期刊
出版社
ELSEVIER
DOI: 10.1016/j.msec.2021.111878
关键词
Simvastatin; Immune response; Antibacterial; Osteogenesis; Nanotubes
资金
- National Natural Science Foundation of China [51901239, 52001076]
- Natural Science Foundation of Hebei Province of China [E2020202028, E2017202032]
- China Postdoctoral Science Foundation [2019M662830]
- Science and Technology Commission of Shanghai Municipality [18YF1426900]
This study introduced simvastatin-loaded TiO2 nanotubes layered with a thermosensitive hydrogel, which showed enhanced differentiation in osteoblasts and in vivo antibacterial activity in subcutaneous infection. The combination material holds promise for orthopedic implant applications.
Although Ti is widely used in orthopedic implants, its bio-inert characteristics and poor antibacterial activity may result in implant failure. To counter this problem, in this study, we loaded simvastatin, a bioactive compound that promotes osteogenesis, in TiO2 nanotubes and a thermosensitive chitosan-glycerin-hydroxypropyl methyl cellulose hydrogel (CGHH) was then layered on top of these nanotubes. At normal human-body temperature (37 degrees C), CGHH was present in a sol state, thus facilitating the controlled release of simvastatin to enhance differentiation in MC3T3-E1 osteoblasts. In vitro cell-culture studies suggested that CGHH in a gel state would induce macrophage polarization to the pro-inflammatory M1 phenotype. In vitro testing against Escherichia coli and Staphylococcus aureus indicated no antibacterial activity in CGHH in both sol and gel states. However, the results of subcutaneous infection animal models suggested that CGHH showed excellent in vivo antibacterial activity, which can be explained by the fact at high temperatures induced by an infection, CGHH transitioned into a gel state and released large amounts of glycerin. Such a high glycerin dosage induced an acute inflammatory reaction and antibacterial activity. Thus, due to their enhanced osteogenesis capacity at normal body temperature and antibacterial characteristics in the presence of infection, the newly designed simvastatin-loaded CGHH-encapsulated TiO2 nanotubes are promising materials for application in orthopedic implants.
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