Titanium is commonly and successfully used in dental and orthopedic implants. However, patients still have to face the risk of implant failure due to various reasons, such as implant loosening or infection. The risk of implant loosening can be countered by optimizing the osteointegration capacity of implant materials. Implant surface modifications for structuring, roughening and biological activation in favor for osteogenic differentiation have been vastly studied. A key factor for a successful stable long-term integration is the initial cellular response to the implant material. Hence, cell-material interactions, which are dependent on the surface parameters, need to be considered in the implant design. Therefore, this review starts with an introduction to the basics of cell-material interactions as well as common surface modification techniques. Afterwards, recent research on the impact of osteogenic processes in vitro and vivo provoked by various surface modifications is reviewed and discussed, in order to give an update on currently applied and developing implant modification techniques for enhancing osteointegration.

Clinic and Polyclinic for Trauma Surgery University Regensburg Medical Centre Regensburg Germany

Experimental Trauma Surgery Department of Trauma Surgery University Regensburg Medical Centre Regensburg Germany

New Technologies Research Centre University of West Bohemia Pilsen Czech Republic

See more in PubMed

Shah FA, Trobos M, Thomsen P, Palmquist A. Commercially pure titanium (cp‐Ti) versus titanium alloy (Ti6Al4V) materials as bone anchored implants—is one truly better than the other? Mater Sci Eng. 2016;62:960‐966. PubMed

Ottria L, Lauritano D, Andreasi Bassi M, et al. Mechanical, chemical and biological aspects of titanium and titanium alloys in implant dentistry. J Biol Regul Homeost Agents. 2018;32(2, suppl 1):81‐90. PubMed

Huynh V, Ngo NK, Golden TD. Surface activation and pretreatments for biocompatible metals and alloys used in biomedical applications. Int J Biomater. 2019;2019:3806504. 10.1155/2019/3806504 PubMed DOI PMC

Pirraco RP, Marques AP, Reis RL. Cell interactions in bone tissue engineering. J Cell Mol Med. 2010;14(1–2):93‐102. 10.1111/j.1582-4934.2009.01005.x PubMed DOI PMC

Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J. 2001;10(suppl 2):96‐101. PubMed PMC

Kieswetter K, Schwartz Z, Dean DD, Boyan BD. The role of implant surface characteristics in the healing of bone. Crit Rev Oral Biol Med. 1996;7(4):329‐345. 10.1177/10454411960070040301 PubMed DOI

Annunziata M, Guida L. The effect of titanium surface modifications on dental implant osseointegration. Front Oral Biol. 2015;17:62‐77. 10.1159/000381694 PubMed DOI

Wennerberg A, Albrektsson T. Effects of titanium surface topography on bone integration: a systematic review. Clin Oral Implants Res. 2009;20(suppl 4):172‐184. 10.1111/j.1600-0501.2009.01775.x PubMed DOI

Smeets R, Stadlinger B, Schwarz F, et al. Impact of dental implant surface modifications on osseointegration. Biomed Res Int. 2016;2016:6285620. 10.1155/2016/6285620 PubMed DOI PMC

Li J, Cui X, Hooper GJ, Lim KS, Woodfield TBF. Rational design, bio‐functionalization and biological performance of hybrid additive manufactured titanium implants for orthopaedic applications: a review. J Mech Behav Biomed Mater. 2020;105:103671. 10.1016/j.jmbbm.2020.103671 PubMed DOI

de Jonge LT, Leeuwenburgh SCG, Wolke JGC, Jansen JA. Organic–inorganic surface modifications for titanium implant surfaces. Pharm Res. 2008;25(10):2357‐2369. 10.1007/s11095-008-9617-0 PubMed DOI

Ramazanoglu M, Oshi Y. Osseointegration and bioscience of implant surfaces—current concepts at bone‐implant Interface. In: Turkyilmaz I, ed. Implant Dentistry—A Rapidly Evolving Practice. London, United Kingdom: IntechOpen Limited; 2011. 10.5772/16936. DOI

