Introduction

In dental implantology, bacterial diseases of oral cavities, such as peri-implant mucositis and peri-implantitis, can result in loss of implants. Dental implants offer sub- and supragingivally located surfaces that are available to bacterial colonization. The microbiological findings show clearly that infection represents a possible etiological factor for late changes in implants ^1-3. Peri-implant mucositis, characterized by reversible inflammation of the soft tissues around the implant, can progress to peri-implantitis if left untreated. Peri-implantitis involves not only soft tissue inflammation but also bone resorption, leading to implant instability and potential loss ³. Beyond local effects, systemic consequences of bacterial translocation from the oral cavity are increasingly recognized. Bacteria that enter the bloodstream during dental procedures, including dental implant therapy, can potentially lead to severe systemic infections such as infective endocarditis ⁴.

Bacteria residing in biofilm such as anaerobic gram-negative species including Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia, along with facultative anaerobes like Staphylococcus aureus, are difficult to eliminate using systemic antibiotics. To address this challenge, various anti-adhesive and antimicrobial approaches have been developed to hinder the development of mature biofilms on biomaterial surfaces by minimizing or preventing the initial stages of bacterial attachment and colonization ⁵. It includes surface coatings with dendrimers or polymeric brushes, such as poly(ethylene glycol) layers ^6,7, surface modifications giving positive charges or turning the surface into a zwitterion layer ^8,9, titanium implant

Surface antimicrobial coatings encompass various types, such as ionic antibacterial layers, antibiotic or organic-based antimicrobial coatings, and substrates embedded with antibacterial compounds. Additionally, surface treatments utilizing silver nanoparticles or photocatalytic materials have also been used for antimicrobial purposes ⁵.

Titanium implant surface modifications can provide antimicrobial materials and offer a means to superimpose bacterial adhesion or biosynthesis by changing the surface wettability, texture, crystal morphology, surface potential and other characteristics ¹⁰.

The aim of this literature review is to explain the benefits of dental implant surface modifications acting on opportunistic microorganisms and pathogenic bacteria that can lead to an infection and thus to dental implant failure.

Materials and Methods

Scope: This review explores recent advancements in surface modification techniques for dental implants that enhance antimicrobial properties, including ionic antibacterial coating, antibiotics and organic antimicrobial coating and surface modifications, aiming to reduce bacterial adhesion and improve implant success.

Protocol development

Three authors (Y.R, M.V and D.G) used PICO system to formulate, present and answer the question: How

do the surface modifications of dental implants affect the antimicrobial properties in implant patients?

Participants (P): Patients receiving dental implants.

Intervention or Exposure and Comparison Group (IC): Surface modifications\coating of dental providing antimicrobial properties. Comparator: implants that did not go through surface modifications or coating prior implantation.

Outcome (O): Reduction in bacterial adhesion, colonization or biofilm formation.

Eligibility criteria

Inclusion criteria

Dental implantology

Publications in English

Antibacterial or anti-adhesive properties of the dental implant surface

Dental implant surface modification or coating

Exclusion criteria

No surface modification or coating

No relation to implantology

Search strategy

Two electronic databases were searched and information gathered from November 2 until December 17, 2024, as shown in table 1. In order to identify articles in the topic of interest, several related terms were used: “Dental implant surface modifications”, “Antimicrobial effect of dental implant surface coating” and “antimicrobial effect of dental implant surface modifications”.

Publications from 1974 up to 2024 in the interest topic were gathered, duplicates were removed manually, following which the titles and abstracts of the articles were screened independently based on the predefined inclusion and exclusion criteria.

Table 1: Electronic databases and search terms.

Data extraction

Relevant data were individually extracted from the selected articles by three reviewers (Y.R, M.V and D.G) using separate customized charts. Information such as authors' names, year of publication, and other data relevant to the topic were categorized and assessed within the charts. A condensed overview of the included studies is presented in Table 2, while the complete dataset, detailing all studies and their characteristics, is provided in the Supplementary Material (Table S1).

Table 2: Included study characteristics.

Results

A Flowchart was constructed using PRISMA flow diagram showing the identification, screening and selection of published materials for this review paper (see Appendix A).A total of 70 articles were found from electronic database search (PubMed and Google Scholar). Overall, 3 duplicates were removed, and 11 articles were excluded based on the inclusion and exclusion criteria. 56 publications were selected for abstract and full text analysis.

