Pure titanium and its alloys with good mechanical strength and biocompatibility,  are currently one of the commonly used permanent implants in clinical practice. However, the related in-fection caused by microorganisms will lead to the tissue around the titanium implant produce in-flammatory reactions, which may bring the risk of secondary operation for patients. The formation of bacterial biofilm on the surface of titanium implants, including the adhesion, reconstruction and mat-uration of bacterial colonies, is one of the main reasons of infection. Therefore, modifying the surface of titanium implants to inhibit the formation of bacterial biofilm is one of the effective ways to reduce postoperative infection caused by titanium implants. This method has attracted great interests in the field of orthopedics and dental implants. This paper first introduces the process of bacteria adhesion and maturation on the surface of implants, then summarizes the methods about surface modification and antibacterial mechanism of pure titanium and titanium alloy in detail. Finally, combining with the problems that haven’t been solved in the clinic anti-infection methods, the future development trend of titanium implants is discussed.

1.Geetha M, Singh AK, Asokamani R, et al. Ti based biomaterials, the ultimate choice for orthopaedic implants - a review[J]. Progress in Materials Science, 2009, 54(3): 397-425. DOI: 10.1016/j.pmatsci.2008.06.004.

2.崔振铎, 朱家民, 姜辉, 等. Ti及钛合金表面改性在生物医用领域的研究进展[J].金属学报, 2022, 58: 837-856. [Cui ZD, Zhu JM, Jiang H, et al. Research progress of the surface modification of titanium and titanium alloys for biomedical application[J]. Acta Metallurgica Sinica, 2022, 58: 837-856.] DOI: 10.11900/0412.1961.2022.00150.

3.Giraldo Giraldo V, Duque A, Aristizabal Aristizabal A, et al. Prevalence of peri-implant disease according to periodontal probing depth and bleeding on probing: a systematic review and meta-analysis[J]. Int J Oral Maxillofac Implants, 2018, 33(4): E89-E105. DOI: 10.11607/jomi.5940.

4.Costa RC, Nagay BE, Bertolini M, et al. Fitting pieces into the puzzle: The impact of titanium-based den-tal implant surface modifications on bacterial accumulation and polymicrobial infections[J]. Adv Colloid Interface Sci, 2021, 298: 102551. DOI: 10.1016/j.cis.2021.102551.

5.Karygianni L, Ren Z, Koo H, et al. Biofilm matrixome: extracellular components in structured microbial communities[J]. Trends Microbiol, 2020, 28(8): 668-681. DOI: 10.1016/j.tim.2020.03.016.

6.Grande R, Puca V, Muraro R. Antibiotic resistance and bacterial biofilm[J]. Expert Opin Ther Pat, 2020, 30(12): 897-900. DOI: 10.1080/13543776.2020.1830060.

7.Zhao Y, Li Y. Nanostructured titanium dioxide based on titanium alloys: synthesis and properties[J]. J Nanosci Nanotechnol, 2019, 19(1): 26-39. DOI: 10.1166/jnn.2019. 16440.

8.Huang R, Liu L, Li B, et al. Nanograins on Ti-25Nb-3Mo-2Sn-3Zr alloy facilitate fabricating biological surface through dual-ion implantation to concurrently modulate the osteogenic functions of mesen-chymal stem cells and kill bacteria[J]. J Mater Sci Technol, 2021, 73: 31-44. DOI: 10.1016/j.jmst.2020.07.048.

9.Chouirfa H, Bouloussa H, Migonney V, et al. Review of titanium surface modification techniques and coatings for antibacterial applications[J]. Acta Biomater, 2019, 83: 37-54. DOI: 10.1016/j.actbio.2018.10.036.

10.Xia C, Ma XH, Zhang XM, et al. Enhanced physicochemical and biological properties of C/Cu dual ions implanted medical titanium[J]. Bioact Mater, 2020, 5(2): 377-386. DOI: 10.1016/j.bioactmat.2020.02.017.

11.Yoshinari M, Oda Y, Kato T, et al. Influence of surface modifications to titanium on antibacterial activity in vitro[J]. Biomaterials, 2001, 22(14): 2043-2048. DOI: 10.1016/s0142-9612(00)00392-6.

12.Zheng L, Qian S, Liu XY. Induced antibacterial capability of TiO2 coatings in visible light via nitrogen ion implantation[J]. Transactions of Nonferrous Metals Society of China, 2020, 30(1): 171-180. DOI: 10.1016/s1003-6326(19)65189-7.