Jones JR. Observing cell response to biomaterials. Mater Today. 2006;9(12):34‐43. 10.1016/S1369-7021(06)71741-2 DOI

Beauvais S, Drevelle O, Jann J, et al. Interactions between bone cells and biomaterials: an update. Front Biosci (Schol Ed). 2016;8:227‐263. 10.2741/s460 PubMed DOI

Shah FA, Thomsen P, Palmquist A. Osseointegration and current interpretations of the bone‐implant interface. Acta Biomater. 2019;84:1‐15. 10.1016/j.actbio.2018.11.018 PubMed DOI

Kim Y, Meade SM, Chen K, et al. Nano‐architectural approaches for improved intracortical interface technologies. Front Neurosci. 2018;12:456. 10.3389/fnins.2018.00456 PubMed DOI PMC

Hynes RO. Integrins. Cell. 2002;110(6):673‐687. 10.1016/S0092-8674(02)00971-6 PubMed DOI

Murphy CM, O'Brien FJ, Little DG, Schindeler A. Cell‐scaffold interactions in the bone tissue engineering triad. Eur Cell Mater. 2013;26:120‐132. 10.22203/ecm.v026a09 PubMed DOI

Faia‐Torres AB, Goren T, Ihalainen TO, et al. Regulation of human mesenchymal stem cell osteogenesis by specific surface density of fibronectin: a gradient study. ACS Appl Mater Interfaces. 2015;7(4):2367‐2375. 10.1021/am506951c PubMed DOI

Ode A, Duda GN, Glaeser JD, et al. Toward biomimetic materials in bone regeneration: functional behavior of mesenchymal stem cells on a broad spectrum of extracellular matrix components. J Biomed Mater Res A. 2010;95(4):1114‐1124. 10.1002/jbm.a.32909 PubMed DOI

Schwab EH, Halbig M, Glenske K, Wagner A‐S, Wenisch S, Cavalcanti‐Adam EA. Distinct effects of RGD‐glycoproteins on integrin‐mediated adhesion and osteogenic differentiation of human mesenchymal stem cells. Int J Med Sci. 2013;10(13):1846‐1859. 10.7150/ijms.6908 PubMed DOI PMC

Khullar D, Duggal N, Kaur S. Nanotechnology: an upcoming frontier in implant dentistry. Saint Int Dent J. 2015;1(2):86. 10.4103/2454-3160.177929 DOI

Balshe A, Assad DA, Eckert SE, Koka S, Weaver AL. A retrospective study of the survival of smoothand rough‐surface dental implants. Int J Oral Maxillofac Implants. 2009;24(6):1113‐1118. PubMed

Paszek MJ, Boettiger D, Weaver VM, Hammer DA. Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput Biol. 2009;5(12):e1000604. 10.1371/journal.pcbi.1000604 PubMed DOI PMC

Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in mechanotransduction. J Biol Chem. 2004;279(13):12001‐12004. 10.1074/jbc.R300038200 PubMed DOI

Olivares‐Navarrete R, Raz P, Zhao G, et al. Integrin alpha2beta1 plays a critical role in osteoblast response to micron‐scale surface structure and surface energy of titanium substrates. Proc Natl Acad Sci U S A. 2008;105(41):15767‐15772. 10.1073/pnas.0805420105 PubMed DOI PMC

Souza JCM, Sordi MB, Kanazawa M, et al. Nano‐scale modification of titanium implant surfaces to enhance osseointegration. Acta Biomater. 2019;94:112‐131. 10.1016/j.actbio.2019.05.045 PubMed DOI

Hanawa T. Titanium‐tissue interface reaction and its control with surface treatment. Front Bioeng Biotechnol. 2019;7:170. 10.3389/fbioe.2019.00170 PubMed DOI PMC