Ionic antibacterial coating

A total of 16 publications were selected for this review. Among them, five studies focused on silver coatings for implants, six on zinc coatings, three on copper coatings, and two on fluorine coatings. Additionally, four publications did not meet the inclusion criteria and were excluded. The implant is packaged in a sterile, air-tight container, with infections being rare due to strict medical device industry controls ¹⁰. Infections can arise from contaminated implant surfaces, surgical staff, the patient’s skin or mucosa, remote infections, contaminated disinfectants, or contact with others post-procedure ^11,12. Silver (Ag) is a powerful antimicrobial, acting through Ag+ ions or "contact killing," which disrupts bacterial cell walls and membranes, leading to cell death ^13,14. Techniques for silver antimicrobial coatings include plasma spraying and electrochemical deposition ⁹. Radtke et al. ¹⁵ developed a silver-doped titanium oxide nanotube coating, achieving 97.62% bacterial inhibition via hydroxyl radicals. Silver nanoparticles (AgNPs) enhance antimicrobial effects due to their large surface area and stable oxidative stress reactions ¹⁶. Zinc offers antimicrobial properties through ion, contact, and photocatalytic mechanisms, disrupting bacterial adhesion and membranes ^17-21. Wang et al. ²² developed a zinc-doped ZrO2/TiO2 coating with strong antimicrobial effects against Staphylococcus aureus and good biocompatibility. Copper has anti-inflammatory and antimicrobial properties and is safe at proper levels ²³. Jannesari et al. ²⁴ showed copper ions inhibit bacterial respiration and DNA. Fluorine, zinc, and copper can be added to titanium or hydroxyapatite coatings, with antimicrobial effects from gradual ion release ²⁵. Titanium tetrafluoride (TiF4) inhibits Streptococcus mutans and Bacteroides gingivalis on teeth ²⁶, and fluoride ions on titanium surfaces effectively combat peri-implantitis bacteria ²⁷.

Antibiotics and organic antimicrobial coating

In the context of antimicrobial coatings, 15 publications were included in the review. Of these, eight studies examined surface treatments using conventional antibiotics and antimicrobial peptides, five focused on dextran and polyethylene glycol (PEG), and two investigated chlorhexidine. One publication did not meet the inclusion criteria and was excluded. Conventional antibiotics are used in controlled release devices but can cause resistance due to an initial burst and prolonged sub- minimal inhibitory concentration (MIC) release ²⁵. To address this, antimicrobial peptides (AMPs) offer broad-spectrum activity and reduce resistance risks by binding to bacterial membranes and targeting intracellular components ^28-32. Various coating methods, including adsorption and electrospinning, help prevent bacterial colonization on implants ^33,34. Dextran and polyethylene glycol (PEG) coatings inhibit adhesion of proteins, platelets, and several types of bacteria ^35-38. Ion-implanted surfaces showed 55-80% fewer bacteria than pure titanium ³⁹. Chlorhexidine (CHX) is effective against gram-positive and gram-negative bacteria in oral care ⁴⁰. Wood et al. ⁴¹ developed a CHX nanoparticle coating with sustained antimicrobial effects against Streptococcus gordonii within 8 hours.

Surface modifications

Surface modifications emerged as the most extensively studied topic, with 25 publications included in this review. Among these, three studies explored surface treatments with titanium dioxide, three investigated ultraviolet (UV) treatment, four focused on surface roughness, six examined surface charge, three analyzed surface hydrophilicity, and six assessed the impact of surface crystalline phase on antimicrobial properties. Six publications were excluded for not meeting the inclusion criteria. Pure titanium forms a biocompatible and stable titanium dioxide (TiO2) layer in air, supporting osseointegration and offering antimicrobial properties under certain conditions ⁴². TiO2 nanotubes reduce bacterial adhesion after ultraviolet (UV) exposure, while TiO2 nanoparticles damage bacterial membranes via reactive oxygen species (ROS) ⁴³. TiO2 can also serve as a carrier for sustained drug release ⁹, and UV treatment decreases bacterial adhesion on implants ⁴⁴. Suketa et al. ⁴⁵ showed that an anatase TiO2 layer on titanium reduced Actinobacillus actinomycetemcomitans and Fusobacterium nucleatum viability to under 1% with ultraviolet A (UVA) exposure. UV-induced TiO2 photo-functionalization creates a super-hydrophilic surface that oxidizes organic impurities for antimicrobial effects ⁴⁶. Protein adsorption on implant surfaces is influenced by hydrophobicity, roughness, and chemical composition, affecting bacterial adhesion ^47-50. Bacteria often adhere to protein-coated surfaces, leading to biofilm formation through gene expression changes ^51-53. Combining biofilm-disrupting agents with antibiotics may improve outcomes, though this is rarely practiced due to chemical aggressiveness ⁵⁴. Surface smoothness reduces microbial colonization, but nano roughness can enhance protein adsorption and reduce bacterial adhesion ^5,54. Rough surfaces increases plaque accumulation in dentistry ⁵⁵. Techniques like ion implantation, laser cladding, and anodizing create nano-scale structures ^56,57. Surface charge and hydrophilicity affect bacterial adhesion; negatively charged and hydrophilic surfaces generally reduce bacterial attachment ^51,52,57,58. Bacterial adhesion depends on electrostatic interactions and substrate-bacteria physicochemical properties ⁵⁹. Gao et al. ⁶⁰ linked antibacterial effects to electrostatic disturbances causing cell death. Hydrophobic interactions drive adhesion of pathogens like Streptococcus aureus and Staphylococcus epidermidis ^61,62. TiO2’s crystalline forms like anatase, rutile, and brookite, all contribute to antibacterial properties through photocatalytic activity (PCA) ^54,64-66.

Across all modalities, ion-based coating provided the strongest broad-spectrum antimicrobial effect. Peptide-based coating showed excellent biofilm prevention with a low risk for antibiotic resistance. Surface roughness and charge modification improved early bacterial suppression but required combination with other modalities for stronger antimicrobial performance.

