Nano-Modified Titanium Implant Surfaces for the Prevention and Treatment of Peri-Implantitis: A Review

Introduction

Dental implants are regarded as one of the primary restorative options for partial or complete edentulism. Despite their high survival and success rates, peri-implantitis remains one of the most significant threats to long-term implant success. In the absence of effective intervention, the inflammatory process can progressively destroy peri-implant bone tissue, ultimately leading to implant failure. Studies have reported that the prevalence of peri-implantitis reaches 25.0% at the patient level and 18.0% at the implant level.¹ The clinical management of peri-implantitis aims to eliminate plaque biofilms and modify the implant surface and local microenvironment to achieve re-osseointegration.² Implant materials have undergone more than half a century of development, with titanium, titanium alloys, and zirconia currently being the most commonly used materials. Among these, titanium has become the preferred implant material due to its excellent biocompatibility, mechanical properties, and corrosion resistance.³ However, these materials inherently lack antibacterial activity, and their surface oxide layers are susceptible to passivation by bacterial lipopolysaccharides, thereby creating a microenvironment favorable for bacterial–host “secondary colonization”.⁴ To prevent and control the occurrence and progression of peri-implantitis, current research has focused on enhancing the antibacterial properties of implants through various approaches, including the development of novel biomaterials and surface modification strategies.⁵

Accurate radiographic assessment is a prerequisite for effective treatment. The diagnosis of peri-implantitis relies not only on clinical parameters such as probing depth and bleeding scores, but also on radiographic evidence to determine the extent and morphology of marginal bone loss.² Intraoral periapical radiography, characterized by its ease of use, low radiation dose, and high spatial resolution (approximately 10–18 lp/mm), remains the standard modality for radiographic assessment. Although panoramic radiography involves a higher radiation dose (approximately 5–10 times that of periapical radiography) and is subject to tomographic distortion, it still offers complementary value in cases where intraoral imaging is challenging or when a broad assessment of multiple implants is required. Cone beam computed tomography (CBCT), as a three-dimensional imaging technique, eliminates the structural overlap and distortion inherent in two-dimensional images. However, artifacts induced by titanium and zirconia implants can substantially compromise image quality, and its effective radiation dose (approximately 50–100 μSv) is considerably higher than that of periapical radiography. Therefore, CBCT is not recommended for routine follow-up and should be reserved for specific indications such as complex bone defects, suspected neurovascular injury, or preoperative planning for secondary interventions.⁶ The ex vivo study by Tzortzakis NG et al further confirmed that, although CBCT demonstrated higher sensitivity in detecting peri-implant bone defects (95%) compared with periapical radiography (80.5%), no statistically significant difference was observed in observer detectability between the two modalities.⁷ This finding supports the role of CBCT as a complementary tool rather than a routine alternative. Thus, the choice of imaging modality must balance diagnostic efficacy, radiation exposure, and clinical needs, with a systematic interpretation protocol serving as the cornerstone of accurate diagnosis and treatment planning.

Building upon such diagnostic precision, the challenge now shifts to therapeutic intervention: how to achieve long-term antibacterial reconstruction and bone re-integration on the implant surface after a definitive diagnosis remains a core challenge in current clinical practice. The convergence of nanomedicine and biomaterials science has opened new avenues for the prevention and treatment of peri-implantitis. Traditional methods, such as mechanical debridement, flap surgery, and guided bone regeneration (GBR), can temporarily remove plaque but fail to prevent the recurrent formation of biofilms.² By developing nanomodified implants with intrinsic antibacterial activity, it is possible to achieve broad-spectrum, long-lasting, and biosafe plaque inhibition without reliance on antibiotics. Implant surface nano-modification involves functionalization at the atomic level, enabling precise regulation of surface topography, composition, and chemical properties within the 1–100 nm scale.⁸ Such strategies can exert antibacterial effects through direct or indirect mechanisms. Direct strategies employ nanostructures with specific morphologies (eg., nanopillars) or functional nanomaterials (eg., metallic, carbon-based, and polymeric nanomaterials). Indirect strategies involve nano-based drug delivery systems, which enhance antibacterial agent penetration into biofilms, enable controlled drug release, and improve stability in the complex oral physiological environment.^9–11 For example, Sanhueza C et al successfully constructed antibacterial membranes composed of poly-3-hydroxybutyrate and silver nanoparticles (AgNPs) on implant surfaces using electrospinning technology. In vitro studies demonstrated that these composite membranes exhibited significant planktonic bacterial inhibition and biofilm eradication capacity against peri-implantitis-related pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus mutans; their inhibitory effect against Candida albicans was dependent on the loading concentration of AgNPs.¹²

Within the complex oral microbial ecosystem, the antibacterial efficacy of nano-modified implant surfaces arises not from a single mechanism but from the synergistic action of multiple physical and chemical pathways, including physical disruption, ion release, reactive oxygen species (ROS) generation, and photothermal conversion (ie., light-to-heat conversion). This multi-mechanistic synergy significantly enhances the clearance efficiency of biofilms and drug-resistant bacteria.¹³ More importantly, nanomodified implants can achieve localized, targeted, and sustained antibacterial effects, selectively eliminating pathogenic bacteria while minimizing adverse impacts on host tissues and the peri-implant microecological environment (ie., the complex microbial and host ecosystem surrounding the implant). These advantages provide strong clinical translation potential for overcoming current limitations in the prevention and treatment of peri-implantitis.^14,15 Despite these advances, the clinical translation of nano-modified implant surfaces still faces multiple barriers. These include insufficient long-term coating stability, uncontrolled in vivo degradation, potential cytotoxicity, and complex regulatory approval pathways. Such bottlenecks significantly delay the translation of promising technologies from bench to bedside.

Existing reviews have laid an important foundation for mechanistic research and application development of implant surface nano-modification. However, most studies focus on individual functional mechanisms or general application scenarios, lacking multi-strategy synergistic analyses and systematic evaluations of clinical translation potential specifically targeting peri-implantitis.^16,17 Accordingly, this review proposes the following hypothesis: integrating nanotopography modulation, nanomaterial functionalization, and nano-drug delivery systems can construct a synergistic antibacterial and osteogenic interface on implant surfaces, thereby effectively preventing and treating peri-implantitis. Therefore, this review integrates current research progress and future trends in implant surface nano-modification strategies and establishes a comprehensive framework that combines mechanistic insights with clinical relevance. First, the complex characteristics of peri-implantitis-associated microbial ecology and the limitations of traditional antibacterial strategies are reviewed in detail. Subsequently, the antibacterial advantages of nanomodified surfaces achieved through the synergy of multiple physical and chemical mechanisms are analyzed. Based on this analysis, existing nano-modification strategies are classified into three major categories for in-depth discussion: (1) nanotopography modulation, (2) nanomaterial functionalization, and (3) construction of nano-drug delivery systems. Finally, the design principles of nano-modified implant coatings are comprehensively discussed, and key challenges and future research directions for clinical translation are prospectively addressed.