Shalabi MM, Gortemaker A, Van't Hof MA, et al. Implant surface roughness and bone healing: a systematic review. J Dent Res. 2006;85(6):496‐500. 10.1177/154405910608500603 PubMed DOI

Matteson JL, Greenspan DC, Tighe TB, Gilfoy N, Stapleton JJ. Assessing the hierarchical structure of titanium implant surfaces. J Biomed Mater Res B Appl Biomater. 2016;104(6):1083‐1090. 10.1002/jbm.b.33462 PubMed DOI

Anil S, Anand PS, Alghamdi H, Jansen JA. Dental Implant Surface Enhancement and Osseointegration. Turkyilmaz I, Implant Dentistry ‐ A Rapidly Evolving Practice; London, United Kingdom: IntechOpen Limited; 2011. 10.5772/16475. DOI

Hanawa T. A comprehensive review of techniques for biofunctionalization of titanium. J Periodontal Implant Sci. 2011;41(6):263‐272. 10.5051/jpis.2011.41.6.263 PubMed DOI PMC

Liu W, Liu S, Wang L. Surface modification of biomedical titanium alloy: micromorphology, microstructure evolution and biomedical applications. Coatings. 2019;9(4):249. 10.3390/coatings9040249 DOI

Qiu Z‐Y, Chen C, Wang X‐M, Lee I‐S. Advances in the surface modification techniques of bone‐related implants for last 10 years. Regen Biomater. 2014;1(1):67‐79. 10.1093/rb/rbu007 PubMed DOI PMC

Subramani K. Titanium surface modification techniques for implant fabrication—from microscale to the nanoscale. JBBTE. 2010;5:39‐56. 10.4028/www.scientific.net/JBBTE.5.39 DOI

Chen X, Fan H, Deng X, et al. Scaffold structural microenvironmental cues to guide tissue regeneration in bone tissue applications. Nanomaterials (Basel). 2018;8(11):960. 10.3390/nano8110960 PubMed DOI PMC

Feller L, Jadwat Y, Khammissa RAG, Meyerov R, Schechter I, Lemmer J. Cellular responses evoked by different surface characteristics of intraosseous titanium implants. Biomed Res Int. 2015;2015:171945. 10.1155/2015/171945 PubMed DOI PMC

Dohan Ehrenfest DM, Coelho PG, Kang B‐S, Sul Y‐T, Albrektsson T. Classification of osseointegrated implant surfaces: materials, chemistry and topography. Trends Biotechnol. 2010;28(4):198‐206. 10.1016/j.tibtech.2009.12.003 PubMed DOI

Rosa MB, Albrektsson T, Francischone CE, Schwartz Filho HO, Wennerberg A. The influence of surface treatment on the implant roughness pattern. J Appl Oral Sci. 2012;20(5):550‐555. 10.1590/s1678-77572012000500010 PubMed DOI PMC

Albrektsson TWA. Oral implant surfaces: part 1—review focusing on topographic and chemical properties of different surfaces and in vivo responses to them. Int J Prosthodont. 2004;17(5):536‐543. PubMed

Calciolari E, Hamlet S, Ivanovski S, Donos N. Pro‐osteogenic properties of hydrophilic and hydrophobic titanium surfaces: crosstalk between signalling pathways in in vivo models. J Periodontal Res. 2018;53(4):598‐609. 10.1111/jre.12550 PubMed DOI

Rausch‐fan X, Qu Z, Wieland M, Matejka M, Schedle A. Differentiation and cytokine synthesis of human alveolar osteoblasts compared to osteoblast‐like cells (MG63) in response to titanium surfaces. Dent Mater. 2008;24(1):102‐110. 10.1016/j.dental.2007.03.001 PubMed DOI

Wang W, Caetano G, Ambler WS, et al. Enhancing the hydrophilicity and cell attachment of 3D printed PCL/graphene scaffolds for bone tissue engineering. Materials (Basel). 2016;9(12):992. 10.3390/ma9120992 PubMed DOI PMC

