of reactive oxygen species (ROS) during the interaction between titanium (Ti) surfaces and cells commonly results in delayed or compromised osteogenic differentiation. To counteract intracellular ROS overproduction and the oxidized microenvironment, we...
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Elsevier
2025-01-01
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| Series: | Journal of Materials Research and Technology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2238785424029892 |
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| author | Huichuan Xu Kosuke Nozaki Ziniu Yu Nobuyuki Kawashima Takeshi Ueno Huaze Wu Hao Wu Noriyuki Wakabayashi |
| author_facet | Huichuan Xu Kosuke Nozaki Ziniu Yu Nobuyuki Kawashima Takeshi Ueno Huaze Wu Hao Wu Noriyuki Wakabayashi |
| author_sort | Huichuan Xu |
| collection | DOAJ |
| description | Oxidative stress induced by the overproduction of reactive oxygen species (ROS) during the interaction between titanium (Ti) surfaces and cells commonly results in delayed or compromised osteogenic differentiation. To counteract intracellular ROS overproduction and the oxidized microenvironment, we constructed vinylphosphonic acid-glutathione (VPA-GSH) conjugates synthesized through a thiol-ene click reaction on Ti substrates, endowing them with good biocompatibility, antioxidant capability, and promotion of osteogenesis. In addition, a substantial amount of GSH was controllably released after transferring the VPA-GSH-loaded Ti substrate from a synthetic solution at pH 3.6 to phosphate-buffered saline at pH 7.4. The release began with 1 h and gradually increased, reaching its peak concentration of 39.6 μM between 96 and 120 h. X-ray photoelectron spectroscopy revealed differences in the chemical composition, accompanied by concurrent sulfur and phosphorus peaks, indicating the synthesis and covalent binding of the VPA-GSH conjugates onto the Ti surfaces. Treating Ti surfaces with improved hydrophilicity containing diverse functional groups effectively enhanced MC3T3-E1 cell attachment. The well-developed cytoskeleton and increased vinculin expression in MC3T3-E1 cells showed the biocompatibility of the VPA-GSH-binding Ti surfaces. Moreover, VPA-GSH-treated Ti surfaces facilitated alkaline phosphatase activity and extracellular matrix (ECM) mineralization. Runt-related transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) gene expression level were significantly up-regulated on VPA-GSH-treated Ti surfaces. Furthermore, low ROS fluorescence intensity in individual cells indicated their regulatory effects. The oxidative stress microenvironment simulated using hydrogen peroxide (H2O2) showed that Ti substrates immobilizing VPA-GSH conjugates efficiently scavenged H2O2 and rescued cell viability owing to the controlled release of GSH. Altogether, the proposed strategy demonstrates the potential application of novel antioxidant Ti biomaterials to promote osteogenesis against oxidative stress. |
| format | Article |
| id | doaj-art-f506c1ff125d437abe0db71ef5135548 |
| institution | Kabale University |
| issn | 2238-7854 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Materials Research and Technology |
| spelling | doaj-art-f506c1ff125d437abe0db71ef51355482025-01-19T06:25:45ZengElsevierJournal of Materials Research and Technology2238-78542025-01-013428722884Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesisHuichuan Xu0Kosuke Nozaki1Ziniu Yu2Nobuyuki Kawashima3Takeshi Ueno4Huaze Wu5Hao Wu6Noriyuki Wakabayashi7Department of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, Japan; Corresponding author. Department of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanDepartment of Advanced Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, JapanOxidative stress induced by the overproduction of reactive oxygen species (ROS) during the interaction between titanium (Ti) surfaces and cells commonly results in delayed or compromised osteogenic differentiation. To counteract intracellular ROS overproduction and the oxidized microenvironment, we constructed vinylphosphonic acid-glutathione (VPA-GSH) conjugates synthesized through a thiol-ene click reaction on Ti substrates, endowing them with good biocompatibility, antioxidant capability, and promotion of osteogenesis. In addition, a substantial amount of GSH was controllably released after transferring the VPA-GSH-loaded Ti substrate from a synthetic solution at pH 3.6 to phosphate-buffered saline at pH 7.4. The release began with 1 h and gradually increased, reaching its peak concentration of 39.6 μM between 96 and 120 h. X-ray photoelectron spectroscopy revealed differences in the chemical composition, accompanied by concurrent sulfur and phosphorus peaks, indicating the synthesis and covalent binding of the VPA-GSH conjugates onto the Ti surfaces. Treating Ti surfaces with improved hydrophilicity containing diverse functional groups effectively enhanced MC3T3-E1 cell attachment. The well-developed cytoskeleton and increased vinculin expression in MC3T3-E1 cells showed the biocompatibility of the VPA-GSH-binding Ti surfaces. Moreover, VPA-GSH-treated Ti surfaces facilitated alkaline phosphatase activity and extracellular matrix (ECM) mineralization. Runt-related transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) gene expression level were significantly up-regulated on VPA-GSH-treated Ti surfaces. Furthermore, low ROS fluorescence intensity in individual cells indicated their regulatory effects. The oxidative stress microenvironment simulated using hydrogen peroxide (H2O2) showed that Ti substrates immobilizing VPA-GSH conjugates efficiently scavenged H2O2 and rescued cell viability owing to the controlled release of GSH. Altogether, the proposed strategy demonstrates the potential application of novel antioxidant Ti biomaterials to promote osteogenesis against oxidative stress.http://www.sciencedirect.com/science/article/pii/S2238785424029892Dental implantsSurface characterizationsThiol-ene click reactionGlutathioneAntioxidantOsteogenesis |
| spellingShingle | Huichuan Xu Kosuke Nozaki Ziniu Yu Nobuyuki Kawashima Takeshi Ueno Huaze Wu Hao Wu Noriyuki Wakabayashi Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis Journal of Materials Research and Technology Dental implants Surface characterizations Thiol-ene click reaction Glutathione Antioxidant Osteogenesis |
| title | Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis |
| title_full | Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis |
| title_fullStr | Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis |
| title_full_unstemmed | Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis |
| title_short | Surface functionalization of titanium implants with controlled-release glutathione conjugate for antioxidant and osteogenesis |
| title_sort | surface functionalization of titanium implants with controlled release glutathione conjugate for antioxidant and osteogenesis |
| topic | Dental implants Surface characterizations Thiol-ene click reaction Glutathione Antioxidant Osteogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2238785424029892 |
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