13.Han X, Ji XM, Zhao ML, et al. Mg/Ag ratios induced in vitro cell adhesion and preliminary antibacterial properties of TiN on medical Ti-6Al-4V alloy by Mg and Ag implantation[J]. Surface & Coatings Tech-nology, 2020, 397: 126020. DOI: 10.1016/j.surfcoat.2020.126020.

14.Jenkins J, Mantell J, Neal C, et al. Antibacterial effects of nanopillar surfaces are mediated by cell impedance, pene-tration and induction of oxidative stress[J]. Nat Commun, 2020, 11(1): 1626. DOI: 10.1038/s41467-020-15471-x.

15.Wang K, Jin HY, Song Q, et al. Titanium dioxide nanotubes as drug carriers for infection control and os-teogenesis of bone implants[J]. Drug Deliv Transl Res, 2021, 11(4): 1456-1474. DOI: 10.1007/s13346-021-00980-z.

16.Luo X, Yao SL, Zhang HJ, et al. Biocompatible nano-ripples structured surfaces induced by femtosecond laser to rebel bacterial colonization and biofilm formation[J]. Opt Laser Technol, 2020, 124: 105973. DOI: 10.1016/j.optlastec.2019.105973.

17.Ferraris S, Warchomicka F, Barberi J, et al. Contact guidance effect and prevention of microfouling on a beta titanium alloy surface structured by electron-beam technology[J]. Nanomaterials (Basel), 2021, 11(6): 1474. DOI: 10.3390/nano11061474.

18.Mansouri J, Truong VK, Maclaughlin S, et al. Polymerization-induced phase segregation and self-assembly of siloxane additives to provide thermoset coatings with a defined surface topology and biocidal and self-cleaning properties[J]. Nanomaterials (Basel), 2019, 9(11): 1610. DOI: 10.3390/nano9111610.

19.Ziegler N, Sengstock C, Mai V, et al. Glancing-angle deposition of nanostructures on an implant material surface[J]. Nanomaterials (Basel), 2019, 9(1): 60. DOI: 10.3390/nano9010060.

20.Elliott DT, Wiggins RJ, Dua R. Bioinspired antibacterial surface for orthopedic and dental implants[J]. J Biomed Mater Res Part B, 2021, 109(7): 973-981. DOI: 10.1002/jbm.b.34762.

21.Cui CX, Gao X, Qi YM, et al. Microstructure and antibacterial property of in situ TiO2 nanotube lay-ers/titanium biocomposites[J]. J Mech Behav Biomed Mater, 2012, 8: 178-183. DOI: 10.1016/j.jmbbm.2012.01.004.

22.Vishnu J, K Manivasagam V, Gopal V, et al. Hydrothermal treatment of etched titanium: a potential sur-face nano-modification technique for enhanced biocompatibility[J]. Nanomedicine, 2019, 20: 102016. DOI: 10.1016/j.nano. 2019.102016.

23.Galstyan V, Ponzoni A, Kholmanov I, et al. Highly sensitive and selective detection of dimethylamine through Nb-doping of TiO2 nanotubes for potential use in seafood quality control[J]. Sens Actuator B-Chem, 2020, 303: 127217. DOI: 10.1016/j.snb.2019.127217.

24.Linklater DP, Baulin VA, Juodkazis S, et al. Mechano-bactericidal actions of nanostructured surfaces[J]. Nat Rev Microbiol, 2021, 19(1): 8-22. DOI: 10.1038/s41579-020-0414-z.

25.Pogodin S, Hasan J, Baulin VA, et al. Biophysical model of bacterial cell interactions with nanopatterned cicada wing surfaces[J]. Biophys J, 2013, 104(4): 835-840. DOI: 10.1016/j.bpj.2012.12.046.

26.Xue FD, Liu JJ, Guo LF, et al. Theoretical study on the bactericidal nature of nanopatterned surfaces[J]. J Theor Biol, 2015, 385: 1-7. DOI: 10.1016/j.jtbi.2015.08.011.

27.Bandara CD, Singh S, Afara IO, et al. Bactericidal effects of natural nanotopography of dragonfly wing on escherichia coli[J]. ACS Appl Mater Interfaces, 2017, 9(8): 6746-6760. DOI: 10.1021/acsami.6b13666.