Antibacterial Requirements and Challenges in Peri-Implantitis

Complexity of the Peri-Implant Microbiota

The oral cavity, characterized by a warm, moist, and nutrient-rich environment, provides an ideal habitat for the growth and proliferation of bacteria, fungi, and viruses. Data from the Human Microbiome Project (HMP) indicate that the oral microbiota comprises more than 700 distinct species.¹⁸ The complex biofilms formed by these microorganisms play a crucial role in maintaining both oral and systemic health. Under physiological conditions, the oral microbiota interacts with the host in a harmonious and symbiotic manner. However, disruption of this microbial homeostasis allows pathogenic bacteria to proliferate uncontrollably, leading to significant alterations in microbial composition that subsequently trigger and exacerbate inflammation and tissue damage.¹⁹

Studies have demonstrated that, in a healthy state, the composition of peri-implant microbiota differs significantly from that of the natural periodontal microbiota, although certain similarities exist and both maintain a relatively stable ecological balance.²⁰ Healthy peri-implant tissues are predominantly colonized by Firmicutes and Proteobacteria, with Streptococcus and Neisseria being particularly abundant and accounting for more than 40% of the total microbiota. In contrast, subgingival plaque from patients with peri-implantitis exhibits a higher bacterial load, increased species diversity, and a more complex microbial composition compared with that from healthy implants. Members of the red complex, including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, are significantly more abundant in peri-implantitis than in healthy peri-implant sites.^21,22 Although the microbial profiles of peri-implantitis and periodontitis are both dominated by pathogenic bacteria such as Porphyromonas gingivalis and Tannerella forsythia, the proportion of pathogenic species is higher in peri-implantitis, whereas the microbiota associated with periodontitis is more diverse and complex.²³ Approximately 22 high-abundance pathogenic bacterial species have been identified in peri-implantitis, 21 of which are also commonly detected in periodontitis. However, certain bacterial species frequently observed in periodontitis, including nucleatum subsp. vincentii, A. cardiffensis, Olsenella spp., Selenomonas sputigena,and Corynebacterium matruchotii, are rarely detected in peri-implantitis.²⁴

In recent years, Fernandes GVO et al have significantly updated Socransky’s classical complex theory by proposing the GF-MoR (Gram-positive Enriched–Microbial Dysbiosis/Antibiotic Resistance) complex model for periodontal and peri-implant diseases. The GF-MoR complex reveals more intricate patterns of microbial interaction within the peri-implant microecology: beyond the classical red complex pathogens, certain previously overlooked microorganisms—such as species of Selenomonas, Synergistetes, and Bacteroidetes—play key roles in the dysbiosis associated with peri-implantitis. This updated model emphasizes that it is the overall structural and functional shift of the microbial community (ie., dysbiosis), rather than the mere presence of specific pathogens, that constitutes the core mechanism driving the initiation and progression of peri-implantitis.²⁵

Treatment Strategies for Peri-Implantitis and Their Limitations

Natural teeth are anchored to the alveolar bone by the periodontal ligament, whereas dental implants are directly integrated with bone through osseointegration. This structural difference renders peri-implant tissues more susceptible to bacterial insult: once biofilm is formed and matures on the implant surface, the inflammatory response is more intense and tissue destruction more rapid.²⁰ Contemporary management of peri-implantitis follows the principle of “diagnosis first, graded intervention,” with the core objectives of controlling infection, halting bone loss, and achieving re-osseointegration whenever possible.^2,20 Current clinical treatment protocols are largely structured around the Cumulative Interceptive Supportive Therapy (CIST) protocol, encompassing plaque control, antimicrobial therapy, antibiotic administration, and resective/regenerative surgery—or the stepwise care pathway recommended by the EFP S3 Level Clinical Practice Guideline (non-surgical debridement → reassessment → surgical intervention → supportive care).²⁶ Although these modalities may improve clinical parameters in the short term, their long-term efficacy remains uncertain, they are heavily technique-sensitive, and they are inherently limited in their capacity to reverse established bone-implant interface compromise. The specific limitations of each approach are detailed below.

Non-surgical therapy, primarily centered on mechanical debridement and supplemented by air polishing, laser therapy, or photodynamic therapy, aims to remove plaque biofilms from the implant surface. However, the complex threaded topography and rough surface characteristics of dental implants preclude complete biofilm elimination. Conventional instruments cannot effectively access the deep implant-bone interface, and residual biofilms readily recolonize within weeks, leading to recurrent inflammation,^27,28 Current evidence indicates that adjunctive modalities such as laser or photodynamic therapy fail to significantly enhance long-term clinical outcomes and carry inherent procedural risks, including soft tissue emphysema and thermal injury.^29,30

Antibiotic therapy, administered either systemically or locally, is frequently employed as an adjunct to mechanical debridement to suppress residual pathogens.³¹ However, antibiotics are incapable of penetrating or eradicating mature biofilm structures, and their bacteriostatic effects do not translate into sustained clinical stability.³² Furthermore, conventional antibiotic regimens lack microbial specificity and cannot discriminate between pathogenic and commensal bacteria. Prolonged or repeated antibiotic exposure disrupts oral microecological homeostasis, not only compromising long-term therapeutic efficacy but also engendering serious health risks, including the selection of drug-resistant strains, dysbiosis, and secondary infections.^33,34

Surgical therapeutic strategies for peri-implantitis are categorized into resective and surgical bone regenerative procedures, or a combination of both.³⁵ Resective surgery, including implantoplasty and flap debridement, aims to smooth rough surfaces and eliminate peri-implant pockets to create a cleansable anatomical environment.³⁶ However, this approach comes at the expense of sacrificing bone and/or soft tissue, may compromise implant mechanical integrity, and carries the risk of aesthetic gingival recession. Its outcomes are highly operator-dependent, and it cannot restore lost bone-implant contact.³⁷ Surgical bone regenerative procedures employ bone substitutes, barrier membranes, and bioactive agents to promote the reconstruction of peri-implant bone defects.³⁸ Nevertheless, regenerative outcomes are highly contingent on defect morphology (eg., three-wall intrabony defects) and are associated with complications such as membrane exposure, infection, and graft displacement.^39,40 Current evidence is insufficient to confirm predictable, complete re-osseointegration, and long-term stability remains controversial.⁴¹ In recent years, mechanical surface refinement technologies have emerged as a novel approach to surgical debridement. The iMPACT implant planer, used in conjunction with the Quadrant protocol, enables standardized intraoral implantoplasty, efficiently removing contaminants and implant threads from exposed implant surfaces to generate a smooth surface finish. In vitro validation has confirmed significantly reduced plaque adhesion on treated surfaces, and clinical case reports have demonstrated stable medium- to long-term outcomes postoperatively.⁴²

Supportive maintenance therapy constitutes an indispensable component of post-treatment care for peri-implantitis, requiring regular (every 3–6 months) professional debridement and reassessment to sustain therapeutic gains and prevent disease recurrence.² However, long-term patient compliance remains generally poor, and the economic and time burdens associated with supportive peri-implant care substantially exceed those of periodontal maintenance in natural dentition. Evidence indicates that irregular maintenance is associated with a 3- to 4-fold increased risk of peri-implantitis recurrence.^43,44

In summary, although existing therapeutic modalities can, to varying degrees, “control” the progression of peri-implantitis, they share a common fundamental limitation: the inability to construct an active, durable, and microenvironment-adaptive antibacterial and osteogenic functional interface on the implant surface.

Antibacterial Advantages of Implant Surface Nano-Modification

Implant surface nano-modification strategies, through the construction of biologically active nanostructures or functional coatings, provide innovative solutions for the prevention and treatment of peri-implant infections. By enabling multi-mechanistic antibacterial and anti–drug-resistant effects, targeted action to minimize side effects, effective biofilm penetration for infection eradication, compatibility with osseointegration promotion, and long-term efficacy to prevent recurrence, implant surface nano-modification effectively addresses the “four major contradictions” inherent in traditional antibacterial approaches: (1) the conflict between antimicrobial efficacy and drug resistance; (2) the conflict between localized antibacterial activity and systemic safety; (3) the conflict between antibacterial performance and osseointegration; and (4) the conflict between short-term effectiveness and long-term stability. These advantages collectively underpin the emergence of nano-modification as a core research direction in the prevention and treatment of peri-implantitis.

