This study investigated the osteogenesis-related cell functions of osteoprogenitor cells modulated by surface chemistry modification using lithium (Li) ions in a current clinical oral implant surface in order to gain insights into the future development of titanium (Ti) implants with enhanced osteogenic capacity. Wet chemical treatment was performed to modify a sandblasted/acid-etched (SLA) Ti implant surface using Li ions. The osteogenesis-related cell response to the surface Li ion-modified SLA sample was evaluated using two kinds of murine bone marrow stem cells, bipotent ST2 cells and primary multipotent mesenchymal stem cells (MSCs). The modified surface exhibited the formation of an Li-containing Ti oxide layer with plate-like nanostructures. The Li-incorporated surface enhanced early cellular events, including spreading, focal adhesion formation and integrin mRNA expression (α2, α5, αv and β3), and accelerated osteogenic differentiation of bipotent ST2 cells compared with unmodified SLA surface. Surface Li modification significantly increased GSK-3β phosphorylation and suppressed β-catenin phosphorylation, and promoted the subsequent osteogenic differentiation of primary MSCs. These results indicate that surface chemistry modification of SLA implants by wet chemical treatment with Li ions induces a more favorable osseointegration outcome through the promotion of the osteogenic differentiation of bone marrow MSCs via the positive regulation of GSK-3β and β-catenin activity.
De BruynHRaesFCooperLF, et al.Three-years clinical outcome of immediate provisionalization of single OsseospeedTM implants in extraction sockets and healed ridges. Clin Oral Implants Res2013; 24: 217–223.
2.
KimHSKimYJJangJH, et al.Surface engineering of nanostructured titanium implants with bioactive ions. J Dent Res2016; 95: 558–565.
3.
GastaldiGGrusovinMGFeliceP, et al.Early loading of maxillary titanium implants with a nanostructured calcium-incorporated surface (Xpeed): 5-year results from a multicentre randomized controlled trial. Eur J Oral Implantol2017; 10: 415–424.
4.
LiZGaoPWanP, et al.Novel bio-functional magnesium coating on porous Ti6Al4V orthopaedic implants: in vitro and in vivo study. Sci Rep2017; 7: 40755.
5.
ChoiSMParkJW. Multifunctional effects of a modification of SLA titanium implant surface with strontium-containing nanostructures on immunoinflammatory and osteogenic cell function. J Biomed Mater Res A2018; 106: 3009–3020.
6.
OffermannsVAndersenOZSillassenM, et al.A comparative in vivo study of strontium-functionalized and SLActiveTM implant surfaces in early bone healing. Int J Nanomedicine2018; 13: 2189–2197.
7.
CooperLFZhouYTakebeJ, et al.Fluoride modification effects on osteoblast behavior and bone formation at TiO2 grit-blasted c.p. titanium endosseous implants. Biomaterials2006; 27: 926–936.
8.
LiLPengZQinY, et al.Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis. Sci Rep2017; 7: 45204.
9.
GuoHWangCWangJ, et al.Lithium-incorporated deproteinized bovine bone substitute improves osteogenesis in critical-sized bone defect repair. J Biomater Appl2018; 32: 1421–1434.
10.
HuangTLiYYuK, et al.Effect of the Wnt signal-RANKL/OPG axis on the enhanced osteogenic integration of a lithium incorporated surface. Biomater Sci2019; 7: 1101–1116.
11.
YuanYYuanQWuC, et al.Enhanced osteoconductivity and osseointegration in calcium polyphosphate bioceramic scaffold via lithium doping for bone regeneration. ACS Biomater Sci Eng2019; 5: 5872–5880.
12.
SatijaNKSharmaDAfrinF, et al.High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage. PLoS One2013; 8: e55769.
13.
ZhuZYinJGuanJ, et al.Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK-3β-dependent β-catenin/Wnt pathway activation. FEBS J2014; 281: 5371–5389.
14.
HouschyarKSTapkingCBorrelliMR, et al.Wnt pathway in bone repair and regeneration - What do we know so far. Front Cell Dev Biol2019; 6: 170.
15.
HolmenSLZylstraCRMukherjeeA, et al.Essential role of β-catenin in postnatal bone acquisition. J Biol Chem2005; 280: 21162–21168.
16.
LiZXuZDuanC, et al.Role of TCF/LEF transcription factors in bone development and osteogenesis. Int J Med Sci2018; 15: 1415–1422.
17.
WongSKChinKYIma-NirwanaS. The skeletal-protecting action and mechanisms of action for mood-stabilizing drug lithium chloride: Current evidence and future potential research areas. Front Pharmacol2020; 11: 430.
18.
PoschATDe Avellar-PintoJFMaltaFS, et al.Lithium chloride improves bone filling around implants placed in estrogen-deficient rats. Arch Oral Biol2020; 111: 104644.
19.
GalliCPiemonteseMLumettiS, et al.GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. Clin Oral Implants Res2013; 24: 921–927.
