Titanium (Ti) and Ti alloys are widely used biomaterials, but they lack osteogenic capability for rapid bone integration. To improve osseointegration of Ti implants, TiO2 nanotubes were prepared using the anodizing oxidation technique, and strontium (Sr) combined with icariin (ICA) was loaded on TiO2 nanotube coatings. Cell adhesion and proliferation of MC3T3-E1 cells, alkaline phosphatase (ALP) activity, mineralization of extracellular matrix, and bone formation around titanium implants in ovariectomized rats, were examined separately. The results showed that compared with pure Ti, TiO2 and Sr-loaded TiO2 coatings, the coatings loaded with both Sr and ICA showed better effect on cell adhesion and proliferation, higher ALP activity and more red-stained mineralized nodules. Furthermore, more bone was formed around implants loaded with both Sr and ICA in osteoporotic rats. Therefore, coating with Sr and ICA is valuable for clinical application to strengthen the osseointegration of titanium implants, especially in osteoporotic patients.
MiaoXWangDXuL, et al.
The response of human osteoblasts, epithelial cells, fibroblasts, macrophages and oral bacteria to nanostructured titanium surfaces: a systematic study. Ijn2017;
12: 1415–1430.
2.
AlbrektssonTDahlinCReinedahlD, et al.
An imbalance of the immune system instead of a disease behind marginal bone loss around oral implants: position paper. Int J Oral Maxillofac Implants2020;
35: 495–502.
3.
TrindadeRAlbrektssonTGalliS, et al.
Osseointegration and foreign body reaction: titanium implants activate the immune system and suppress bone resorption during the first 4 weeks after implantation. Clin Implant Dent Relat Res2018;
20: 82–91.
4.
LiXMaXFengY, et al.
Osseointegration of chitosan coated porous titanium alloy implant by reactive oxygen species-mediated activation of the PI3K/AKT pathway under diabetic conditions. Biomaterials2015;
36: 44–54.
5.
MengHWChienEYChienHH.Dental implant bioactive surface modifications and their effects on osseointegration: a review. Biomark Res2016;
4: 24.
6.
KimMParkKChoiK, et al.
Cell adhesion and in vivo osseointegration of sandblasted/acid etched/anodized dental implants. Int J Mol Sci2015;
16: 10324–10336.
7.
OkuzuYFujibayashiSYamaguchiS, et al.
In vitro study of antibacterial and osteogenic activity of titanium metal releasing strontium and silver ions. J Biomater Appl2021;
35: 670–680.
8.
BrammerKSFrandsenCJJinS.TiO2 nanotubes for bone regeneration. Trends Biotechnol2012;
30: 315–322.
9.
MillerPD.Management of severe osteoporosis. Expert Opin Pharmacother2016;
17: 473–488.
10.
QuadeMVaterCSchlootzS, et al.
Strontium enhances BMP-2 mediated bone regeneration in a femoral murine bone defect model. J Biomed Mater Res B Appl Biomater2020;
108: 174–182.
11.
OffermannsVAndersenOZRiedeG, et al.
Effect of strontium surface-functionalized implants on early and late osseointegration: a histological, spectrometric and tomographic evaluation. Acta Biomater2018;
69: 385–394.
12.
AleneziAGalliSAtefyektaS, et al.
Osseointegration effects of local release of strontium ranelate from implant surfaces in rats. J Mater Sci Mater Med2019;
30: 116.
13.
ZhangXLiuTHuangY, et al.
Icariin: does it have an osteoinductive potential for bone tissue engineering?Phytother Res2014;
28: 498–509.
14.
ZhaoJOhbaSKomiyamaY, et al.
Icariin: a potential osteoinductive compound for bone tissue engineering. Tissue Eng Part A2010;
16: 233–243.
15.
ZhaoJOhbaSShinkaiM, et al.
Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner. Biochem Biophys Res Commun2008;
369: 444–448.
16.
SongYMaANingJ, et al.
Loading icariin on titanium surfaces by phase-transited lysozyme priming and layer-by-layer self-assembly of hyaluronic acid/chitosan to improve surface osteogenesis ability. Int J Nanomedicine2018;
13: 6751–6767.
17.
ZhangY-YZhuYLuD-Z, et al.
Evaluation of osteogenic and antibacterial properties of strontium/silver-containing porous TiO2 coatings prepared by micro-arc oxidation. J Biomed Mater Res B Appl Biomater. Epub ahead of print 31 August 2020. DOI: 10.1002/jbm.b.34719.