28.Cao YY, Su B, Chinnaraj S, et al. Nanostructured titanium surfaces exhibit recalcitrance towards Staphy-lococcus epidermidis biofilm formation[J]. Sci Rep, 2018, 8(1): 1071. DOI: 10.1038/s41598-018-19484-x.

29.Persat A. Bacterial mechanotransduction[J]. Curr Opin Microbiol, 2017, 36: 1-6. DOI: 10.1016/j.mib.2016.12.002.

30.Vassallo E, Pedroni M, Silvetti T, et al. Bactericidal performance of nanostructured surfaces by fluoro-carbon plasma[J]. Mater Sci Eng C Mater Biol Appl, 2017, 80: 117-121. DOI: 10.1016/j.msec.2017.05.111.

31.Modaresifar K, Azizian S, Ganjian M, et al. Bactericidal effects of nanopatterns: a systematic review[J]. Acta Biomater, 2019, 83: 29-36. DOI: 10.1016/j.actbio.2018. 09.059.

32.Shahali H, Hasan J, Cheng HH, et al. A systematic approach towards biomimicry of nanopatterned cica-da wings on titanium using electron beam lithography[J]. Nanotechnology, 2021, 32(6): 065301. DOI: 10.1088/13 61-6528/abbeaa.

33.Modaresifar K, Kunkels LB, Ganjian M, et al. Deciphering the roles of interspace and controlled disorder in the bactericidal properties of nanopatterns against staphylococcus aureus[J]. Nanomaterials (Basel), 2020, 10(2): 347. DOI: 10.3390/nano10020347.

34.Jenkins J, Ishak MI, Eales M, et al. Resolving physical interactions between bacteria and nanotopogra-phies with focused ion beam scanning electron microscopy[J]. Iscience, 2021, 24(7): 102818. DOI: 10.1016/j.isci.2021. 102818.

35.Gu YH, Liu HW, Dong XH, et al. Zwitterionic-phosphonate block polymer as anti-fouling coating for biomedical metals[J]. Rare Metals, 2022, 41(2): 700-712. DOI: 10.1007/s12598-021-01807-z.

36.Guo LL, Cheng YF, Ren X, et al. Simultaneous deposition of tannic acid and poly (ethylene glycol) to construct the antifouling polymeric coating on Titanium surface[J]. Colloids Surf B Biointerfaces, 2021, 200: 111592. DOI: 10.1016/j.colsurfb.2021.111592.

37.Gevrek TN, Yu K, Kizhakkedathu JN, et al. Thiol-reactive polymers for titanium interfaces: fabrication of antimicrobial coatings[J]. ACS Appl Polym Mater, 2019, 1(6): 1308-1316. DOI: 10.1021/acsapm.9b00117.

38.Nie BE, Long T, Li H, et al. A comparative analysis of antibacterial properties and inflammatory respons-es for the KR-12 peptide on titanium and PEGylated titanium surfaces[J]. Rsc Adv, 2017, 7(55): 34321-34330. DOI: 10.1039/c7ra05538b.

39.Liu JQ, Liu J, Attarilar S, et al. Nano-modified titanium implant materials: a way toward improved anti-bacterial properties[J]. Front Bioeng Biotechnol, 2020, 8: 576969. DOI: 10.3389/fbioe.2020.576969.

40.Camacho-Alonso F, Salinas J, Sanchez-Siles M, et al. Synergistic antimicrobial effect of photodynamic therapy and chitosan on the titanium-adherent biofilms of staphylococcus aureus, escherichia coli, and pseudomonas aeruginosa: an in vitro study[J]. J Periodontol, 2022, 93(6): e104-e115. DOI: 10.1002/JPER.21-0306.

41.Wang BB, Quan YH, Xu ZM, et al. Preparation of highly effective antibacterial coating with polydopa-mine/chitosan/silver nanoparticles via simple immersion[J]. Prog Org Coat, 2020, 149: 105967. DOI: 10.1016/j.porgcoat.2020.105967.

42.Fu XY, Liu X, Hao DZ, et al. Nickel-catcher-doped zwitterionic hydrogel coating on nickel-titanium alloy toward capture and detection of nickel ions[J]. Front Bioeng Biotechnol, 2021, 9: 698745. DOI: 10.3389/fbioe.2021. 698745.