First, nanomodified surfaces provide novel bactericidal strategies for peri-implantitis treatment through diverse antibacterial mechanisms. Unlike conventional antibiotics, which exert their effects by targeting specific biochemical pathways, the antibacterial activity of nanomodified surfaces primarily arises from their intrinsic physical structures and chemical reactivity. These surfaces can directly disrupt bacterial cell integrity and function through multiple pathways, thereby achieving efficient bacterial eradication and demonstrating particular advantages against drug-resistant bacteria and biofilms.¹³ Broadly, the antibacterial mechanisms of nanomodified surfaces can be categorized into physical, chemical, and physicochemical synergistic mechanisms. Importantly, these mechanisms do not operate independently or in a simple additive manner; instead, high-efficiency antibacterial effects are achieved through the synergistic integration of multiple pathways.

Physicomechanical mechanisms primarily rely on the topographical features of nanomaterials themselves. For instance, black silicon nanopillars or graphene oxide nanosheets utilize their sharp nanoscale protrusions to physically pierce bacterial cell membranes like “nano-daggers,” leading to cytoplasmic leakage and bacterial death.^45,46 The advantage of such mechanisms lies in their physical mode of action, which is less prone to inducing bacterial resistance and exhibits broad-spectrum bactericidal activity against various bacterial species. Photothermal conversion represents another important physical antibacterial strategy. Gold nanoparticles or black phosphorus nanosheets possess unique photothermal properties, enabling them to convert light energy into heat upon near-infrared irradiation. This localized hyperthermia effect can rapidly eliminate bacteria and is particularly suitable for controlling localized infections.⁴⁷ Recent studies have further demonstrated that gold nanostar-coated titanium implants produce significant antibacterial effects under near-infrared irradiation while simultaneously promoting osteogenic differentiation.⁴⁸ Black phosphorus nanosheets, owing to their excellent photothermal performance and biodegradability, show promising potential in the treatment of peri-implantitis.⁴⁹

Chemical mechanisms involve the release of chemical substances or the catalysis of chemical reactions by nanomaterials. Silver nanoparticles are a typical representative of this mechanism, with their advantage lying in a “multi-target” attack mode. The released silver ions first bind to bacterial cell membranes, disrupting their integrity; subsequently, they enter bacterial cells and bind to thiol groups in enzymes, inactivating them and interfering with respiration and metabolism. Silver ions can also intercalate into DNA double strands, hindering bacterial replication, while simultaneously inducing the generation of abundant reactive oxygen species, causing oxidative damage.⁵⁰ This multi-target synergistic action endows silver nanoparticles with exceptionally high antibacterial efficacy, making it difficult for bacteria to develop resistance through single mutations.

Physicochemical synergistic mechanisms represent the core design concept of nano-modified surface strategies. Han et al recently reported a multifunctional nanoplatform based on silver nanoparticle-graphene oxide composites. This platform achieves efficient treatment of peri-implantitis through precisely regulating the spatiotemporal distribution of reactive oxygen species. Its unique advantages stem from multiple synergistic mechanisms: graphene oxide nanosheets not only exert physical bactericidal effects through their sharp edges but also serve as carriers to enhance the stability and local enrichment of silver nanoparticles; the loaded silver nanoparticles achieve chemical bactericidal functions through sustained release of silver ions. More critically, this platform enables spatiotemporally controlled release of reactive oxygen species—rapidly releasing high concentrations at the initial infection stage to eliminate planktonic bacteria and mature biofilms, followed by maintaining low levels to promote osteoblast differentiation and bone tissue regeneration. This “first sterilization, then repair” programmed regulation mode enables the composite to significantly promote peri-implant bone regeneration while eradicating mature biofilms.⁵¹ Table 1 summarizes the principal antibacterial mechanisms of nanomodified surfaces and representative nanomaterials.

Table 1 Antibacterial Mechanisms of Nano-Modified Surfaces and Representative Nanomaterials

Second, nano-modified implant surfaces can precisely target the implant–bacteria interface, thereby reducing systemic side effects and significantly improving treatment safety. Through mechanisms such as microenvironment responsiveness and charge-mediated targeting, nanomodified implant surfaces can selectively release antibacterial components at infected sites while minimizing damage to surrounding healthy tissues.^61,62 For example, silver-loaded nano-coatings enable the sustained release of low concentrations of silver ions at the implant surface, effectively inhibiting the colonization of pathogenic microorganisms without inducing significant cytotoxicity to host cells or distant organs.^10,63 Similarly, pH-responsive nanoparticles remain dispersed and stable in healthy tissues but aggregate within the acidic microenvironment of infected peri-implant sites, thereby achieving high local bactericidal concentrations while sparing adjacent normal tissues.⁶⁴

In addition, nanomodified implant surfaces exhibit strong antibacterial activity, with particularly notable efficacy in penetrating and eradicating persistent biofilms.⁶⁵ For instance, small-sized ionic nanoparticles can penetrate the extracellular polymeric substance (EPS) matrix and release antibacterial agents under acidic conditions.⁶⁶ Moreover, electrostatic interactions between cationic nanoparticles and negatively charged bacterial membranes enhance their penetration and retention within biofilms.⁶⁷ Furthermore, titanium dioxide nanotube arrays modified with platinum nanoparticles can generate both antibacterial ROS and localized hyperthermia under visible or ultraviolet light stimulation, enabling combined physicochemical elimination of persistent bacteria within biofilms and effectively addressing recurrent biofilm-associated infections.⁶⁸

Meanwhile, nano-modification strategies confer implants with the capacity to synergistically regulate the dual biological functions of antibacterial activity and osteogenesis promotion.⁶⁹ This capability is primarily achieved through precise control of surface nanotopography, modulation of chemical composition, and incorporation of bioactive factors (eg., Sr²⁺, Mg²⁺, BMP-2) 49.⁷⁰ For example, anodized titanium implants can form ordered TiO₂ nanotube arrays (TNTs) on their surfaces. These structures not only reduce initial bacterial adhesion through physical effects but also promote the adhesion, proliferation, and differentiation of gingival fibroblasts and osteoblasts, thereby creating a favorable biological environment for osseointegration while simultaneously preventing infection.⁷¹ In addition, nano-hydroxyapatite (HA) coatings have attracted considerable attention due to their compositional similarity to natural bone mineral. Nanohydroxyapatite/Polyamide 66 (n-HA/PA66) bone tissue scaffolds fabricated using 3D printing technology exhibit excellent biosafety and biocompatibility, effectively induce new bone formation, and further accelerate and optimize osseointegration under appropriate functional loading conditions.⁷²

Finally, nano-modified surfaces incorporating programmed drug loading and sustained-release capabilities enable long-term and stable antibacterial activity at the implant interface. The core principle involves utilizing nanostructures as “drug reservoirs” to efficiently load antibacterial agents, including antibiotics and metal ions, onto implant surfaces.^17,73,74 By precisely controlling nanostructure size, morphology, and surface chemistry, drug release kinetics can be finely tuned, thereby effectively overcoming the rapid drug depletion and therapeutic failure associated with the burst release characteristic of conventional coatings.⁷⁵ Such systems can maintain local antibacterial concentrations within an effective therapeutic window during the critical postoperative period—from several hours to several weeks—thereby covering the peak risk of acute postoperative infection while also providing medium- to long-term protection against recurrent peri-implant infections.⁷⁶

Application of Nano-Modification in the Management of Peri-Implantitis

Implant surface nano-modification confers antibacterial properties to implants through three principal strategies: (1) surface nanotopography modulation, which utilizes nanopillars, nanotubes, or nanopores to achieve physical bactericidal effects while promoting integration with surrounding soft tissues; (2) surface nano-component functionalization, which incorporates metallic nanomaterials, carbon-based nanomaterials, or nanopolymers to enable multi-mechanistic synergistic antibacterial activity; and (3) construction of nano-drug delivery systems, which allow controlled or stimuli-responsive release of antibacterial agents and can simultaneously load osteogenic bioactive factors to promote osseointegration. These three strategies may be applied independently or in combination, thereby establishing a multi-scale, multi-mechanism synergistic antibacterial defense system on the implant surface. Such systems significantly reduce the risk of postoperative infection and provide strong support for improving the long-term success rate of dental implants.