Deng Y, Liu X, Xu A, et al. Effect of surface roughness on osteogenesis in vitro and osseointegration in vivo of carbon fiber‐reinforced polyetheretherketone‐nanohydroxyapatite composite. Int J Nanomed. 2015;10:1425‐1447. 10.2147/IJN.S75557 PubMed DOI PMC

Wennerberg A, Hallgren C, Johansson C, Danelli S. A histomorphometric evaluation of screw‐shaped implants each prepared with two surface roughnesses. Clin Oral Implants Res. 1998;9(1):11‐19. 10.1034/j.1600-0501.1998.090102.x PubMed DOI

Lin X, Zhou L, Li S, Lu H, Ding X. Behavior of acid etching on titanium: topography, hydrophility and hydrogen concentration. Biomed Mater. 2014;9(1):15002. 10.1088/1748-6041/9/1/015002 PubMed DOI

Szmukler‐Moncler S, Bischof M, Nedir R, Ermrich M. 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 Res. 2010;21(9):944‐950. 10.1111/j.1600-0501.2010.01938.x PubMed DOI

Mariscal‐Muñoz E, Costa CAS, Tavares HS, et al. Osteoblast differentiation is enhanced by a nano‐to‐micro hybrid titanium surface created by Yb:YAG laser irradiation. Clin Oral Investig. 2016;20(3):503‐511. 10.1007/s00784-015-1533-1 PubMed DOI

Maino BG, Di Blasio A, Spadoni D, et al. The integration of orthodontic miniscrews under mechanical loading: a pre‐clinical study in rabbit. Eur J Orthod. 2017;39(5):519‐527. 10.1093/ejo/cjw069 PubMed DOI

Trisi P, Berardini M, Colagiovanni M, Berardi D, Perfetti G. Laser‐treated titanium implants: an in vivo histomorphometric and biomechanical analysis. Implant Dent. 2016;25(5):575‐580. 10.1097/ID.0000000000000457 PubMed DOI

Guarnieri R, Grande M, Ippoliti S, Iorio‐Siciliano V, Riccitiello F, Farronato D. Influence of a laser‐lok surface on immediate functional loading of implants in single‐tooth replacement: three‐year results of a prospective randomized clinical study on soft tissue response and esthetics. Int J Periodontics Restorative Dent. 2015;35(6):865‐875. 10.11607/prd.2273 PubMed DOI

Shah FA, Ruscsák K, Palmquist A. 50 years of scanning electron microscopy of bone‐a comprehensive overview of the important discoveries made and insights gained into bone material properties in health, disease, and taphonomy. Bone Res. 2019;7:15. 10.1038/s41413-019-0053-z PubMed DOI PMC

Tiainen L, Abreu P, Buciumeanu M, et al. Novel laser surface texturing for improved primary stability of titanium implants. J Mech Behav Biomed Mater. 2019;98:26‐39. 10.1016/j.jmbbm.2019.04.052 PubMed DOI

Coathup MJ, Blunn GW, Mirhosseini N, et al. Controlled laser texturing of titanium results in reliable osteointegration. J Orthop Res. 2017;35(4):820‐828. 10.1002/jor.23340 PubMed DOI

Anitua E, Prado R, Orive G, Tejero R. Effects of calcium‐modified titanium implant surfaces on platelet activation, clot formation, and osseointegration. J Biomed Mater Res A. 2015;103(3):969‐980. 10.1002/jbm.a.35240 PubMed DOI

Wang G, Li J, Zhang W, et al. Magnesium ion implantation on a micro/nanostructured titanium surface promotes its bioactivity and osteogenic differentiation function. IJN. 2014;9(1):2387‐2398. 10.2147/IJN.S58357 PubMed DOI PMC

Sirin HT, Vargel I, Kutsal T, Korkusuz P, Piskin E. Ti implants with nanostructured and HA‐coated surfaces for improved osseointegration. Artif Cells Nanomed Biotechnol. 2016;44(3):1023‐1030. 10.3109/21691401.2015.1008512 PubMed DOI