43.张溪, 弓磊. 抗菌肽抗菌机制及研究热点[J].中国组织工程研究, 2020, 24(10): 1634-1640. [Zhang X, Gong L. Antimicrobial mechanism of antimicrobial peptide and research progress[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(10): 1634-1640.] DOI: 10.3969/j.issn.2095-4344.2202.

44.邓雪阳, 潘兰兰, 胡婷, 等. 钛合金表面氧化石墨烯涂层的制备[J].国际口腔医学杂志, 2018, 45: 539-545. [Deng XY, Pan LL, Hu T, et al. Preparation of graphene oxide coatings on titanium alloy surface[J]. International Journal of Stomatology, 2018, 45: 539-545.] DOI: 10.7518/gjkq.2018.05.008.

45.Ahmadabadi HY, Yu K, Kizhakkedathu JN. Surface modification approaches for prevention of implant associated infections[J]. Colloids Surf B Biointerfaces, 2020, 193: 111116. DOI: 10.1016/j.colsurfb.2020.111116.

46.Terada A, Okuyama K, Nishikawa M, et al. The effect of surface charge property on escherichia coli initial adhesion and subsequent biofilm formation[J]. Biotechnol Bioeng, 2012, 109(7): 1745-1754. DOI: 10.1002/bit.24429.

47.Dhall A, Islam S, Park M, et al. Bimodal nanocomposite platform with antibiofilm and self-powering func-tionalities for biomedical applications[J]. Acs Applied Materials & Interfaces, 2021, 13(34): 40379-40391. DOI: 10.1021/acsami.1c11791.

48.Shen J, Gao P, Han S, et al. A tailored positively-charged hydrophobic surface reduces the risk of im-plant associated infections[J]. Acta Biomater, 2020, 114: 421-430. DOI: 10.1016/j.actbio.2020.07.040.

49.Jin GD, Qin H, Cao HL, et al. Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium[J]. Biomaterials, 2014, 35(27): 7699-7713. DOI: 10.1016/j.biomaterials.2014.05.074.

50.Wang GM, Jin WH, Qasim AM, et al. Antibacterial effects of titanium embedded with silver nanoparticles based on electron-transfer-induced reactive oxygen species [J]. Biomaterials, 2017, 124: 25-34. DOI: 10.1016/j.biomaterials.2017.01.028.

51.Canty MK, Hansen LA, Tobias M, et al. Antibiotics enhance prevention and eradication efficacy of ca-thodic-voltage-controlled electrical stimulation against titanium-associated methicillin-resistant staph-ylococcus aureus and pseudomonas aeruginosa biofilms[J]. mSphere, 2019, 4(3): e00178-19. DOI: 10.1128/mSphere.00178-19.

52.Wang GM, Feng HQ, Hu LS, et al. An antibacterial platform based on capacitive carbon-doped TiO2 nanotubes after direct or alternating current charging[J]. Nat Commun, 2018, 9(1): 2055. DOI: 10.1038/s41467-018-04317-2.

53.Zheng Q, Shi BJ, Li Z, et al. Recent progress on piezoelectric and triboelectric energy harvesters in bio-medical systems[J]. Advanced Science, 2017, 4(7): 1700029. DOI: 10.1002/advs.201700029.

54.Shi R, Zhang JS, Tian JJ, et al. An effective self-powered strategy to endow titanium implant surface with associated activity of anti-biofilm and osteogenesis[J]. Nano Energy, 2020, 77: 105201. DOI: 10.1016/j.nanoen.2020.105201.

55.Zhang EL, Zhao XT, Hu JL, et al. Antibacterial metals and alloys for potential biomedical implants[J]. Bio-active Materials, 2021, 6(8): 2569-2612. DOI: 10.1016/j.bioac tmat.2021.01.030.

56.Zhuang YF, Ren L, Zhang SY, et al. Antibacterial effect of a copper-containing titanium alloy against im-plant-associated infection induced by methicillin-resistant Staphylococcus aureus[J]. Acta Biomater, 2021, 119: 472-484. DOI: 10.1016/j.actbio.2020.10.026.

57.Pan F, Altenried S, Zuber F, et al. Photo-activated titanium surface confers time dependent bactericidal activity towards gram positive and negative bacteria[J]. Colloids Surf B Biointerfaces, 2021, 206: 111940. DOI: 10.1016/j.colsurfb.2021.111940.