Discussion

Dental implant infections are a rare but serious complication that can arise from various sources, including contaminated implant surfaces, surgical staff, or the patient’s own skin. Silver is highly effective in combating microbial contamination through ion release or direct contact killing, and silver-based coatings, including silver nanoparticles, have been developed for enhanced antimicrobial activity. Similarly, other metals like zinc and copper exhibit strong antimicrobial properties through various mechanisms, with some coatings also maintaining biocompatibility. Antimicrobial peptides offer a promising alternative to antibiotics, as they exhibit broad-spectrum activity and are less prone to inducing bacterial resistance. Titanium dioxide, commonly used in implants for its biocompatibility and photocatalytic properties, can also be utilized to reduce bacterial adhesion, especially under ultraviolet light. Furthermore, surface modifications such as nanopatterning and doping with antimicrobial agents can significantly reduce bacterial colonization and biofilm formation, thereby improving the longevity and safety of dental implants.

Ionic antibacterial coating

Silver (Ag) stands out as the most potent metal against microbes, exerting its antibacterial activity either through the release of Ag+ ions or by directly destroying microorganisms upon contact ^13,14. Various techniques have been developed to create silver-containing antimicrobial coatings, including plasma spraying, electrochemical deposition, sol-gel processes, thermal spraying, co-sputtering, and plasma immersion ion implantation ⁹. Radtke A et al. ¹⁵ developed a silver-doped titanium oxide nanotube array coating by immersing the substrate in a silver nitrate solution. This modification effectively suppressed biofilm formation Silver nanoparticles (AgNPs) have also been recognized as a promising alternative for silver-based antimicrobial coatings. AgNPs provide long-lasting and stable antimicrobial activity through oxidative stress mechanisms and the generation of reactive oxygen species¹⁶. Similar to silver, zinc exerts its antimicrobial properties through the three mechanisms earlier described ^17-19. Wang et al. ²² developed a zinc-doped ZrO2/TiO2 coating on a Titanium/Aluminum/Vanadium alloy (Ti6Al4V) surface using a combination of magnetron sputtering and microarc oxidation. This coating demonstrated exceptional antimicrobial effectiveness against Staphylococcus aureus while maintaining biocompatibility and corrosion resistance. Copper is an inexpensive and readily available metal that has been utilized since ancient times, both in its pure form and as metal compounds, for its anti-inflammatory, antimicrobial, and anti-proliferative properties ²³. At appropriate levels, copper is non-toxic to humans. Research by Jannesari et al. ²⁴ indicated that copper ions and their superoxide derivatives can disrupt bacterial respiratory processes and cause degradation of bacterial DNA, thus providing significant antimicrobial effects. Elements such as fluorine (F), zinc (Zn), and copper (Cu) can be integrated into titanium or hydroxyapatite coatings through anodic oxidation of their respective ions. The bactericidal action of these ions appears to rely on their gradual release into the surrounding environment, with one proposed mechanism for bacteriostasis being the hydroxylation into highly reactive components ²⁵. In vitro study by Skartveit et al. ²⁶ demonstrated that titanium tetrafluoride (TiF4) effectively inhibits the proliferation of Streptococcus mutans and Bacteroides gingivalis on tooth surfaces. Meanwhile, Yoshinari et al. ²⁷ successfully introduced fluoride ions to the surface of pure titanium using ion accelerators, achieving effective inhibition of pathogenic bacteria associated with peri-implantitis.

Antibiotics and organic antimicrobial coating

Conventional drug studies have utilized antibiotics such as amoxicillin, vancomycin, gentamicin, tetracycline, minocycline, and cephalothin, incorporated into controlled-release systems. A major issue with these antibiotics is the initial burst release, which is often followed by a sustained release at levels below the MIC, potentially promoting the development of bacterial resistance over time ²⁵. Due to their tendency to promote drug resistance, the use of antibiotics is limited, whereas the development of AMPs offers a new strategy to address this challenge ²⁸. AMPs are short amphiphilic peptides with broad-spectrum antimicrobial activity. Their positive charge allows them to interact with negatively charged bacterial membranes via electrostatic attraction, ultimately resulting in bacterial cell death ^29,30. Research has shown that AMPs can penetrate the bacterial cytoplasm to target intracellular components such as DNA, RNA, and proteins, thereby killing bacteria from within and affecting gene expression ^31,32. Due to their unique antibacterial mechanisms, bacteria find it challenging to develop resistance. Various methods have been employed to coat antimicrobial peptides onto implant surfaces to prevent bacterial colonization, including adsorption, binding, electrospinning, and chemical attachment ^33,34. Dextran and polyethylene glycol (PEG) surfaces have proven effective at inhibiting protein adhesion, platelet adhesion, bacterial adhesion, and biofilm formation by oral pathogens such as Staphylococcus aureus, Streptococcus sanguinis, Lactobacillus salivarius, Streptococcus mutans, and Streptococcus gordonii ^35-38. Bacterial counts on ion-implanted surfaces decreased significantly compared to pure titanium ³⁹. Chlorhexidine (CHX) is a widely utilized surface disinfectant known for its effectiveness against both gram-positive and gram-negative bacteria. Consequently, it is frequently employed for local cleaning and disinfection during oral surgical procedures and oral care ⁴⁰. Wood et al. ⁴¹ developed a chlorhexamethy hexameta-phosphate nanoparticle coating on pure titanium, with an average particle diameter of 49 nm. This coating demonstrated sustained release of CHX and exhibited antimicrobial activity against the oral primary colonizing bacterium Streptococcus gordonii within 8 hours.