Nanotopography

Implant surface nanotopography modification can be achieved using various techniques, including anodization, electron beam lithography, and nanoimprint lithography. These methods enable the fabrication of nanoscale (1–100 nm) surface features, such as nanopillars, nanotubes, nanoneedles, and nanopores.^77–80 Studies have demonstrated that within this dimensional range, bacterial adhesion to implant surfaces is significantly reduced and biofilm formation is suppressed, thereby effectively decreasing the risk of implant-associated infection.⁵³

On the one hand, specific nanotopographical features on implant surfaces (eg., nanoneedles and nanopillars) can induce deformation and rupture of bacterial cell membranes through mechanical cutting or piercing effects, ultimately leading to bacterial death.⁸¹ For example, Hayles A et al fabricated nanopillar arrays mimicking dragonfly wings on titanium surfaces using acid etching techniques and demonstrated that these structures caused bacterial membrane stretching and rupture during bacterial movement (Figure 1A and B).⁸² Similarly, Chopra D et al reported that nanopillar arrays stretch bacterial membranes via adhesive forces, thereby enhancing antibacterial efficiency. Notably, structures with smaller tip diameters exhibit stronger bactericidal activity due to localized stress concentration.⁸³

Figure 1 Nanotopography-guided antibacterial effects. (A) Nanopillar arrays mimicking dragonfly wings. (B) Bactericidal mechanisms of nanotopographical surfaces. Reprinted from Materials Today Chemistry, 22, Hayles A, Hasan J, Bright R, et al, Hydrothermally etched titanium: a review on a promising mechano-bactericidal surface for implant applications, 100622, Copyright 2021, with permission from Elsevier82 (C) Representative SEM images of flat control, nanospike (NS), and nanonetwork (NN) surfaces, along with corresponding surface height and area measurements (table); scale bar: 2 µm. (D) Effect of nanotopographies on P. aeruginosa. Bacteria were incubated on flat, NS, or NN coated or uncoated surfaces for 24 h. (i) The samples were fixed and visualized by SEM to assess morphology; scale bar, 2 μm (top panel) and 600 nm (bottom); blue arrows indicate cell surface appendages. (ii) Live/dead staining indicates viable bacteria (green) or dead bacteria (red); scale bar, 50 μm. (iii) The levels of cell survival quantified using Fiji, normalized to uFlat represented as bars with individual values and standard deviation. Statistical significance between conditions was tested using Kruskal–Wallis test with a p-value <0.05 (*) considered significant, and <0.001 (**) highly significant. Metabolites were isolated from the (iv) biofilm and (v) planktonic bacteria, then submitted to triple quadrupole mass spectrometry to determine levels of QSM. Average expression is represented as a heatmap, where red-colored bars represent upregulation and blue downregulation compared to uFlat. Statistical significance between conditions was tested using a two-tailed unpaired homoscedastic t test with a p-value <0.05 (*) considered significant. These surfaces, particularly cNN, can inhibit bacteria biofilm formation and reduce QSM in P. aeruginosa. Reprinted from Cuahtecontzi Delint R, Ishak MI, Tsimbouri PMet al Nanotopography Influences Host-Pathogen Quorum Sensing and Facilitates Selection of Bioactive Metabolites in Mesenchymal Stromal Cells and Pseudomonas aeruginosa Co-Cultures. ACS Appl Mater Interfaces. 2024;16(33):43374–43386.84 (E) Schematic illustrating the structure-dependent antibacterial mechanism of nanotopography, the efficacy of which is regulated by parameters such as feature height and spacing. Reprinted from Butler J, Handy RD, Upton M, Besinis A. Review of Antimicrobial Nanocoatings in Medicine and Dentistry: Mechanisms of Action, Biocompatibility Performance, Safety, and Benefits Compared to Antibiotics. ACS Nano. 2023;17(8):7064–7092.85

On the other hand, high-density, high–aspect ratio nanotopographies can also restrict biofilm spreading and maturation on implant surfaces. Studies have shown that nanoscale surface features reduce the number of available bacterial binding sites, thereby inhibiting initial bacterial adhesion.⁸⁶ For instance, Cuahtecontzi Delint R et al developed nanotopographical coatings with nanospikes (NS) and nanonetworks (NN) on titanium discs, which significantly reduced Pseudomonas aeruginosa biofilm formation and downregulated bacterial virulence factor expression (Figure 1C and D).⁸⁴ Kunrath MF et al further demonstrated that, compared with micro-textured surfaces, nano-textured titanium surfaces exhibited slightly enhanced antibacterial properties.⁸⁷ Importantly, the antibacterial efficacy of nanotopography is closely associated with structural parameters such as height, diameter, and spacing. Nanospikes or nanopillars must possess appropriate dimensions to physically interact with bacterial cell membranes (Figure 1E).⁸⁵ Ivanova EP et al reported that nanopillars with a height of 360 nm exhibited superior bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus compared with nanopillars measuring 220 nm or 420 nm, as they more effectively stored and released mechanical energy through optimal elastic deformation.⁴⁵

In addition to their antibacterial properties, nanotopographical modifications significantly influence the integration of implants with surrounding soft tissues. Ordered nanotopographical surfaces promote the adhesion of fibroblasts and epithelial cells and enhance connective tissue formation, thereby establishing an effective soft tissue seal that serves as a biological barrier against bacterial invasion.^88,89 Moreover, nanotube arrays have been shown to regulate macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, thereby coordinating osteogenic and osteoclastic activities, promoting osseointegration, and reducing the risk of peri-implantitis.⁹⁰

In summary, implant surface nanotopography modification demonstrates considerable potential in inhibiting bacterial colonization and enhancing soft tissue integration, which may ultimately improve the long-term success of dental implants. However, most current evidence is derived from in vitro studies, and the clinical applicability of these approaches requires further validation through animal models and randomized controlled clinical trials.

Nanomaterials

The nano-modification of implant surfaces with metallic nanomaterials, carbon-based nanomaterials, and nanopolymers offers an alternative strategy to prevent post-implantation bacterial infections. A variety of such nanomaterials have been utilized for Ti surface modification, as summarized in Figure 2, and will be discussed in the following sections.

Figure 2 Functional nanomaterials engineered for implant surface Modification.

Metallic Nanomaterials

Metallic nanoparticles (MNPs), including silver, copper, zinc, and their corresponding oxide nanoparticles, have attracted substantial attention and have been widely investigated for antibacterial coatings due to their unique physicochemical properties, such as high specific surface area and enhanced interactions with bacterial membranes.⁹¹ Metallic nanoparticles exert antibacterial effects through multiple synergistic mechanisms, including physical membrane penetration, sustained metal ion release, induction of oxidative stress, and inhibition of essential enzymatic activities. Accordingly, surface modification of implants with metallic and metal oxide nanoparticles represents a feasible strategy for preventing post-implantation bacterial infections.

