Wu Tao, Tan Lei, Cheng Ning, Yan Qi, Zhang Yu-Feng, Liu Chuan-Jun, Shi Bin
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China.
Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, PR China.
Mater Sci Eng C Mater Biol Appl. 2016 May;62:888-96. doi: 10.1016/j.msec.2016.01.012. Epub 2016 Jan 8.
This work presented a sustained release system of simvastatin (SIM) based on the mesoporous hydroxyapatite (MHA) capped with poly(N-isopropylacrylamide) (PNIPAAM). The MHA was prepared by using cetyltrimethylammonium bromide (CTAB) as a template and the modified PNIPAAM layer on the surface of MHA was fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). The SIM loaded MHA-PNIPAAM showed a sustained release of SIM at 37 °C over 16 days. The bone marrow mesenchymal stem cell (BMSC) proliferation was assessed by cell counting kit-8 (CCK-8) assay, and the osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining. The release profile showed that the release of SIM from MHA-SIM-PNIPAAM lasted 16 days and the cumulative amount of released SIM was almost seven-fold than MHA-SIM. Besides, SIM loaded MHA-PNIPAAM exhibited better performance on cell proliferation, ALP activity, and calcium deposition than pure MHA due to the sustained release of SIM. The quantity of ALP in MHA-SIM-PNIPAAM group was more than two fold than pure MHA group at 7 days. Compared to pure MHA, better BMSC attachment on PNIPAAM modified MHA was observed using fluorescent microscopy, indicating the better biocompatibility of MHA-PNIPAAM.
这项工作展示了一种基于聚(N-异丙基丙烯酰胺)(PNIPAAM)包覆的介孔羟基磷灰石(MHA)的辛伐他汀(SIM)缓释系统。通过使用十六烷基三甲基溴化铵(CTAB)作为模板制备MHA,并通过表面引发的原子转移自由基聚合(SI-ATRP)在MHA表面制备改性的PNIPAAM层。负载SIM的MHA-PNIPAAM在37℃下显示SIM持续释放超过16天。通过细胞计数试剂盒-8(CCK-8)测定评估骨髓间充质干细胞(BMSC)的增殖,并通过碱性磷酸酶(ALP)活性和茜素红染色评估成骨分化。释放曲线表明,SIM从MHA-SIM-PNIPAAM的释放持续16天,释放的SIM累积量几乎是MHA-SIM的七倍。此外,由于SIM的持续释放,负载SIM的MHA-PNIPAAM在细胞增殖、ALP活性和钙沉积方面比纯MHA表现出更好的性能。在第7天,MHA-SIM-PNIPAAM组中的ALP量比纯MHA组多两倍以上。与纯MHA相比,使用荧光显微镜观察到PNIPAAM改性的MHA上有更好的BMSC附着,表明MHA-PNIPAAM具有更好的生物相容性。