Salduz A, Dikici F, Kılıçoğlu ÖI, et al. Effects of NSAIDs and hydroxyapatite coating on osseointegration. J Orthop Surg (Hong Kong). 2017;25(1):2309499016684410. 10.1177/2309499016684410 PubMed DOI

Epinette JA, Manley MT. Fifteen Years of Clinical Experience with Hydroxyapatite Coatings in Joint Arthroplasty. Paris, France: Springer‐Verlag; 2004. 10.1007/978-2-8178-0851-2 DOI

Chambers B, St Clair SF, Froimson MI. Hydroxyapatite‐coated tapered cementless femoral components in total hip arthroplasty. J Arthroplasty. 2007;22(4 suppl 1):71‐74. 10.1016/j.arth.2007.01.019 PubMed DOI

García‐Gareta E, Hua J, Orera A, Kohli N, Knowles JC, Blunn GW. Biomimetic surface functionalization of clinically relevant metals used as orthopaedic and dental implants. Biomed Mater. 2017;13(1):15008. 10.1088/1748-605X/aa87e6 PubMed DOI

Duvvuru MK, Han W, Chowdhury PR, Vahabzadeh S, Sciammarella F, Elsawa SF. Bone marrow stromal cells interaction with titanium; effects of composition and surface modification. PLoS One. 2019;14(5):e0216087. 10.1371/journal.pone.0216087 PubMed DOI PMC

Bello GD, Fouillen A, Badia A, Nanci A. A nanoporous titanium surface promotes the maturation of focal adhesions and formation of filopodia with distinctive nanoscale protrusions by osteogenic cells. Acta Biomater. 2017;60:339‐349. 10.1016/j.actbio.2017.07.022 PubMed DOI

Kwon Y‐S, Park J‐W. Osteogenic differentiation of mesenchymal stem cells modulated by a chemically modified super‐hydrophilic titanium implant surface. J Biomater Appl. 2018;33(2):205‐215. 10.1177/0885328218786873 PubMed DOI

Zhang H, Komasa S, Mashimo C, Sekino T, Okazaki J. Effect of ultraviolet treatment on bacterial attachment and osteogenic activity to alkali‐treated titanium with nanonetwork structures. Int J Nanomed. 2017;12:4633‐4646. 10.2147/IJN.S136273 PubMed DOI PMC

Chen P, Miyake M, Tsukamoto M, Tsutsumi Y, Hanawa T. Response of preosteoblasts to titanium with periodic micro/nanometer scale grooves produced by femtosecond laser irradiation. J Biomed Mater Res A. 2017;105(12):3456‐3464. 10.1002/jbm.a.36202 PubMed DOI

Zhukova Y, Hiepen C, Knaus P, et al. The role of titanium surface nanostructuring on preosteoblast morphology, adhesion, and migration. Adv Healthc Mater. 2017;6(15):1601244. 10.1002/adhm.201601244 PubMed DOI

He X, Zhang X, Bai L, et al. Antibacterial ability and osteogenic activity of porous Sr/Ag‐containing TiO2 coatings. Biomed Mater. 2016;11(4):45008. 10.1088/1748-6041/11/4/045008 PubMed DOI

Costa MM, Lima R, Melo‐Fonseca F, et al. Development of β‐TCP‐Ti6Al4V structures: driving cellular response by modulating physical and chemical properties. Korean J Couns Psychother. 2019;98:705‐716. 10.1016/j.msec.2019.01.016 PubMed DOI

Sola‐Ruiz MF, Perez‐Martinez C, Labaig‐Rueda C, Carda C, Martín De Llano JJ. Behavior of human osteoblast cells cultured on titanium discs in relation to surface roughness and presence of melatonin. Int J Mol Sci. 2017;18(44):823. 10.3390/ijms18040823 PubMed DOI PMC