58.Xu N, Fu JJ, Zhao LZ, et al. Biofunctional elements incorporated nano/microstructured coatings on tita-nium implants with enhanced osteogenic and antibacterial performance[J]. Adv Healthc Mater, 2020, 9(23): e2000681. DOI: 10.1002/adhm.202000681.

59.Li YH, Yang Y, Li RY, et al. Enhanced antibacterial properties of orthopedic implants by titanium nano-tube surface modification: a review of current techniques[J]. Int J Nanomedicine, 2019, 14: 7217-7236. DOI: 10.2147/IJN.S216175.

60.韩涛, 郝建强, 李文波, 等. 抗生素骨水泥治疗骨关节感染的优势与问题[J]. 中国组织工程研究, 2023, 27: 470-477. [Han T, Hao JQ, Li WB, et al. Advantages and problems of antibiotic-loaded bone cements for bone and joint infections[J]. Chinese Journal of Tissue Engineering Research, 2023, 27: 470-477.] DOI: 10.12307/2023.034.

61.王婷婷, 孟存芳, 赵刚. 载银纳米二氧化钛对正畸釉质粘接剂抗菌性与粘接拉伸强度的影响[J].医学新知杂志, 2018, 28(1): 93-94. [Wang TT, Meng CF, Zhao G. Interpretation of the clinical pathway for transurethral plas-makinetic resection of bladder tumor[J]. New Medicine, 2018, 28(1): 93-94.] DOI: 10.3969/j.issn.1004- 5511.2018.01.032.

62.Roguska A, Belcarz A, Zalewska J, et al. Metal TiO2 nanotube layers for the treatment of dental implant infections[J]. Acs Applied Materials & Interfaces, 2018, 10(20): 17089-17099. DOI: 10.1021/acsami.8b04045.

63.Li B, Ma JW, Wang DH, et al. Self-adjusting antibacterial properties of Ag-incorporated nanotubes on micro-nanostructured Ti surfaces[J]. Biomater Sci, 2019, 7(10): 4075-4087. DOI: 10.1039/c9bm00862d.

64.Yin IX, Zhang J, Zhao IS, et al. The antibacterial mechanism of silver nanoparticles and its application in dentistry[J]. Int J Nanomedicine, 2020, 15: 2555-2562. DOI: 10.2147/ijn.S246764.

65.Hamlekhan A, Sinha-Ray S, Takoudis C, et al. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes[J]. Journal of Physics D-Applied Physics, 2015, 48(27): 275401. DOI: 10.1088/ 0022-3727/48/27/275401.

66.Yu YL, Ran QC, Shen XK, et al. Enzyme responsive titanium substrates with antibacterial property and osteo/angio-genic differentiation potentials[J]. Colloids Surf B Biointerfaces, 2020, 185: 110592. DOI: 10.1016/j.colsurfb.2019.110592.

67.Zhao JJ, Xu JW, Jian XX, et al. NIR light-driven photocatalysis on amphiphilic TiO2 nanotubes for control-lable drug release[J]. Acs Applied Materials & Interfaces, 2020, 12(20): 23606-23616. DOI: 10.1021/acsami.0c04260.

68.Qian WH, Qiu JJ, Su JS, et al. Minocycline hydrochloride loaded on titanium by graphene oxide: an ex-cellent antibacterial platform with the synergistic effect of contact-killing and release-killing[J]. Bio-mater Sci, 2018, 6(2): 304-313. DOI: 10.1039/c7bm00931c.

69.Palla-Rubio B, Araújo-Gomes N, Fernández-Gutiérrez M, et al. Synthesis and characterization of silica-chitosan hybrid materials as antibacterial coatings for titanium implants[J]. Carbohydr Polym, 2019, 203: 331-341. DOI: 10.1016/j.carbpol.2018.09.064.

70.Xu LC, Meyerhoff ME, Siedlecki CA. Blood coagulation response and bacterial adhesion to biomimetic polyurethane biomaterials prepared with surface texturing and nitric oxide release[J]. Acta Biomater, 2019, 84: 77-87. DOI: 10.1016/j.actbio.2018.11.035.

71.Sadrearhami Z, Shafiee FN, Ho KKK, et al. Antibiofilm nitric oxide-releasing polydopamine coatings[J]. ACS Appl Mater Interfaces, 2019, 11(7): 7320-7329. DOI: 10.1021/acsami.8b16853.