18.
LiangYQQiMCXuJ, et al.
Low-magnitude high-frequency loading, by whole-body vibration, accelerates early implant osseointegration in ovariectomized rats. Mol Med Rep2014;
10: 2835–2842.
19.
LiQWangXLuX, et al.
The incorporation of daunorubicin in cancer cells through the use of titanium dioxide whiskers. Biomaterials2009;
30: 4708–4715.
20.
CochranDLSchenkRKLussiA, et al.
Bone response to unloaded and loaded titanium implants with a sandblasted and acid-etched surface: a histometric study in the canine mandible. J Biomed Mater Res1998;
40: 1–11.
21.
LarssonLDeckerAMNibaliL, et al.
Regenerative medicine for periodontal and peri-implant diseases. J Dent Res2016;
95: 255–266.
22.
HuYCaiKLuoZ, et al.
TiO2 nanotubes as drug nanoreservoirs for the regulation of mobility and differentiation of mesenchymal stem cells. Acta Biomater2012;
8: 439–448.
23.
ZhaoLWangHHuoK, et al.
The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates. Biomaterials2013;
34: 19–29.
24.
WuTNanKChenJ, et al.
A new bone repair scaffold combined with chitosan/hydroxyapatite and sustained releasing icariin. Chin Sci Bull2009;
54: 2953–2961.
25.
KargozarSLotfibakhshaieshNAiJ, et al.
Strontium- and cobalt-substituted bioactive glasses seeded with human umbilical cord perivascular cells to promote bone regeneration via enhanced osteogenic and angiogenic activities. Acta Biomater2017;
58: 502–514.
26.
PilmaneMSalma-AncaneKLocaD, et al.
Strontium and strontium ranelate: historical review of some of their functions. Mater Sci Eng C Mater Biol Appl2017;
78: 1222–1230.
27.
LiangYLiHXuJ, et al.
Morphology, composition, and bioactivity of strontium-doped brushite coatings deposited on titanium implants via electrochemical deposition. Int J Mol Sci2014;
15: 9952–9962.
28.
JingZYanCYingW, et al.
A comparative study on the metabolism of epimedium koreanum nakai-prenylated flavonoids in rats by an intestinal enzyme (lactase phlorizin hydrolase) and intestinal flora. Molecules2013;
19: 177–203.
29.
LiuYHuangLHaoB, et al.
Use of an osteoblast overload damage model to probe the effect of icariin on the proliferation, differentiation and mineralization of MC3T3-E1 cells through the wnt/β-Catenin signalling pathway. Cell Physiol Biochem2017;
41: 1605–1615.
30.
WangZWangDYangD, et al.
The effect of icariin on bone metabolism and its potential clinical application. Osteoporos Int2018;
29: 535–544.
31.
ZhangYXiangQDongS, et al.
Fabrication and characterization of a recombinant fibronectin/cadherin bio-inspired ceramic surface and its influence on adhesion and ossification in vitro. Acta Biomater2010;
6: 776–785.
32.
ZengJGuoJSunZ, et al.
Osteoblastic and anti-osteoclastic activities of strontium-substituted silicocarnotite ceramics: in vitro and in vivo studies. Bioact Mater2020;
5: 435–446.
33.
KazemiMDehghanMMAzamiM.Biological evaluation of porous nanocomposite scaffolds based on strontium substituted β-TCP and bioactive glass: an in vitro and in vivo study. Mater Sci Eng C Mater Biol Appl2019;
105: 110071.
34.
ZhouLPoonCC-WWongK-Y, et al.
Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling. Phytomedicine2020;
19: 153413.
35.
XieLLiuNXiaoY, et al.
In vitro and in vivo osteogenesis induced by icariin and bone morphogenetic protein-2: a dynamic observation. Front Pharmacol2020;
11: 1058.
36.
MarxDRahimnejad YazdiAPapiniM, et al.
A review of the latest insights into the mechanism of action of strontium in bone. Bone Rep2020;
12: 100273.
37.
GoltzmanDHendyGN.The calcium-sensing receptor in bone-mechanistic and therapeutic insights. Nat Rev Endocrinol2015;
11: 298–307.
38.
MariePJ.The calcium-sensing receptor in bone cells: a potential therapeutic target in osteoporosis. Bone2010;
46: 571–576.