Surface modifications

Pure titanium rapidly develops a thin layer of titanium dioxide (TiO2) when exposed to air, which exhibits excellent biocompatibility and chemical stability. Additionally, TiO2 possesses antimicrobial properties under certain conditions ⁴². For instance, TiO2 nanotubes can significantly inhibit bacterial adhesion post-ultraviolet radiation exposure, while TiO2 nanoparticles can damage bacterial membranes by generating ROS ⁴³. Furthermore, TiO2 can act as a carrier for antimicrobial drugs, allowing for their sustained release from the metal ⁹. Bacterial adhesion and polymerization on implant surfaces significantly decreased after 8 hours of UV treatment ⁴⁴. In research conducted by Suketa et al. ⁴⁵, a thin layer of photocatalytic anatase TiO2 was applied to the surface of pure titanium via plasma source ion implantation followed by annealing. This layer demonstrated a robust photocatalytic reaction under UVA illumination, suppressing the viability of both Actinobacillus actinomycetemcomitans and Fusobacterium nucleatum to less than 1% under UVA exposure within 120 minutes. The UV light-induced photo-functionalization of TiO2 eliminates hydrocarbon contamination and results in a super-hydrophilic surface that oxidizes adsorbed organic impurities. This secondary oxidation, initiated by ROS, is believed to be essential for achieving antimicrobial activity ⁴⁶.  Protein adsorption is influenced by several factors, including surface hydrophobicity, roughness, porosity, chemical composition, as well as the composition and concentration of the protein solution, salt concentrations, and pH ^47-50. The layer of adsorbed proteins is crucial for bacterial adhesion. In reality, bacteria rarely encounter a "clean" surface on an implant. Free-swimming bacteria, in the so-called planktonic state, tend to adhere to these surface-adsorbed proteins ^51,52. The adhered bacteria can proliferate and attract other bacteria from the surrounding environment. Once a sufficient population of bacteria forms a colony on the surface, they will modify their gene expression patterns. Genes responsible for producing extracellular polymeric substances, vital for biofilm formation, will be activated and expressed ^52,53. The combined use of biofilm-disrupting agents alongside antibiotics appears to be a more effective strategy; however, this approach is not frequently implemented in practice due to the aggressive nature of the chemicals involved ⁵². It is evident that the topological and chemical properties of a dental implant surface significantly influence the adhesion rate of microorganisms. A completely smooth surface is less prone to microbial colonization compared to a rough surface, which provides a larger area for adhesion and greater adhesive forces generated by microorganisms per unit area ⁵. Although, Puckett et al. ⁵⁴ noted that surfaces with increased nano roughness exhibit higher surface energy, leading to enhanced protein adsorption and, consequently, reduced bacterial adhesion. However, specific threshold values regarding surface roughness that may affect bacterial adhesion remain undefined. In the field of dentistry, a rise in plaque accumulation has been observed with roughness measurements exceeding 0.2 um ⁵⁵. Various methods are utilized to create nano-scale structures on implant surfaces. Zhang et al. ⁵⁶ successfully produced a silver-zinc oxide-hydroxyapatite (Ag-ZnO-HA) nanocomposite on Ti6Al4V using laser cladding, which demonstrated excellent antibacterial properties against Escherichia coli and Streptococcus aureus in vitro, along with favorable osteogenesis properties in vivo. Most microorganisms possess a charged outer membrane and contain hydrophobic regions, which may contribute to their adhesion to the hydrophobic surfaces of medical implants. Nonetheless, the adhesion of microorganisms typically relies on the formation of a protein layer on the surface, potentially revealing high-affinity adhesion sites ^51,52. Negatively charged surfaces tend to be less prone to bacterial adhesion than positively charged surfaces, as most bacteria have negatively charged cell walls ^57,58. The effect of electrical repulsion on bacterial adhesion becomes more pronounced with increased surface hydrophilicity. In terms of surface free energy, the degree of bacterial adhesion can either rise or fall with increasing surface energy of substrates, depending on the physicochemical characteristics of both the substrate and the bacterial strains involved, as well as the aqueous solution utilized ⁵⁹. Gao et al. ⁶⁰ found that the antibacterial effect observed on the studied surface resulted from electrostatic disturbances that triggered autolytic and/or cellular death mechanisms. Surface hydrophilicity contributes to the interactions between biomaterials and bacteria, but these systems are complex and shaped by various factors, including the implant location and the specific bacterial species and strains involved. Theoretically, hydrophobic bacterial strains are more likely to adhere to biomaterials with hydrophobic characteristics, while hydrophilic species are inclined to attach to hydrophilic surfaces ⁶¹. Hydrophobic interactions are common and play a role in the mechanisms of various microbial adhesion factors, including hydrophobic components of cell membranes and adhesins found on fimbriae or pili ⁶². Research has confirmed that the adhesion of human pathogens such as Streptococcus aureus and Staphylococcus epidermidis correlates with increased hydrophobicity of the biomaterial surface, establishing hydrophobicity as a primary driver of bacterial adhesion ⁶³. Concerning the crystalline phases of the surface, titanium dioxide can exist in three forms. The crystalline structure is closely linked to its ability to inhibit bacterial adherence ^54,64,65. All three forms exhibit photocatalytic activity, which contribute to their antibacterial properties ^61,64,66.