Umeda H, Mano T, Harada K, Tarannum F, Ueyama Y. Appearance of cell–adhesion factor in osteoblast proliferation and differentiation of apatite coating titanium by blast coating method. J Mater Sci Mater Med. 2017;28(8):112. 10.1007/s10856-017-5913-8 PubMed DOI

Moussa M, Banakh O, Wehrle‐Haller B, et al. TiN x O y coatings facilitate the initial adhesion of osteoblasts to create a suitable environment for their proliferation and the recruitment of endothelial cells. Biomed Mater. 2017;12(2):25001. 10.1088/1748-605X/aa57a7 PubMed DOI

Li S, Yu W, Zhang W, Zhang G, Yu L, Lu E. Evaluation of highly carbonated hydroxyapatite bioceramic implant coatings with hierarchical micro‐/nanorod topography optimized for osseointegration. Int J Nanomed. 2018;13:3643‐3659. 10.2147/IJN.S159989 PubMed DOI PMC

Zhang W, Cao H, Zhang X, et al. A strontium‐incorporated nanoporous titanium implant surface for rapid osseointegration. Nanoscale. 2016;8(9):5291‐5301. 10.1039/c5nr08580b PubMed DOI

Coelho PG, Zavanelli RA, Salles MB, Yeniyol S, Tovar N, Jimbo R. Enhanced bone bonding to nanotextured implant surfaces at a short healing period: a biomechanical tensile testing in the rat femur. Implant Dent. 2016;25(3):322‐327. 10.1097/ID.0000000000000436 PubMed DOI

Jang I, Choi D‐S, Lee J‐K, Kim W‐T, Cha B‐K, Choi W‐Y. Effect of drug‐loaded TiO2 nanotube arrays on osseointegration in an orthodontic miniscrew: an in‐vivo pilot study. Biomed Microdevices. 2017;19(4):94. 10.1007/s10544-017-0237-5 PubMed DOI

Shaoki A, Xu J‐Y, Sun H, et al. Osseointegration of three‐dimensional designed titanium implants manufactured by selective laser melting. Biofabrication. 2016;8(4):45014. 10.1088/1758-5090/8/4/045014 PubMed DOI

Shah FA, Johansson ML, Omar O, Simonsson H, Palmquist A, Thomsen P. Laser‐modified surface enhances osseointegration and biomechanical Anchorage of commercially pure titanium implants for bone‐anchored hearing systems. PLoS One. 2016;11(6):e0157504. 10.1371/journal.pone.0157504 PubMed DOI PMC

Cohen DJ, Cheng A, Sahingur K, et al. Performance of laser sintered Ti‐6Al‐4V implants with bone‐inspired porosity and micro/nanoscale surface roughness in the rabbit femur. Biomed Mater. 2017;12(2):25021. 10.1088/1748-605X/aa6810 PubMed DOI PMC

Chappuis V, Maestre L, Bürki A, et al. Osseointegration of ultrafine‐grained titanium with a hydrophilic nano‐patterned surface: an in vivo examination in miniature pigs. Biomater Sci. 2018;6(9):2448‐2459. 10.1039/c8bm00671g PubMed DOI

Zhang M, Wang G‐L, Zhang H‐F, et al. Repair of segmental long bone defect in a rabbit radius nonunion model: comparison of cylindrical porous titanium and hydroxyapatite scaffolds. Artif Organs. 2014;38(6):493‐502. 10.1111/aor.12208 PubMed DOI

Velasco‐Ortega E, Ortiz‐García I, Jiménez‐Guerra A, et al. Comparison between sandblasted acid‐etched and oxidized titanium dental implants: in vivo study. Int J Mol Sci. 2019;20(13):3267. 10.3390/ijms20133267 PubMed DOI PMC

Zhou H‐Z, Li Y‐D, Liu L, et al. Early osseointegration of implants with cortex‐like TiO2 coatings formed by micro‐arc oxidation: a histomorphometric study in rabbits. J Huazhong Univ Sci Technol Med Sci. 2017;37(1):122‐130. 10.1007/s11596-017-1705-0 PubMed DOI