20.
LiuWChenDJiangG, et al.A lithium-containing nanoporous coating on entangled titanium scaffold can enhance osseointegration through Wnt/β-catenin pathway. Nanomedicine2018; 14: 153–164.
21.
AbrahamssonIBerglundhTLinderE, et al.Early bone formation adjacent to rough and turned endosseous implant surfaces. An experimental study in the dog. Clin Oral Implants Res2004; 14: 381–392.
22.
SalviGEGalliniGLangNP. Early loading (2 or 6 weeks) of sandblasted and acid etched (SLA) ITI® implants in the posterior mandible. A 1-year randomized controlled clinical trial. Clin Oral Implants Res2004; 15: 142–149.
23.
RoccuzzoMAgliettaMBuninoM, et al.Early loading of sandblasted and acid etched implants: a randomized-controlled double blind split-mouth study. Five-year results. Clin Oral Implants Res2008; 19: 148–152.
24.
BuserDJannerSFMWittnebenJG, et al.10-year survival and success rates of 511 titanium implants with a sandblasted and acid-etched surface: a retrospective study in 303 partially edentulous patients. Clin Implant Dent Relat Res2012; 14: 8351–8398.
25.
Olivares-NavarreteRHyzySLParkJH, et al.Mediation of osteogenic differentiation of human mesenchymal stem cells on titanium surfaces by a Wnt-integrin feedback loop. Biomaterials2011; 32: 6399–6411.
26.
LopesHBFreitasGPEliasCN, et al.Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography. J Biomed Mater Res Part A2019; 107: 1303–1313.
27.
HagenTVidal-PuigA. Characterisation of the phosphorylation of β-catenin at the GSK-3 priming site Ser45. Biochem Biophys Res Commun2002; 294: 324–328.
28.
LiuCLiYSemenovM, et al.Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell2002; 108: 837–847.
29.
AmitSHatzubaiABirmanY, et al.Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev2002; 16: 1066–1076.
30.
WuDPanW. GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem Sci2010; 35: 161–168.
31.
GavaganMFagnanESpeltzEB, et al.The scaffold protein Axin promotes signaling specificity within the Wnt pathway by suppressing competing kinase reactions. Cell Syst2020; 10: 515–525.
32.
PerrinDSzmukler-MonclerSEchikouC, et al.Bone response to alteration of surface topography and surface composition of sandblasted and acid-etched (SLA) implants. Clin Oral Implants Res2002; 13: 465–469.
33.
Szmukler-MonclerSBischofMNeirR, et al.Titanium hydride and hydrogen concentration in acid-etched commercially pure titanium and titanium alloy implants: a comparative analysis of five implant systems. Clin Oral Implants Res2010; 21: 944–950.
34.
ChrcanovicBBWennerbergAMartinsMA. Influence of temperature and acid etching time on the superficial characteristics of Ti. Mater Res2015; 18: 963–970.
35.
AronssonBOHjorvarssonBFrauchigerL, et al.Hydrogen desorption from sand-blasted and acid-etched titanium surfaces after glow-discharge treatment. J Biomed Mater Res2001; 54: 20–29.
36.
ParkJWTsutsumiYLeeCS, et al.Surface structure and osteoblast response of hydrothermally produced CaTiO3 thin film on Ti-13Nb-13Zr alloy. Appl Surf Sci2011; 257: 7856–7863.
37.
CherkashininGJaegermannW. Dissociative adsorption of H2O on LiCoO2 (00l) surfaces: Co reduction induced by electron transfer from intrinsic defects. J Chem Phys2016; 144: 184706.
38.
KhangDChoiJImYM, et al.Role of subnano-nano- and submicron-surface features on osteoblast differentiation of bone marrow mesenchymal stem cells. Biomaterials2012; 33: 5997–6007.
39.
FraioliRDashnyamKKimJH, et al.Surface guidance of stem cell behavior: Chemically tailored co-presentation of integrin-binding peptides stimulates osteogenic differentiation in vitro and bone formation in vivo. Acta Biomater2016; 43: 269–281.
40.
ParkJWHanawaTChungJH. The relative effects of Ca and Mg ions on MSC osteogenesis in the surface modification of microrough Ti implants. Int J Nanomedicine2019; 14: 5697–5711.
41.
WangPYThissenHKingshottP. Modulation of human multipotent and pluripotent stem cells using surface nanotopographies and surface-immobilised bioactive signals: a review. Acta Biomater2016; 45: 31–59.
42.
BelloDGFouillenABadiaA, et al.A nanoporous titanium surface promotes the maturation of focal adhesions and formation of filopodia with distinctive nanoscale protrusions by osteogenic cells. Acta Biomater2017; 60: 339–349.
43.
IsoshimaKUenoTAraiY, et al.The change of surface charge by lithium ion coating enhances protein adsorption on titanium. J Mech Behav Biomed Mater2019; 100: 103393.