All included studies were published in English, which may introduce language bias and limit of the findings. The review primarily focused on in vitro and some in vivo studies, which may not fully reflect clinical outcomes in human subjects. Furthermore, variations in study design, methodologies, and outcome measures among the reviewed studies could impact the consistency and comparability of the results.

Conclusions

This review highlights the critical role of surface modifications and antimicrobial coatings in reducing infections in dental implants. Materials like silver, zinc, copper, and fluorine exhibit strong antimicrobial properties, preventing bacterial growth through ion release, oxidative stress, and photocatalytic activity. Additionally, surface characteristics such as roughness, charge, and crystalline phase significantly influence bacterial adhesion, underscoring the need for optimized implant surface designs. Ultraviolet treatment and titanium dioxide coatings further enhance antimicrobial effects, with titanium dioxide generating reactive oxygen species to disrupt bacterial membranes. Other strategies, including chlorhexidine coatings and controlled-release antibiotic devices, offer infection control but face challenges like bacterial resistance. Meanwhile, alternatives such as dextran and polyethylene glycol coatings effectively reduce biofilm formation and bacterial adhesion, presenting promising solutions for implant-related infections. Despite these advancements, further research is essential to evaluate the long-term stability and performance of these coatings, particularly under different clinical conditions.

Acknowledgement

The authors thank the School of Dental Medicine, University of Zagreb, for institutional support and Dr. Vadim Reiser for his valuable guidance during the preparation of this review.

Funding Sources

The research was funded as part of the project 'Evaluation of Innovative and Standard Protocols in Endodontic and Surgical Therapy', no. SFZG-05- 2025, INOENDO, co-financed from the funds of the National Recovery and Resilience Plan (NRRP).

Conflict of Interest

The authors do not have any conflict of interest.

Authors’ Contribution

Y.R. (Yuval Reiser): Conceptualization, Methodology, Investigation, Writing – Original Draft, Writing-Review and Editing.

M.V. (Marko Vuletic): Software, Validation, Data Curation, Writing – Original Draft, Writing-Review and Editing.

D.G. (Dragana Gabric): Conceptualization, Visualization, Supervision, Validation, Project Administration, Writing-Review and Editing.