Pelegrine AA, Moy PK, Moshaverinia A, Escada ALDA, Calvo‐Guirado JL, Claro APRA. Development of a novel nanotextured titanium implant. An experimental study in rats. J Clin Med. 2019;8(7):954. 10.3390/jcm8070954 PubMed DOI PMC

Khosravi N, Maeda A, DaCosta RS, Davies JE. Nanosurfaces modulate the mechanism of peri‐implant endosseous healing by regulating neovascular morphogenesis. Commun Biol. 2018;1:72. 10.1038/s42003-018-0074-y PubMed DOI PMC

Ou K‐L, Hsu H‐J, Yang T‐S, Lin Y‐H, Chen C‐S, Peng P‐W. Osseointegration of titanium implants with SLAffinity treatment: a histological and biomechanical study in miniature pigs. Clin Oral Investig. 2016;20(7):1515‐1524. 10.1007/s00784-015-1629-7 PubMed DOI

Calciolari E, Mardas N, Dereka X, Anagnostopoulos AK, Tsangaris GT, Donos N. Protein expression during early stages of bone regeneration under hydrophobic and hydrophilic titanium domes. A pilot study. J Periodontal Res. 2018;53(2):174‐187. 10.1111/jre.12498 PubMed DOI

Gehrke SA, de Val Maté Sánchez JE, Fernández Domínguez M, de Aza Moya PN, Gómez Moreno G, Calvo Guirado JL. Effects on the osseointegration of titanium implants incorporating calcium‐magnesium: a resonance frequency and histomorphometric analysis in rabbit tibia. Clin Oral Implants Res. 2018;29(7):785‐791. 10.1111/clr.12909 PubMed DOI

Fan Y‐P, Chen X‐Y, Chen Y, Yang G‐L, Wang H‐M, He F‐M. Positive effect of strontium‐oxide layer on the osseointegration of moderately rough titanium surface in non‐osteoporotic rabbits. Clin Oral Implants Res. 2017;28(8):911‐919. 10.1111/clr.12897 PubMed DOI

Sartoretto SC, Alves ATNN, Zarranz L, Jorge MZ, Granjeiro JM, Calasans‐Maia MD. Hydrophilic surface of Ti6Al4V‐ELI alloy improves the early bone apposition of sheep tibia. Clin Oral Implants Res. 2017;28(8):893‐901. 10.1111/clr.12894 PubMed DOI

Dang Y, Zhang L, Song W, et al. In vivo osseointegration of Ti implants with a strontium‐containing nanotubular coating. Int J Nanomed. 2016;11:1003‐1011. 10.2147/IJN.S102552 PubMed DOI PMC

Kwon DH, Lee SJ, Wikesjö UME, Johansson PH, Johansson CB, Sul Y‐T. Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model. J Clin Periodontol. 2017;44(9):941‐949. 10.1111/jcpe.12776 PubMed DOI

Sharma A, McQuillan AJ, Shibata Y, Sharma LA, Waddell JN, Duncan WJ. Histomorphometric and histologic evaluation of titanium‐zirconium (aTiZr) implants with anodized surfaces. J Mater Sci Mater Med. 2016;27(5):86. 10.1007/s10856-016-5695-4 PubMed DOI

Tao Z‐S, Zhou W‐S, B‐l B, 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 Med. 2016;27(3):43. 10.1007/s10856-015-5650-9 PubMed DOI

Lee J‐B, Jo Y‐H, Choi J‐Y, et al. The effect of ultraviolet photofunctionalization on a titanium dental implant with machined surface: an in vitro and in vivo study. Materials (Basel). 2019;12(13):2078. 10.3390/ma12132078 PubMed DOI PMC