Silver nanoparticles (AgNPs) exhibit particularly strong antibacterial activity owing to their exceptionally high specific surface area and excellent ion release capacity. Their antibacterial mechanisms include: (1) attachment to microbial cell surfaces, leading to membrane damage and altered transport activity; (2) penetration into microbial cells, where they interact with intracellular organelles and biomolecules, thereby disrupting cellular functions; (3) induction of intracellular ROS generation, resulting in oxidative damage; and (4) modulation of cellular signaling pathways, ultimately leading to bacterial cell death (Figure 3A).⁵⁰ AgNPs synthesized via both biological and chemical methods demonstrate broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria (Figure 3B).⁹² Yuan Z et al immobilized AgNPs onto titanium implant surfaces using a chemical anchoring approach and reported antibacterial rates of 64.6% against Staphylococcus aureus and Escherichia coli, with significant inhibition of biofilm formation.⁹³ El-Telbany M et al evaluated the antibacterial and antibiofilm efficacy of AgNPs against Pseudomonas aeruginosa isolates obtained from patients with peri-implantitis and demonstrated that AgNPs exhibited strong antibacterial and antibiofilm activities across all tested concentrations (Figure 3C).⁹⁴ Importantly, differences in surface charge and the number of active sites mean that the size and shape of AgNPs are critical determinants of antibacterial performance.⁹² Smaller AgNPs, particularly those with diameters below 10 nm, possess larger specific surface areas and exhibit enhanced bactericidal effects. In terms of morphology, plate-like or triangular AgNPs with high-energy crystal facets generally display superior antibacterial activity compared with spherical, rod-shaped, or cubic counterparts.⁹⁵ However, the cytotoxicity of silver nanoparticles remains a core challenge for their clinical translation. Ahamed M et al indicated that the toxic effects of silver nanoparticles are closely related to their physicochemical properties, including particle size, morphology, surface charge, coating materials, and release kinetics. For instance, small-sized silver nanoparticles (<10 nm) are more prone to cellular internalization, inducing mitochondrial dysfunction and DNA damage.⁹⁶ Therefore, a precise balance between antibacterial efficacy and biosafety is essential for the clinical application of silver nanoparticles. This balance can be achieved through the following strategies: (1) optimizing particle size distribution by selecting dimensions within the 10–20 nm range that offer high antibacterial activity with relatively low cytotoxicity; (2) performing surface functionalization, such as coating with biocompatible polymers like polyethylene glycol or chitosan, to reduce non-specific cellular uptake; (3) controlling release kinetics via nanocarriers to achieve sustained low-dose release of silver ions, thereby avoiding excessively high local concentrations; and (4) establishing standardized toxicity evaluation systems that comprehensively assess cytotoxicity, genotoxicity, immunotoxicity, and long-term in vivo safety.⁹⁷

Figure 3 AgNPs-mediated antibacterial mechanisms. (A) The four most prominent routes of antimicrobial action of AgNPs. Reprinted from Dakal TC, Kumar A, Majumdar RS, Yadav V. Mechanistic Basis of Antimicrobial Actions of Silver Nanoparticles. Front Microbiol. 2016;7:1831.50 (B) TEM micrograph for silver nanoparticles showed the presence of spherical nanoparticles with the average size of 22 nm. Environ Chem Lett, Shende S, Gade A, Rai M. Large-scale synthesis and antibacterial activity of fungal-derived silver nanoparticles, 3, Copyright 2017, reproduced with permission from SNCSC.92 (C) AgNPs mediated reduction of P. aeruginosa biofilms. AgNPs showed increasingly reduction of P. aeruginosa biofilms. Treatment of bacterial biofilms with AgNPs revealed the efficacy of AgNPS in eradication of their biofilm, and the results were shown by estimation of OD measurements. Reprinted from El-Telbany M, El-Sharaki A. Antibacterial and anti-biofilm activity of silver nanoparticles on multi-drug resistance Pseudomonas aeruginosa isolated from dental-implant. J Oral Biol Craniofac Res. 2022;12(1):199–203.94

Similarly, copper nanoparticles (CuNPs) are widely investigated as candidate materials for antibacterial modification of implant surfaces. Rosenbaum J et al deposited CuNPs with an average diameter of 20 nm onto TiO₂ substrates using pulsed electrodeposition. The resulting CuNPs-coated surfaces exhibited high antibacterial efficacy against Staphylococcus aureus and Escherichia coli and significantly reduced bacterial adhesion.⁹⁸ Astasov-Frauenhoffer M et al fabricated CuNPs-coated titanium discs with varying copper concentrations via anodization and evaluated their antibacterial performance against Porphyromonas gingivalis. Their results demonstrated that antibacterial efficacy was closely associated with copper content, with surfaces containing 7–9 µg of copper significantly reducing the survival rate of Porphyromonas gingivalis.⁹⁹ Although CuNPs exhibit strong antibacterial activity, their relatively high cytotoxicity limits direct clinical application.¹⁰⁰ Consequently, additional biosafety evaluations are required to ensure effective antibacterial protection within a biocompatible concentration range. In addition, other metal oxide nanoparticles, such as ZnO, TiO₂, and CuO, also exert antibacterial effects through mechanisms including photocatalytic ROS generation and metal ion release.¹⁰¹ For example, Luo Q et al successfully fabricated a ZnO@ZnS nanorod array coating on implant surfaces using a hydrothermal method. This coating enabled controlled zinc ion release, exhibited strong antibacterial activity against Staphylococcus aureus and Escherichia coli, and promoted the adhesion and migration of human gingival fibroblasts, thereby enhancing soft tissue sealing and reducing the risk of peri-implantitis.¹⁰²

Carbon-Based Nanomaterials (CBNMs)

Carbon-based nanomaterials, primarily carbon nanotubes (CNTs) and graphene/graphene oxide (G/GO), exhibit notable antibacterial properties due to their highly ordered structural organization.¹⁰³ As a result, they have attracted considerable attention for use in antibacterial coatings on implant surfaces.

CNTs consist of graphene sheets rolled into tubular structures and can be classified into single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) based on the number of graphene layers.¹⁰⁴ Studies have demonstrated that CNTs can physically penetrate bacterial cell membranes, leading to membrane disruption and bacterial death, and thus exhibit bactericidal activity against both Gram-positive and Gram-negative bacteria.¹⁰⁵ Linklater DP et al reported that vertically aligned carbon nanotubes (VACNTs), characterized by an ultra-high aspect ratio and exceptional flexibility, can deform upon contact with bacteria and subsequently release stored elastic potential energy, resulting in strong bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus (Figure 4A and B).¹⁰⁶ In addition, Suo L et al showed that SWCNTs effectively inhibit early bacterial adhesion and biofilm maturation of Streptococcus mutans.¹⁰⁷ Notably, research conducted by the Hirschfeld J group highlighted the potential of CNTs as drug delivery platforms. Owing to their favorable biocompatibility, CNTs can serve as efficient drug carriers. By loading rifampicin and enabling sustained release, CNT-modified surfaces significantly reduced the biofilm-forming capacity of Staphylococcus aureus. Implant surfaces modified with MWCNTs demonstrated strong antibiofilm properties, offering a promising strategy for the prevention and treatment of peri-implantitis (Figure 4C and D).¹⁰⁸