References

1. Pye AD, Lockhart DE, Dawson MP, Murray CA, Smith AJ. A review of dental implants and infection. J Hosp Infect. 2009;72(2):104–110. doi:10.1016/j.jhin.2009.02.010
   CrossRef
2. Norowski PA Jr, Bumgardner JD. Biomaterial and antibiotic strategies for peri-implantitis: a review. J Biomed Mater Res B Appl Biomater. 2009;88(2):530–543. doi:10.1002/jbm.b.31152
   CrossRef
3. Esposito M, Hirsch JM, Lekholm U, Thomsen P. Biological factors contributing to failures of osseointegrated oral implants. (II). Etiopathogenesis. Eur J Oral Sci. 1998;106(3):721–764. doi:10.1046/j.0909-8836.1998.t01-6-.x
   CrossRef
4. Kerrigan SW, Cox D. Platelet-bacterial interactions. Cell Mol Life Sci. 2009;67(4):513–523. doi:10.1007/s00018-009-0207-z
   CrossRef
5. Knetsch MLW, Koole LH. New strategies in the development of antimicrobial coatings: the example of increasing usage of silver and silver nanoparticles. Polymers (Basel). 2011;3(1):340–366. doi:10.3390/polym3010340
   CrossRef
6. Eichler M, Katzur V, Scheideler L, et al. The impact of dendrimer-grafted modifications to model silicon surfaces on protein adsorption and bacterial adhesion. Biomaterials. 2011;32(38):9168–9179. doi:10.1016/j.biomaterials.2011.08.063
   CrossRef
7. Müller R, Eidt A, Hiller KA, et al. Influences of protein films on antibacterial or bacteria-repellent surface coatings in a model system using silicon wafers. Biomaterials. 2009;30(29):4921–4929. doi:10.1016/j.biomaterials.2009.05.079
   CrossRef
8. Roosjen A, Norde W, van der Mei HC, Busscher HJ. The use of positively charged or low surface free energy coatings versus polymer brushes in controlling biofilm formation. In: Grundke K, Stamm M, Adler HJ, eds. Characterization of Polymer Surfaces and Thin Films. Springer; 2009:132. doi:10.1007/2882_026
   CrossRef
9. Zheng TX, Li W, Gu YY, Zhao D, Qi MC. Classification and research progress of implant surface antimicrobial techniques. J Dent Sci. 2022;17(1):1–7. doi:10.1016/j.jds.2021.08.019
   CrossRef
10. Young WT. How to respond to changes in the regulation of the ethylene-oxide sterilization process. Med Device Technol. 2004;17(3):12–15. PMID:16736657
11. Rosenthal VD, Yin R, Nercelles P, et al. International Nosocomial Infection Control Consortium (INICC) report of healthcare-associated infections, data summary of 45 countries for 2015 to 2020, adult and pediatric units, device-associated module. Am J Infect Control. 2024;52(9):1002–1011. doi:10.1016/j.ajic.2023.12.019
    CrossRef
12. Bearman GM, Munro C, Sessler CN, Wenzel RP. Infection control and the prevention of nosocomial infections in the intensive care unit. Semin Respir Crit Care Med. 2006;27(3):310–324. doi:10.1055/s-2006-945534
    CrossRef
13. Wei X, Li Q, Wu C, Sun T, Li X. Preparation, characterization, and antibacterial mechanism of the chitosan coatings modified by Ag/ZnO microspheres. J Sci Food Agric. 2020;100(13):5527–5538. doi:10.1002/jsfa.10605
    CrossRef
14. Bui VD, Mwangi JW, Schubert A. Powder mixed electrical discharge machining for antibacterial coating on titanium implant surfaces. J Manuf Process. 2019;44:261–270. doi:10.1016/j.jmapro.2019.05.032
    CrossRef
15. Radtke A, Topolski A, Jedrzejewski T, et al. The bioactivity and photocatalytic properties of titania nanotube coatings produced with the use of the low-potential anodization of Ti6Al4V alloy surface. Nanomaterials (Basel). 2017;7(8):197. doi:10.3390/nano7080197
    CrossRef
16. Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The antibacterial mechanism of silver nanoparticles and its application in dentistry. Int J Nanomedicine. 2020;15:2555–2562. doi:10.2147/IJN.S246764
    CrossRef
17. de Lima CO, de Oliveira ALM, Silva Filho EC, et al. Zn-doped mesoporous hydroxyapatites and their antimicrobial properties. Colloids Surf B Biointerfaces. 2020;198:111471. doi:10.1016/j.colsurfb.2020.111471
    CrossRef
18. Maimaiti B, Zhang N, Yan L, et al. Stable ZnO-doped hydroxyapatite nanocoating for anti-infection and osteogenic properties on titanium. Colloids Surf B Biointerfaces. 2019;186:110731. doi:10.1016/j.colsurfb.2019.110731
    CrossRef
19. Padmavathy N, Vijayaraghavan R. Enhanced bioactivity of ZnO nanoparticles—an antimicrobial study. Sci Technol Adv Mater. 2008;9(3):035004. doi:10.1088/1468-6996/9/3/035004
    CrossRef
20. Memarzadeh K, Sharili AS, Huang J, Rawlinson SC, Allaker RP. Nano-particulate zinc oxide as a coating material for orthopedic and dental implants. J Biomed Mater Res A. 2015;103(3):981–989. doi:10.1002/jbm.a.35241
    CrossRef
21. Liu Y, He L, Mustapha A, Li H, Hu ZQ, Lin M. Antibacterial activities of zinc oxide nanoparticles against Escherichia coli O157:H7. J Appl Microbiol. 2009;107(4):1193–1201. doi:10.1111/j.1365-2672.2009.04303.x
    CrossRef
22. Wang R, He X, Gao Y, Zhang X, Yao X, Tang B. Antimicrobial property, cytocompatibility, and corrosion resistance of Zn-doped ZrO₂/TiO₂ coatings on Ti6Al4V implants. Mater Sci Eng C Mater Biol Appl. 2017;75:7–15. doi:10.1016/j.msec.2017.02.036
