To design titanium (Ti)-based biomaterials with controlled drug-releasing bioactive property, TiO2 nanotubes with a diameter of approximately 110 nm was fabricated by electrochemical anodization. TiO2 nanotubes were then loaded with naringin by direct dropping and coated with chitosan layers. The surface morphologies, chemical compositions and wettability of different substrates were characterized by field emission scanning electron microscopy, atomic force microscope, X-ray photoelectron spectroscopy and contact angle measurement, respectively. The in vitro release behavior of naringin was evaluated by UV-visible-spectrophotometer. The biological properties of osteoblasts on different substrates were investigated in vitro. Our results indicate that the chitosan-coated naringin-loaded TiO2 nanotubes enhanced osteoblast spreading, proliferation, alkaline phosphatase activity and late-stage osteoblast mineralization. This study provides a platform to help enhance osteointegration between the bone and implant surface in clinical applications.
LongMRackHJ.Titanium alloys in total joint replacement-a materials science perspective. Biomaterials1998;
19: 1621–1639.
2.
BanSIwayaYKonoHet al.
Surface modification of titanium by etching in concentrated sulfuric acid. Dent Mater2006;
22: 1115–1120.
3.
NishiguchiSNakamuraTKobayashiMet al.
The effect of heat treatment on bone-bonding ability of alkali-treated titanium. Biomaterials1999;
20: 491–500.
4.
RadinSDucheyneP.Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material. Biomaterials2007;
28: 1721–1729.
5.
GongDGrimesCAVargheseOKet al.
Titanium oxide nanotube arrays prepared by anodic oxidation. J Mater Res2011;
16: 3331–3334.
6.
CaiKYRechtenbachAHaoJYet al.
Polysaccharide-protein surface modification of titanium via a layer-by-layer technique: characterization and cell behaviour aspects. Biomaterials2005;
26: 5960–5971.
7.
ManiGJohnsonDMMartonDet al.
Drug delivery from gold and titanium surfaces using self-assembled monolayers. Biomaterials2008;
29: 4561–4573.
8.
OhSDaraioCChenLHet al.
Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes. J Biomed Mater Res A2006;
78: 97–103.
9.
BauerSParkJVondMKet al.
Improved attachment of mesenchymal stem cells on super-hydrophobic TiO2 nanotubes. Acta Biomater2008;
4: 1576–1582.
10.
PopatKCEltgrothMLatempaTJet al.
Titania nanotubes: a novel platform for drug-eluting coatings for medical implants. Small2010;
3: 1878–1881.
11.
LaiMJinZYYangXYet al.
The controlled release of simvastatin from TiO2 nanotubes to promote osteoblast differentiation and inhibit osteoclast resorption. Appl Surf Sci2017;
396: 1741–1751.
12.
BalasundaramGYaoCWebsterTJ.TiO2 nanotubes functionalized with regions of bone morphogenetic protein-2 increases osteoblast adhesion. J Biomed Mater Res A2008;
84: 447–453.
13.
GaoAHangRHuangXet al.
The effects of titania nanotubes with embedded silver oxide nanoparticles on bacteria and osteoblasts. Biomaterials2014;
35: 4223–4235.
14.
SwiaderKLamer-ZarawskaE.Flavonoids of rare Artemisia species and their antifungal properties. Fitoterapia1996;
67: 77–78.
15.
WangXLWangNLZhangYet al.
Effects of eleven flavonoids from the osteoprotective fraction of Drynaria fortunei (KUNZE) J. SM. on osteoblastic proliferation using an osteoblast-like cell line. Chem Pharm Bull2008;
56: 46–51.
16.
JeongJCLeeJWYoonCHet al.
Stimulative effects of Drynariae Rhizoma extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. J Ethnopharmacol2005;
96: 489–495.
17.
WuJBFongYCTsaiHYet al.
Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts. Eur J Pharmacol2008;
588: 333–341.
18.
WongRWKRabieABMHäggEUO.The effect of crude extract from Radix Dipsaci on bone in mice. Phytother Res2007;
21: 596–598.
19.
YuMFYouDQZhuangJJet al.
Controlled release of naringin in metal-organic framework-loaded mineralized collagen coating to simultaneously enhance osseointegration and antibacterial activity. ACS Appl Mater Interfaces2017;
9: 19698–19705.
20.
JiYWangLWattsDCet al.
Controlled-release naringin nanoscaffold for osteoporotic bone healing. Dent Mater2014;
30: 1263–1273.
21.