Figure 4 (A) SEM images comparing the heights of high-aspect-ratio VACNTs: (i) 1 μm and (ii) 30 μm. False-color SEM images show (iii) S. aureus and (iv) P. aeruginosa attached to VACNT surfaces, demonstrating CNT bending and bacterial membrane deformation. All scale bars are 1 μm, unless otherwise indicated. (B) Bactericidal activity (i, iii) and attachment (ii, iv) of P. aeruginosa and S. aureus cells, respectively, on VACNT nanoarrays with different post-fabrication surface modifications. Statistical significance is denoted by ** (p < 0.05). Error bars represent ±1 standard deviation. Reprinted with permission from Linklater DP, De Volder M, Baulin VA et al High Aspect Ratio Nanostructures Kill Bacteria via Storage and Release of Mechanical Energy. ACS Nano. 2018;12(7):6657–6667, Copyright 2018, American Chemical Society.106 (C) Schematic diagram of anti-biofilm formation and pro-osteogenic differentiation on a CNT-modified titanium alloy surface. (D) Inhibition zones were determined by placing discs inverted onto agar plates in triplicate. Horizontal bars represent mean values ± SD. ***P ≤ 0.001. All data are presented as mean ± SD of three independent experiments. Reprinted from Nanomedicine, 13, Hirschfeld J, Akinoglu EM, Wirtz DC et al Long-term release of antibiotics by carbon nanotube-coated titanium alloy surfaces diminish biofilm formation by Staphylococcus epidermidis, 1587–1593, Copyright 2017, with permission from Elsevier108 (E) Antibacterial effect of GNP-coated i-disks on biofilm formation. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.001, ns = not significant. Reprinted from Pranno N, La Monaca G, Polimeni A et al Antibacterial Activity against Staphylococcus Aureus of Titanium Surfaces Coated with Graphene Nanoplatelets to Prevent Peri-Implant Diseases. An In-Vitro Pilot Study. International Journal of Environmental Research and Public Health. 2020;17(5):1568.109 (F) Antibacterial activity against P. gingivalis. The TNT-GO group showed a significant reduction in colony-forming units compared to the TNT and Ti groups (*p < 0.05, **p < 0.01), indicating superior antibacterial efficacy. Reprinted from Wu K, Cao X, Luo B et al Antibacterial effects and mechanisms of graphene oxide loaded on TiO2-nanotube-modified ti: an in vitro study. BMC Oral Health. 2025;25(1):1107.110

Both graphene oxide (GO) and reduced graphene oxide (rGO) possess antibacterial activity, which may be attributed to their inherent anti-adhesion properties against biofilms, mechanical membrane disruption, and ROS-mediated bactericidal mechanisms.¹¹¹ The antibacterial efficacy of GO and rGO depends on factors such as oxidation degree, particle size, concentration, and bacterial contact time.¹¹² For instance, Pranno N et al evaluated the antibacterial performance of titanium surfaces coated with graphene nanosheets using crystal violet staining assays. Their results demonstrated that graphene nanosheet modification significantly enhanced the antibacterial properties of titanium implants, representing an effective approach to improving implant antibacterial performance (Figure 4E).¹⁰⁹ Similarly, Wu K et al successfully fabricated a TNT-GO composite via anodization and electrodeposition. This composite exhibited significant antibacterial activity against Porphyromonas gingivalis and showed good biocompatibility without cytotoxic effects on human gingival fibroblasts; however, further in vivo studies are required to validate its antibacterial efficacy (Figure 4F).¹¹⁰ Moreover, the electrical conductivity of graphene and graphene oxide enables the immobilization of antibacterial agents such as AgNPs.¹¹³ Multiple studies have demonstrated that graphene–AgNP composites exhibit superior antibacterial activity compared with graphene or AgNPs alone.^114–117 This enhanced performance arises from synergistic effects, whereby graphene improves the stability and dispersion of AgNPs, while AgNPs amplify the antibacterial efficacy of graphene. Together, these composites effectively inhibit bacterial adhesion and proliferation, significantly reducing the risk of implant-associated infection.

Beyond their antibacterial efficacy, CBNMs can also enhance the mechanical properties and biological performance of implant surfaces and exhibit favorable osteogenic induction capability and biocompatibility.^118–121 Jang W et al demonstrated that rGO coatings exert dual biological functions by inhibiting Streptococcus mutans adhesion while promoting osteoblast proliferation and differentiation. Such materials not only help prevent peri-implantitis by reducing bacterial adhesion but also enhance osseointegration, thereby improving implant stability and long-term clinical success.¹²²

Nanopolymers

Nanopolymers exert antibacterial effects either through their intrinsic properties or by acting as nanocarriers that load and control the release of antibacterial agents, demonstrating promising potential for preventing implant-related infections. Commonly used polymers include chitosan (CS), polycaprolactone (PCL), and poly (lactic-co-glycolic acid) (PLGA), which can be fabricated into nanofibers, nanoparticles, or hydrogels.

Chitosan exhibits favorable antibacterial activity and biocompatibility, typically existing in the form of nanofibers or nanoparticles and often being combined with other nanomaterials. Its antibacterial activity primarily depends on its overa Pseudomonas aeruginosa and Staphylococcus aureusll cationic charge, which interacts with negatively charged bacterial membranes, disrupts membrane integrity, and ultimately leads to bacterial death.^123,124 However, chitosan generally requires surface modification to achieve improved adhesion to titanium substrates. For instance, Cheng YF et al deposited AgNPs onto catechol-containing chitosan coatings, effectively inhibiting bacterial adhesion on titanium implant surfaces. Experimental results demonstrated inhibited growth of both Staphylococcus aureus and Escherichia coli, with a more pronounced bacteriostatic effect against Staphylococcus aureus.¹²⁵ Notably, owing to its excellent gelling properties, chitosan can form uniform films on implant surfaces, while the abundant amino and hydroxyl groups along its molecular chains provide ideal sites for chemical modification. Through precise chelation of metal ions and incorporation of composite nanomaterials, chitosan-based systems can synergistically enhance antibacterial performance and mechanical properties.^126–128 For example, Mishra SK et al encapsulated polyvinyl alcohol (PVA)-capped AgNPs within a chitosan matrix coated on titanium implants, significantly improving the performance of the nanocomposite and reducing the generation of harmful by-products. In vitro studies showed that this composite not only exhibited improved functional characteristics but also enhanced bactericidal activity against Staphylococcus aureus and Escherichia coli.¹²⁹ Similarly, Palla-Rubio B et al combined the antibacterial properties of chitosan with the osteoinductive properties of silica to fabricate a sol–gel composite coating. In vitro analyses confirmed that this coating effectively released silica, improved bone formation efficiency, and enhanced antibacterial activity by 5–10% (Figure 5A).¹³⁰ In addition, chitosan-based composite materials have demonstrated broad application prospects in the field of guided bone regeneration. Chatzipetros E et al fabricated porous nano-hydroxyapatite/chitosan scaffolds and demonstrated their excellent bone regeneration capacity in a rat calvarial defect model. The synergistic effect between the antibacterial properties of chitosan and the osteoconductive properties of nano-hydroxyapatite enables this composite material to promote bone tissue regeneration while controlling infection.⁹⁷

Figure 5 Nanopolymer Modification Strategies for Implant Surfaces. (A) Schematic of a silica–chitosan hybrid material as an antibacterial coating for titanium implants. Reprinted from 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. Carbohydr Polym. 2019;203:331–341.130 (B) Schematic of nanoscale surfaces and sustained antibiotic release from polymeric coatings for implants with combined antibacterial and osseointegration-promoting functions. Reprinted from Kunrath MF, Rubensam G, Rodrigues FVF et al Nano-scaled surfaces and sustainable-antibiotic-release from polymeric coating for application on intra-osseous implants and trans-mucosal abutments. Colloids Surf B Biointerfaces. 2023;228:113,417.131