    CrossRef
23. Li Y, Liu L, Wan P, et al. Biodegradable Mg-Cu alloy implants with antibacterial activity for the treatment of osteomyelitis: in vitro and in vivo evaluations. Biomaterials. 2016;106:250–263. doi:10.1016/j.biomaterials.2016.08.031
    CrossRef
24. Jannesari M, Akhavan O, Madaah Hosseini HR, Bakhshi B. Graphene/CuO₂ nanoshuttles with controllable release of oxygen nanobubbles promoting interruption of bacterial respiration. ACS Appl Mater Interfaces. 2020;12(32):35813–35825. doi:10.1021/acsami.0c05732
    CrossRef
25. Grischke J, Eberhard J, Stiesch M. Antimicrobial dental implant functionalization strategies: a systematic review. Dent Mater J. 2016;35(4):545–558. doi:10.4012/dmj.2015-314
    CrossRef
26. Skartveit L, Selvig KA, Myklebust S, Tveit AB. Effect of TiF₄ solutions on bacterial growth in vitro and on tooth surfaces. Acta Odontol Scand. 2017;48(3):169–174. doi:10.3109/00016359009005872
    CrossRef
27. Yoshinari M, Oda Y, Kato T, Okuda K. Influence of surface modifications to titanium on antibacterial activity in vitro. Biomaterials. 2001;22(14):2043–2048. doi:10.1016/S0142-9612(00)00392-6
    CrossRef
28. Zhang E, Zhao X, Hu J, Wang R, Fu S, Qin G. Antibacterial metals and alloys for potential biomedical implants. Bioact Mater. 2021;6(8):2569–2612. doi:10.1016/j.bioactmat.2021.01.030
    CrossRef
29. Lozeau LD, Rolle MW, Camesano TA. A QCM-D study of the concentration- and time-dependent interactions of human LL37 with model mammalian lipid bilayers. Colloids Surf B Biointerfaces. 2018;167:229–238. doi:10.1016/j.colsurfb.2018.04.016
    CrossRef
30. Sun H, Hong Y, Xi Y, Zou Y, Gao J, Du J. Synthesis, self-assembly, and biomedical applications of antimicrobial peptide–polymer conjugates. Biomacromolecules. 2018;19(6):1701–1720. doi:10.1021/acs.biomac.8b00208
    CrossRef
31. Geng H, Yuan Y, Adayi A, Zhang X, Song X, Gong L, Zhang X, Gao P. Engineered chimeric peptides with antimicrobial and titanium-binding functions to inhibit biofilm formation on Ti implants. Mater Sci Eng C Mater Biol Appl. 2017;82:141–154. doi:10.1016/j.msec.2017.08.062
    CrossRef
32. Wang M, Tang T. Surface treatment strategies to combat implant-related infection from the beginning. J Orthop Translat. 2018;17:42–54. doi:10.1016/j.jot.2018.09.001
    CrossRef
33. Garaicoa JL, Bates AM, Avila-Ortiz G, Brogden KA. Antimicrobial prosthetic surfaces in the oral cavity: a perspective on creative approaches. Microorganisms. 2020;8(8):1247. doi:10.3390/microorganisms8081247
    CrossRef
34. Tiwari A, Sharma P, Vishwamitra B, Singh G. Review on surface treatment for implant infection via gentamicin and antibiotic-releasing coatings. Coatings. 2021;11(8):1006. doi:10.3390/coatings11081006
    CrossRef
35. Shi Z, Neoh KG, Kang ET, Poh CK, Wang W. Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration. Biomacromolecules. 2009;10(6):1603–1611. doi:10.1021/bm900203w
    CrossRef
36. Tanaka Y, Matin K, Gyo M, Okada A, Tsutsumi Y, Doi H, Nomura N, Tagami J, Hanawa T. Effects of electrodeposited poly(ethylene glycol) on biofilm adherence to titanium. J Biomed Mater Res A. 2010;95(4):1105–1113. doi:10.1002/jbm.a.32932
    CrossRef
37. Bozzini S, Petrini P, Tanzi MC, Arciola CR, Tosatti S, Visai L. Poly(ethylene glycol) and hydroxy-functionalized alkane phosphate self-assembled monolayers reduce bacterial adhesion and support osteoblast proliferation. Int J Artif Organs. 2011;34(9):898–907. doi:10.5301/ijao.5000047
    CrossRef
38. Harris LG, Tosatti S, Wieland M, Textor M, Richards RG. Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers. Biomaterials. 2004;25(18):4135–4148. doi:10.1016/j.biomaterials.2003.11.033
    CrossRef
39. Ge X, Leng Y, Bao C, Xu SL, Wang R, Ren F. Antibacterial coatings of fluoridated hydroxyapatite for percutaneous implants. J Biomed Mater Res A. 2010;95(2):588–599. doi:10.1002/jbm.a.32862
    CrossRef
40. Gjermo P. Chlorhexidine in dental practice. J Clin Periodontol. 1974;1(3):143–152. doi:10.1111/j.1600-051x.1974.tb01250.x
    CrossRef
41. Wood NJ, Jenkinson HF, Davis SA, Mann S, O’Sullivan DJ, Barbour ME. Chlorhexidine hexametaphosphate nanoparticles as a novel antimicrobial coating for dental implants. J Mater Sci Mater Med. 2015;26(6):201. doi:10.1007/s10856-015-5532-1
    CrossRef
42. Cui CX, Gao X, Qi YM, Liu SJ, Sun JB. Microstructure and antibacterial property of in situ TiO₂ nanotube layers/titanium biocomposites. J Mech Behav Biomed Mater. 2012;8:178–183. doi:10.1016/j.jmbbm.2012.01.004
    CrossRef
43. Ranjan S, Ramalingam C. Titanium dioxide nanoparticles induce bacterial membrane rupture by reactive oxygen species generation. Environ Chem Lett. 2016;14(4):487–494. doi:10.1007/s10311-016-0586-y
    CrossRef
44. Yamada Y, Yamada M, Ueda T, Sakurai K. Reduction of biofilm formation on titanium surface with ultraviolet-C pre-irradiation. J Biomater Appl. 2014;29(2):161–171. doi:10.1177/0885328213518085