WongRWRabieAB.Effect of naringin collagen graft on bone formation. Biomaterials2006;
27: 1824–1831.
22.
LiCHWangJWHoMHet al.
Immobilization of naringin onto chitosan substrates by using ozone activation. Colloids Surf B Biointerfaces2014;
747: 1–7.
23.
WangDMaWWangFet al.
Stimulation of Wnt/β-Catenin signaling to improve bone development by naringin via interacting with AMPK and Akt. Cell Physiol Biochem2015;
36: 1563–1576.
24.
ChenLLLeiLHDingPHet al.
Osteogenic effect of Drynariae Rhizoma extracts and naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Arch Oral Biol2011;
56: 1655–1662.
25.
DiMASittingerMRisbudMV.Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials2005;
26: 5983–5990.
26.
CroisierFJérômeC.Chitosan-based biomaterials for tissue engineering. Euro Polym J2013;
49: 780–792.
27.
LaiMCaiKYZhaoLet al.
Surface functionalization of TiO2 nanotubes with bone morphogenetic protein 2 and its synergistic effect on the differentiation of mesenchymal stem cells. Biomacromolecules2011;
12: 1097–1105.
28.
HuYCaiKYLuoZet al.
TiO2 nanotubes as drug nanoreservoirs for the regulation of mobility and differentiation of mesenchymal stem cells. Acta Biomater2012;
8: 439–448.
29.
CaiKYYaoKDCuiLYet al.
Influence of different surface modification treatments on poly(d, l-lactic acid) with silk fibroin and their effects on the culture of osteoblast in vitro. Biomaterials2001;
23: 1603–1611.
30.
YangWHXiXFYangSet al.
Surface engineering of titanium alloy substrates with multilayered biomimetic hierarchical films to regulate the growth behaviors of osteoblasts. Acta Biomater2014;
10: 4525–4536.
31.
WebsterTJErgunCDoremusRHet al.
Enhanced functions of osteoblasts on nanophase ceramics. Biomaterials2000;
21: 1803–1810.
32.
ShenXKHuYXuGQet al.
Regulation of the biological functions of osteoblasts and bone formation by Zn-incorporated coating on microrough titanium. ACS Appl Mater Interfaces2014;
6: 16426–16440.
33.
AnselmeK.Osteoblast adhesion on biomaterials. Biomaterials2000;
21: 667–681.
FakhryASchneiderGBZahariasRet al.
Chitosan supports the initial attachment and spreading of osteoblasts preferentially over fibroblasts. Biomaterials2004;
25: 2075–2079.
36.
ParkJBauerSSchlegelKAet al.
TiO2 nanotube surfaces: 15 nm-an optimal length scale of surface topography for cell adhesion and differentiationSmall2009;
5: 666–671.
37.
LeeJYNamSHImSYet al.
Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. J Control Release2002;
78: 187–197.
38.
WlodarskiKHReddiAH.Alkaline phosphatase as a marker of osteoinductive cells. Calcif Tissue Int1986;
39: 382–385.
39.
ParkYJKimKHLeeJYet al.
Immobilization of bone morphogenetic protein-2 on a nanofibrous chitosan membrane for enhanced guided bone regeneration. Biotechnol Appl Biochem2006;
43: 17–24.
40.
YonezawaTLeeJWHibinoAet al.
Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling. Biochem Biophys Res Commun2011;
409: 260–265.
41.
GaharwarAKSchexnailderPJJinQet al.
Addition of chitosan to silicate cross-linked PEO for tuning osteoblast cell adhesion and mineralization. ACS Appl Mater Interfaces2010;
2: 3119–3127.
KhorELimLY.Implantable applications of chitin and chitosan. Biomaterials2003;
24: 2339–2349.
44.
LiXMaXYFengYFet 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.
45.
ChuaPHNeohKGKangETet al.
Surface functionalization of titanium with hyaluronic acid/chitosan polyelectrolyte multilayers and RGD for promoting osteoblast functions and inhibiting bacterial adhesion. Biomaterials2008;
29: 1412–1421.
SurampalliGK NanjwadeBPatilPA.Corroboration of naringin effects on the intestinal absorption and pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ rat models. Drug Dev Ind Pharm2015;
41: 1057–1065.
48.
FanJLiJFanQ.Naringin promotes differentiation of bone marrow stem cells into osteoblasts by upregulating the expression levels of microRNA-20a and downregulating the expression levels of PPARγ. Mol Med Rep2015;
12: 4759–4765.
49.
ZhangPDaiKRYanSGet al.
Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. Eur J Pharmacol2009;
607: 1–5.
