Restricted accessResearch articleFirst published online 2020-2
Local administration of aspirin improves osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats through activation of the Notch signaling pathway
Osteoporosis-induced impaired bone regeneration would result in compromised osseointegration of hydroxyapatite-coated titanium and high rate of implant failure. Local administration of aspirin promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration in osteoporotic condition. We hypothesized that reduced osteogenesis may account for poor osseointegration of hydroxyapatite-coated titanium which could be ameliorated by using local aspirin. The aim of this study was to confirm the effect of the local incorporation of aspirin into hydroxyapatite-coated titanium implants in the osteoporotic and normal condition. Twelve-week-old female Sprague–Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group Sham, group OVX and group OVX + ASP, and the rats from OVX and Sham received hydroxyapatite-coated implants and animals belong to group OVX + ASP received aspirin-hydroxyapatite-coated implants until death at 12 weeks, respectively. After 12-week healing period, local treatment with aspirin revealed improved osseointegration compared to OVX, with significant improvement of the bone area ratio and bone-to-implant contact in histomorphometry, the bone mass and trabecular architecture in micro-CT evaluation, and the maximal push-out force in push out test. Moreover, group OVX + ASP presented the strongest effect on Jagged1, Notch1, and Hes-1(P < 0.05). These results demonstrated that local administration of aspirin could enhance hydroxyapatite-coated titanium implant osseointegration in OVX rats by activation Wnt signaling pathway to improve implant fixation in osteoporotic bone.
HenrikDBrianETroelsA, et al.
Parathyroid hormone treatment increases fixation of orthopedic implants with gap healing: a biomechanical and histomorphometric canine study of porous coated titanium alloy implants in cancellous bone. Calci Tissue Int2011;
88: 294–303.
2.
CastelliniIAndreaniLParchiPD, et al.
Hydroxyapatite in total hip arthroplasty. Our experience with a plasma spray porous titanium alloy/hydroxyapatite double-coated cementless stem. Clin Cases Miner Bone Metab2016;
13: 221
3.
SuoLJiangNWangY, et al.
The enhancement of osseointegration using a graphene oxide/chitosan/hydroxyapatite composite coating on titanium fabricated by electrophoretic deposition. J Biomed Mater Res Part B Appl Biomater2019; 107: 635–645.
4.
HardyDCFrayssinetPGuilhemA, et al.
Bonding of hydroxyapatite-coated femoral prostheses. Histopathology of specimens from four cases. J Bone Joint Surgery Br Vol1991;
73: 732–740.
5.
HaraTHayashiKNakashimaY, et al.
The effect of hydroxyapatite coating on the bonding of bone to titanium implants in the femora of ovariectomised rats. J Bone Joint Surgery Br Vol1999;
81: 705–709.
6.
RossRDHamiltonJLWilsonBM, et al.
Pharmacologic augmentation of implant fixation in osteopenic bone. Curr Osteoporos Rep2014;
12: 55–64.
7.
CarboneLDTylavskyFACauleyJA, et al.
Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res2010;
18: 1795–1802.
8.
LiuYWangLKikuiriT, et al.
Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nature medicine2011;
17: 1594–1601.
9.
WeiJWangJGongY, et al.
Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats. Molecular Medicine Reports2015;
12: 1717.
10.
TaoZSZhouWSQiangZ, et al.
Intermittent administration of human parathyroid hormone (1–34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur. J Biomater Appl2016;
30: 952–960.
11.
TaoZSZhouWSBaiBL, et al.
The effects of combined human parathyroid hormone (1–34) and simvastatin treatment on the interface of hydroxyapatite-coated titanium rods implanted into osteopenic rats femurs. J Mater Sci Mater Med2016;
27: 43.
12.
YuXWeiM.Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method. J Biomed Mater Res2011;
97B: 345–354.
13.
YuXJiangXRoweD, et al.
Biomimetic CaP coating incorporated with parathyroid hormone improves the osseointegration of titanium implant. J Mater Sci Mater Med2012;
23: 2177–2186.
14.
TaoZSWuXJYangM, et al.
Local administration with silymarin could increase osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats. J Biomater Appl2019;
34: 664–672.
15.
TaoZSWuXJZhouWS, et al.
Local administration of aspirin with beta-tricalcium phosphate/poly-lactic-co-glycolic acid (beta-TCP/PLGA) could enhance osteoporotic bone regeneration. J Bone Miner Metab2019. DOI: 10.1007/s00774-019-01008-w.
16.
VarkeyMKucharskiCDoschakMR, et al.
Osteogenic response of bone marrow stromal cells from normal and ovariectomized rats treated with a low dose of basic fibroblast growth factor. Tissue Eng2007;
13: 809–817.
17.
ZhangYChengNMironR, et al.
Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials2012;
33: 6698–6708.
18.
TaoZSZhouWSTuKK, et al.
The effects of combined human parathyroid hormone (1–34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats. Injury2015;
46: 2164–2169.
19.
LiYFLiXDBaoCY, et al.
Promotion of peri-implant bone healing by systemically administered parathyroid hormone (1–34) and zoledronic acid adsorbed onto the implant surface. Osteoporos Int2013;
24: 1063–1071.
20.
GabetYKohaviDKohlerT, et al.
Trabecular bone gradient in rat long bone metaphyses: mathematical modeling and application to morphometric measurements and correction of implant positioning. J Bone Miner Res2008;
23: 48–57.
21.
LiYLiQZhuS, et al.
The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats. Biomaterials. 2010;
31: 9006–9014.
22.
TaoZSBaiBLHeXW, et al.
A comparative study of strontium-substituted hydroxyapatite coating on implant's osseointegration for osteopenic rats. Med Biol Eng Comput2016;
54: 1959–1968.
23.
TaoZSZhouWSHeXW, et al.
A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C, Mater Biol Appl2016;
62: 226–232.
24.
FabienWClairePLaurentL, et al.
The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation. J Biol Chem2013;
288: 6542–6551.
25.
YangQLiFL.Effect of low dose aspirin on osseointegration around titanium implants in osteoporotic rats. Chin J Stomatol2018;
53: 92–96.
26.
RenLPanSLiH, et al.
Effects of aspirin-loaded graphene oxide coating of a titanium surface on proliferation and osteogenic differentiation of MC3T3-E1 cells. Sci Rep2018;
8: 15143.
27.
LiuHLiWLiuY, et al.
Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin. Stem Cell Res Ther2015;
6: 200.
28.
HanHJKimSHanDH.Multifactorial evaluation of implant failure: a 19-year retrospective study. Int J Oral Maxillofac Implants2014;
29: 303–310.
29.
DavideCLucioMCarla RenataA.The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials2006;
27: 2331–2339.
30.
UezonoMTakakudaKKikuchiM, et al.
Hydroxyapatite/collagen nanocomposite-coated titanium rod for achieving rapid osseointegration onto bone surface †. J Biomed Mater Res. 2013;
101B: 1031–1038.
31.
SirinHTVargelIKutsalT, et al.
Ti implants with nanostructured and HA-coated surfaces for improved osseointegration. Artif Cells2015;
44: 1–8.
32.
WeiJWangJGongY, et al.
Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats. Mol Med Rep2015;
12: 1717.
33.
ChenZWWuZXSangHX, et al.
Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model. Zhonghua yi Xue za Zhi2011;
91: 925–929.
34.
Tao S, J Li, Xing HL, et al. Melatonin improves the osseointegration of hydroxyapatite-coated titanium implants in senile female rats. Z Gerontol Geriatr 2019. DOI: 10.1007/s00391-019-01640-1
35.
Tao ZS, Zhou WS, Wu XJ, et al. Single-dose local administration of parathyroid hormone (1-34, PTH) with β-tricalcium phosphate/collagen (β-TCP/COL) enhances bone defect healing in ovariectomized rats. J Bone Miner Metab 2019; 37: 28--35.
36.
TaoZZhouWJiangY, et al.
Effects of strontium-modified calcium phosphate cement combined with bone morphogenetic protein-2 on osteoporotic bone defects healing in rats. J Biomater Appl2018;
33: 3–10.
37.
ReddiACounterCMWangC, et al.
Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol. 2002;
20: 587.
38.
HuZZhangFYangZ, et al.
Low-dose aspirin promotes endothelial progenitor cell migration and adhesion and prevents senescence. Cell Biol Int2013;
32: 761–768.
39.
TakayoshiYYasuoMYanmingB, et al.
Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One. 2008;
3: 907–911.
40.
CarboneLDTylavskyFACauleyJA, et al.
Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res2003;
18: 1795–1802.
41.
EnginFYaoZYangT, et al.
Dimorphic effects of Notch signaling in bone homeostasis. Nat Med2008;
14: 299–305.
42.
NishantCStephenHAnjaliJ, et al.
Pro-osteogenic topographical cues promote early activation of osteoprogenitor differentiation via enhanced TGFβ, Wnt, and Notch signaling. Clin Oral Implants Res2014;
25: 475–486.
43.
ChinKY.A review on the relationship between aspirin and bone health. J Osteopor2017;
2017: 1–8.
44.
RenLPanSLiH, et al.
Effects of aspirin-loaded graphene oxide coating of a titanium surface on proliferation and osteogenic differentiation of MC3T3-E1 cells. Sci Rep 2018. DOI:10.1038/s41598-018-33353-7.