    CrossRef
45. Suketa N, Sawase T, Kitaura H, Naito M, Baba K, Nakayama K, Wennerberg A, Atsuta M. An antibacterial surface on dental implants based on the photocatalytic bactericidal effect. Clin Implant Dent Relat Res. 2005;7(2):105–111. doi:10.1111/j.1708-8208.2005.tb00053.x
    CrossRef
46. Shibata Y, Suzuki D, Omori S, Tanaka R, Murakami A, Kataoka Y, Baba K, Kamijo R, Miyazaki T. Characteristics of in vitro biological activity of titanium surfaces anodically oxidized in chloride solutions. Biomaterials. 2010;31(33):8546–8555. doi:10.1016/j.biomaterials.2010.07.098
    CrossRef
47. Thevenot P, Hu W, Tang L. Surface chemistry influences implant biocompatibility. Curr Top Med Chem. 2008;8(4):270–280. doi:10.2174/156802608783790901
    CrossRef
48. Vroman L. Methods of investigating protein interactions on artificial and natural surfaces. Ann N Y Acad Sci. 1987;516:300–305. doi:10.1111/j.1749-6632.1987.tb33050.x
    CrossRef
49. Stutz H. Protein attachment onto silica surfaces: a survey of molecular fundamentals, resulting effects and novel preventive strategies in CE. Electrophoresis. 2009;30(12):2032–2061. doi:10.1002/elps.200900015
    CrossRef
50. Fang F, Szleifer I. Kinetics and thermodynamics of protein adsorption: a generalized molecular theoretical approach. Biophys J. 2001;80(6):2568–2589. doi:10.1016/S0006-3495(01)76228-5
    CrossRef
51. Pavithra D, Doble M. Biofilm formation, bacterial adhesion and host response on polymeric implants: issues and prevention. Biomed Mater. 2008;3(3):034003. doi:10.1088/1748-6041/3/3/034003
    CrossRef
52. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010;35(4):322–332. doi:10.1016/j.ijantimicag.2009.12.011
    CrossRef
53. Hall-Stoodley L, Stoodley P. Evolving concepts in biofilm infections. Cell Microbiol. 2009;11(7):1034–1043. doi:10.1111/j.1462-5822.2009.01323.x
    CrossRef
54. Puckett SD, Taylor E, Raimondo T, Webster TJ. The relationship between the nanostructure of titanium surfaces and bacterial attachment. Biomaterials. 2010;31(4):706–713. doi:10.1016/j.biomaterials.2009.09.081
    CrossRef
55. Bollen CM, Lambrechts P, Quirynen M. Comparison of surface roughness of oral hard materials to the threshold surface roughness for bacterial plaque retention: a review. Dent Mater. 1997;13(4):258–269. doi:10.1016/S0109-5641(97)80038-3
    CrossRef
56. Zhang Y, Liu X, Cui Z, Yang X, Yeung KWK, Chu PK, Wu S. Synergistic effect of Ag-ZnO-HA nanocomposite laser cladding on Ti6Al4V implant against drug-resistant bacteria and cytotoxicity. ACS Appl Mater Interfaces. 2016;8(50):34335–34347. doi:10.1021/acsami.6b12376
    CrossRef
57. Hu X, Neoh KG, Zhang J, Kang ET, Wang W. Immobilization strategy for optimizing VEGF’s concurrent bioactivity towards endothelial cells and osteoblasts on implant surfaces. Biomaterials. 2012;33(32):8082–8093. doi:10.1016/j.biomaterials.2012.07.057
    CrossRef
58. Liu CX, Zhang DR, He Y, Zhao XS, Bai R. Modification of membrane surface for anti-biofouling performance: effect of anti-adhesion and anti-bacteria approaches. J Membr Sci. 2010;346(1):121–130. doi:10.1016/j.memsci.2009.09.028
    CrossRef
59. Liu Y, Zhao Q. Influence of surface energy of modified surfaces on bacterial adhesion. Biophys Chem. 2005;117(1):39–45. doi:10.1016/j.bpc.2005.04.015
    CrossRef
60. Gao G, Lange D, Hilpert K, et al. The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides. Biomaterials. 2011;32(16):3899–3909. doi:10.1016/j.biomaterials.2011.02.013
    CrossRef
61. Gittens RA, Scheideler L, Rupp F, Hyzy SL, Geis-Gerstorfer J, Schwartz Z, Boyan BD. A review on the wettability of dental implant surfaces II: biological and clinical aspects. Acta Biomater. 2014;10(7):2907–2918. doi:10.1016/j.actbio.2014.03.032
    CrossRef
62. Doyle RJ. Contribution of the hydrophobic effect to microbial infection. Microbes Infect. 2000;2(4):391–400. doi:10.1016/S1286-4579(00)00328-2
    CrossRef
63. Gilbert P, Allison DG, McBain AJ. Biofilm community interactions: chance or necessity? BioLine Cardiff. 2001:11–22. https://hdl.handle.net/1822/6706
64. Hanaor DAH, Sorrell CC. Review of the anatase to rutile phase transformation. J Mater Sci. 2011;46(4):855–874. doi:10.1007/s10853-010-5113-0
    CrossRef
65. Joo HC, Lim YJ, Kim MJ, Kwon HB, Han JH. Characterization of titanium surfaces and its effect on photocatalytic bactericidal activity. Appl Surf Sci. 2010;257(3):741–746. doi:10.1016/j.apsusc.2010.07.054
    CrossRef
66. Cargnello M, Gordon TR, Murray CB. Solution-phase synthesis of titanium dioxide nanoparticles and nanocrystals. Chem Rev. 2014;114(19):9319–9345. doi:10.1021/cr500170p
    CrossRef

Abbreviations List

TiO? Titanium dioxide

AMPs Antimicrobial peptides

CHX Chlorhexidine

UV Ultraviolet

ROS Reactive oxygen species

AgNPs Silver nanoparticles

Appendix A. Prisma Flowchart.

Figure 1: PRISMA flowchart Click here to view Figure