Park W, Ishijima M, Hirota M, Soltanzadeh P, Ogawa T. Engineering bone‐implant integration with photofunctionalized titanium microfibers. J Biomater Appl. 2016;30(8):1242‐1250. 10.1177/0885328215620034 PubMed DOI

Mistry S, Roy R, Kundu B, et al. Clinical outcome of hydroxyapatite coated, bioactive glass coated, and machined Ti6Al4V threaded dental implant in human jaws: a short‐term comparative study. Implant Dent. 2016;25(2):252‐260. 10.1097/ID.0000000000000376 PubMed DOI

Wang Z‐L, He R‐Z, Tu B, et al. Enhanced biocompatibility and osseointegration of calcium titanate coating on titanium screws in rabbit femur. J Huazhong Univ Sci Technol Med Sci. 2017;37(3):362‐370. 10.1007/s11596-017-1741-9 PubMed DOI

Su Y, Komasa S, Li P, et al. Synergistic effect of nanotopography and bioactive ions on peri‐implant bone response. Int J Nanomed. 2017;12:925‐934. 10.2147/IJN.S126248 PubMed DOI PMC

Galli S, Stocchero M, Andersson M, et al. The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation. Osteoporos Int. 2017;28(7):2195‐2205. 10.1007/s00198-017-4004-5 PubMed DOI PMC

Offermanns V, Andersen OZ, Riede G, et al. Bone regenerating effect of surface‐functionalized titanium implants with sustained‐release characteristics of strontium in ovariectomized rats. Int J Nanomed. 2016;11:2431‐2442. 10.2147/IJN.S101673 PubMed DOI PMC

Cardoso MV, de Rycker J, Chaudhari A, et al. Titanium implant functionalization with phosphate‐containing polymers may favour in vivo osseointegration. J Clin Periodontol. 2017;44(9):950‐960. 10.1111/jcpe.12736 PubMed DOI

Li K, Wang C, Yan J, et al. Evaluation of the osteogenesis and osseointegration of titanium alloys coated with graphene: an in vivo study. Sci Rep. 2018;8(1):1843. 10.1038/s41598-018-19742-y PubMed DOI PMC

Gurzawska K, Dirscherl K, Jørgensen B, Berglundh T, Jørgensen NR, Gotfredsen K. Pectin nanocoating of titanium implant surfaces—an experimental study in rabbits. Clin Oral Implants Res. 2017;28(3):298‐307. 10.1111/clr.12798 PubMed DOI

Ma T, Ge X‐Y, Hao K‐Y, et al. Simple 3,4‐dihydroxy‐l‐phenylalanine surface modification enhances titanium implant osseointegration in ovariectomized rats. Sci Rep. 2017;7(1):17849. 10.1038/s41598-017-18173-5 PubMed DOI PMC

Chen X, Zhou XC, Liu S, Wu RF, Aparicio C, Wu JY. In vivo osseointegration of dental implants with an antimicrobial peptide coating. J Mater Sci Mater Med. 2017;28(5):76. 10.1007/s10856-017-5885-8 PubMed DOI

Ilea A, Vrabie O‐G, Băbțan A‐M, et al. Osseointegration of titanium scaffolds manufactured by selective laser melting in rabbit femur defect model. J Mater Sci Mater Med. 2019;30(2):26. 10.1007/s10856-019-6227-9 PubMed DOI

Liu H, Zhou W, Ren N, et al. Cell sheets of co‐cultured endothelial progenitor cells and mesenchymal stromal cells promote osseointegration in irradiated rat bone. Sci Rep. 2017;7(1):3038. 10.1038/s41598-017-03366-9 PubMed DOI PMC

Puleo D. Understanding and controlling the bone–implant interface. Biomaterials. 1999;20(23–24):2311‐2321. 10.1016/s0142-9612(99)00160-x PubMed DOI

Study on Surface Roughness, Morphology, and Wettability of Laser-Modified Powder Metallurgy-Processed Ti-Graphite Composite Intended for Dental Application