Polycaprolactone (PCL), as a biodegradable synthetic nanopolymer, has demonstrated significant application potential in the prevention and treatment of peri-implantitis. Its antibacterial function is primarily achieved through the construction of localized drug delivery systems, among which electrospun nanofibrous membranes are commonly used carriers.¹³² As a nanocarrier, the hydrophobic nature of PCL makes it particularly suitable for loading lipophilic drugs (eg., doxycycline and clindamycin), with drug release governed by the synergistic effects of diffusion and polymer degradation.¹³³ For example, Lan SF et al incorporated the antibacterial agent metronidazole into custom-designed PCL/alginate composite rings. Their results showed that drug release could be regulated by adjusting the PCL/alginate weight ratio to achieve the minimum inhibitory concentration required for effective antibacterial protection. The composite rings released approximately 50% of the drug within the first 48 h, followed by sustained release over the remaining study period, extending the release duration to more than 30 days and effectively avoiding the initial burst release commonly observed in traditional drug delivery systems.¹³⁴ To further enhance biological activity, PCL is often combined with inorganic antibacterial components to construct multifunctional coatings. Kim HW et al encapsulated tetracycline within a composite coating composed of hydroxyapatite (HA) and PCL. The resulting coating exhibited high porosity (approximately 87%) and controllable pore sizes (150–200 μm). This porous structure, characterized by a high specific surface area and favorable mass transport properties, is well suited for drug delivery applications while simultaneously enabling controlled antibiotic release and enhancing osteoconductivity and overall biological activity.¹³⁵ Similarly, poly(lactic-co-glycolic acid) (PLGA) can be fabricated into nanoparticles using emulsification–solvent evaporation techniques to encapsulate antibacterial agents. The degradation rate and drug release kinetics of PLGA can be precisely regulated by adjusting its molecular weight and lactic acid–to–glycolic acid (LA:GA) ratio, thereby maintaining long-term effective antibacterial concentrations at the infection site. This sustained delivery effectively disrupts bacterial biofilms and eliminates pathogenic bacteria (Figure 5B).¹³¹

In summary, nanopolymer systems represented by CS, PCL, and PLGA exhibit distinct advantages in the prevention and treatment of implant-associated infections due to their controllable drug release behavior and multifunctional modification potential. These materials not only enable long-term, controlled release of antibacterial agents but also synergistically enhance osseointegration through composite design. With ongoing advances in surface engineering, microenvironment-responsive mechanisms, and multi-factor synergistic delivery strategies, nanopolymer platforms are expected to overcome current limitations and facilitate their translation from basic research to clinical applications.

Nano-Drug Delivery System

Traditional antibacterial coatings on implant surfaces often exhibit a “burst release” phenomenon during the early stage after implantation, resulting in a rapid decline in local drug concentrations below the minimum inhibitory concentration. Consequently, these coatings fail to adequately cover the high-risk infection period of 2–4 weeks following surgery.² The use of nanotube or nanopore structures as reservoirs for antibacterial agents not only enables stable encapsulation of drug molecules but also allows precise regulation of drug release kinetics by adjusting structural parameters such as pore size and depth. For example, Zhao L et al anchored AgNPs onto the inner walls of titanium dioxide nanotubes and achieved precise control over the size and release behavior of silver nanoparticles by adjusting parameters such as AgNO₃ concentration and immersion time. In vivo experiments demonstrated that this silver-loaded nanotube system efficiently eliminated planktonic bacteria during the early postoperative period and continuously inhibited bacterial adhesion for up to 30 days, thereby blocking biofilm formation pathways and significantly reducing the risk of early- to mid-stage infections (Figure 6A).¹³⁶ In another study, Baghdan E et al constructed PLGA nanocoatings loaded with norfloxacin, whose release kinetics exhibited a typical biphasic profile: an initial burst release within 48 h, followed by sustained release at a constant rate until day 15. This coating reduced the number of viable Escherichia coli by 99.83% and demonstrated significant antibiofilm activity.¹³⁷

Figure 6 (A) (i) Non-cumulative silver ion release profiles from the NT-Ag system into PBS; (ii) Antibacterial rates against planktonic bacteria in the medium (Rp); (iii) Antibacterial rates against adherent bacteria on the specimen (Rₐ). Antibacterial assay data are expressed as means ± standard deviation (n = 3). Reprinted from Biomaterials, 32, Zhao L, Wang H, Huo K et al Antibacterial nano-structured titania coating incorporated with silver nanoparticles, 5706–5716, Copyright 2011, with permission from Elsevier.136 (B) Schematic illustration of the synthesis of VZZ-8 nanoparticles for bone-targeted, pH-responsive therapy of MRSA-induced prosthetic joint infection (PJI), and their in vitro antibacterial activity. Reprinted from J Control Release, 385, Liang S, Pan Y, Wang J et al Bone-targeting ZIF-8 based nanoparticles loaded with vancomycin for the treatment of MRSA-induced periprosthetic joint infection, 113965, Copyright 2025, with permission from Elsevier.138 (C) Synthesis of the ZnO-GO/CS/β-GP hydrogel and its antibacterial efficacy against Porphyromonas gingivalis. Groups: cg, control; a, CS/β-GP; b, 1% ZnO-GO/CS/β-GP; c, 3% ZnO-GO/CS/β-GP. *P < 0.05, **P < 0.01, *P < 0.001. Reprinted from Huang H, Han R, Huang PP et al Preparation and Performance Evaluation of a Zinc Oxide-Graphene Oxideloaded Chitosan-Based Thermosensitive Gel. J Microbiol Biotechnol. 2024;34(6):1229–1238.139

Nano-drug delivery systems, owing to their high specific surface area, can load various antibacterial agents (eg., antibiotics, metal ions, and antimicrobial peptides) and simultaneously activate multiple bactericidal pathways, including membrane disruption and ROS-mediated catalytic sterilization. This synergistic antibacterial strategy reduces the required dosage of individual drugs and lowers the risk of drug resistance.¹⁷ For instance, the Ma M team efficiently loaded the cationic antimicrobial peptide HHC-36 onto TiO₂ nanotube surfaces via vacuum-assisted adsorption. After 14 days of continuous induction, the drug resistance index of this system remained below 2, which was significantly lower than that of the gentamicin control group (>16), confirming its ability to effectively delay the development of drug resistance.¹⁴⁰ Meanwhile, van Hengel IAJ et al fabricated silver- and zinc-co-doped titanium dioxide coatings using selective laser melting technology, achieving a bactericidal rate of 99.9% against methicillin-resistant Staphylococcus aureus (MRSA) and complete elimination of drug-resistant bacteria in both in vitro and ex vivo models.⁵⁵ Similarly, the Li X team developed a hydrogel system loaded with minocycline–zinc oxide serum albumin nanoparticles (Mino-ZnO@Alb NPs) and evaluated its therapeutic efficacy in a mouse model of peri-implantitis. After one month of treatment, the Mino-ZnO@Alb NPs group demonstrated significant improvements over the control group across multiple clinical parameters, including bleeding on probing, probing depth, bleeding index, and gingival index. These findings indicate that Mino-ZnO@Alb NPs not only effectively alleviate peri-implant inflammatory responses but also promote soft tissue healing, highlighting their promising therapeutic potential.¹⁴¹

In addition, intelligent nano-drug delivery systems with responsive characteristics (eg., pH, ROS, and temperature sensitivity) can be engineered on implant surfaces to precisely sense changes in the lesion microenvironment and trigger controlled release of antibacterial agents, thereby improving treatment targeting and efficiency. Peri-implantitis lesions typically exhibit an acidic microenvironment, which provides a basis for designing pH-responsive nanocarriers.¹⁴² For example, Liang S et al successfully synthesized zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with vancomycin (Van) and zoledronic acid (ZOL) (VZZ-8 NPs). These nanoparticles remain stable under physiological pH conditions (pH 7.4) but rapidly degrade in acidic environments (pH 5.0), enabling on-demand, synergistic release of zinc ions and vancomycin and thereby enhancing antibacterial efficacy. Moreover, zinc ions released from VZZ-8 NPs significantly enhance the bactericidal efficiency of vancomycin by disrupting bacterial membrane integrity and reducing the effective drug dosage. In vitro experiments demonstrated clearance rates of 93.84 ± 7.38% against MRSA and biofilm inhibition rates of up to 95.36 ± 0.13%. This nanosystem integrates targeted delivery with pH-responsive release, providing an efficient therapeutic strategy for MRSA-related infections (Figure 6B).¹³⁸ Similarly, Huang H et al developed a chitosan-based thermosensitive hydrogel system (ZnO-GO/CS/β-GP) incorporating zinc oxide–graphene oxide (ZnO-GO) composites. In vitro studies showed that both 1% and 3% ZnO-GO/CS/β-GP systems effectively inhibited the activity and biofilm formation of Porphyromonas gingivalis, with the antibacterial rate approaching 100% at a ZnO-GO concentration of 3% (Figure 6C).¹³⁹

An ideal implant surface should simultaneously exhibit antibacterial activity and promote osseointegration. Nano-drug delivery systems can synergistically enhance osseointegration either through their inherent nanotopographical features (eg., TiO₂ nanotubes and nanorod arrays) or by incorporating osteogenic factors (eg., BMP-2), thereby achieving dual functional integration of antibacterial and osteogenic properties. For example, Zeng X et al developed a multifunctional implant surface by constructing silver/PLGA nanocoatings on titanium implants. In vitro studies demonstrated strong antibacterial activity against both MRSA and Pseudomonas aeruginosa, while simultaneously accelerating osteoblast proliferation, maturation, and differentiation. In vivo experiments further confirmed that this coating significantly promoted new bone formation while inhibiting bacterial survival.¹⁴³ In another study, Anushikaa R et al fabricated three-dimensional porous titanium scaffolds using laser sintering technology and loaded them with strontium-doped AgNP-gelatin hydrogels. This composite scaffold exhibited excellent antibacterial performance while significantly upregulating Runx2 gene expression, promoting matrix mineralization, and effectively driving osteoblast differentiation.¹⁴⁴

In summary, nano-drug delivery systems provide an efficient and precise strategy for the prevention and treatment of peri-implantitis through their controllable release kinetics, high drug-loading capacity, and synergistic antibacterial mechanisms. These systems effectively overcome the burst release and late-stage concentration deficiencies associated with traditional coatings and enable on-demand drug release via intelligent responsiveness, thereby enhancing targeting and reducing the risk of drug resistance. Moreover, dual-function designs that integrate antibacterial activity with osteogenic promotion hold substantial promise for improving soft tissue healing and osseointegration.

Design Strategies for Nano-Modified Implant Surfaces

Three-Dimensional Hierarchical Architecture: Spatial Functional Partitioning

Layer-by-layer (LBL) self-assembly technology provides a precisely controllable platform for constructing nano-coatings with spatially functionalized zones on implant surfaces. A common strategy involves the bottom-up design of a three-layer system: the basal interface layer, the functional regulatory layer, and the outer bioactive layer.¹⁴⁵ The primary role of the basal interface layer is to establish stable chemical bonding with the titanium substrate. Studies have demonstrated that introducing reactive functional groups, such as amino or carboxyl groups, onto the substrate surface through silanization or plasma activation significantly enhances the uniformity and adhesion of subsequently deposited polyelectrolyte layers.^146–148 Optimizing the thickness of this layer is critical: insufficient thickness may lead to coating delamination, while excessive thickness may alter the surface topography of the substrate.

The functional regulatory layer serves as the core region conferring antibacterial properties to the implant. This layer achieves nanoscale thickness control through the alternating deposition of positively and negatively charged polyelectrolytes. The thickness of each layer can be precisely modulated by adjusting parameters such as polyelectrolyte concentration, solution pH, ionic strength, and the number of deposition cycles.¹⁴⁹ Multiple factors must be carefully balanced in thickness design. A thicker functional layer can load higher concentrations of antibacterial nanoparticles, enabling sustained release. However, excessive thickness may delay the initial burst release, compromising rapid efficacy during the acute infection phase. Conversely, while a thinner layer may facilitate early cell adhesion, the antibacterial agents may be depleted prematurely, failing to provide long-term protection.¹⁵⁰

The outer bioactive layer is primarily responsible for promoting cell adhesion and tissue integration. This layer often incorporates hydrophilic polymers or extracellular matrix-derived peptides.^151,152 Its thickness must be carefully optimized to balance antibacterial activity and cellular responsiveness. An excessively thick outer layer may physically mask the antibacterial function of the underlying regulatory layer, whereas an overly thin layer may fail to present sufficient recognition signals for effective cell interaction.¹⁵³ For example, Li W et al successfully constructed a chitosan–heparin polyelectrolyte multilayer film system (PEMs) loaded with AgNPs on alkali–heat-treated titanium substrates using LBL self-assembly technology (Figure 7). Their results demonstrated that the silver-loaded nanomultilayer–modified titanium surfaces achieved sustained silver ion release throughout the critical period of mucosal healing (28 days), which not only significantly enhanced antibacterial activity against various pathogenic bacteria but also effectively promoted the adhesion and proliferation of human gingival fibroblasts. This study confirmed that LBL self-assembly is an effective strategy for constructing coatings with long-lasting antibacterial performance and favorable biocompatibility, providing a promising technical pathway for reducing peri-implant microbial infection risk and improving soft tissue sealing quality.¹⁵⁴

Figure 7 Schematic of PEMs construction on titanium substrates using layer-by-layer (LBL) self-assembly. Reprinted from Li W, Yang Y, Zhang H et al Improvements on biological and antimicrobial properties of titanium modified by AgNPs-loaded chitosan-heparin polyelectrolyte multilayers. J Mater Sci Mater Med, 30, 52, Copyright 2019, with permission from Springer Nature.154

Accordingly, the design of the three-layer structure involves a synergistic balance that requires systematic experimental optimization to determine the most effective parameter combinations. Although LBL technology offers significant advantages for constructing nano-modified implant surfaces, its reliance on weak intermolecular interactions presents potential challenges, particularly the sensitivity of coating stability to environmental factors such as pH and ionic strength. Therefore, future research should prioritize the optimization of coating design and fabrication processes to overcome these limitations, thereby enhancing the therapeutic efficacy and clinical translational potential of this technology.

Ratio–Function Effect Adaptation Mechanism

The biological effects of multifunctional composite nano-modified coatings must be proportionally balanced according to their intended clinical applications. Therefore, the relative proportions of nano-components with specific biological functions require careful adjustment. To reduce the incidence of peri-implantitis and ensure long-term implant success, multiple factors must be simultaneously considered, including antibacterial activity, osteogenic potential, biocompatibility, and corrosion resistance. The balance of nanoparticle content is critical for both the safety and efficacy of composite coatings. For instance, nanomaterials such as titanium dioxide and silver nanoparticles may induce oxidative stress responses in both bacteria and host cells, potentially leading to unintended apoptosis of host cells.^155–158

In single-component functional nanoparticle coatings, determining the “optimal” proportion generally follows the classic pharmacological principle of dose-response relationships. Liu X et al fabricated silver-containing hydroxyapatite (Ag-HA) nanocomposite coatings with silver contents of 0%, 1%, 2%, and 5% on Ti6Al4V implant surfaces using laser deposition technology. Antibacterial evaluations demonstrated significant bactericidal activity across all silver-containing coatings. However, cytotoxicity assessments revealed that biocompatibility was strongly dependent on silver content: when silver content reached 5%, cell viability decreased markedly. Comprehensive analysis indicated that the Ag-HA coating containing 2% silver achieved an optimal balance between antibacterial efficacy and cytocompatibility.¹⁵⁹ It is noteworthy that the relationship between antibacterial nanoparticle dosage and biological effects is not strictly linear, underscoring the need for further research to achieve an optimal balance between antibacterial performance and biocompatibility.

When multiple functional nanoparticles (such as AgNPs, ZnO, Sr²⁺, and BMP-2) are co-incorporated into a single coating, the proportional relationships between components exert a more complex influence on overall coating performance. These components may exhibit synergistic, additive, or antagonistic effects, necessitating systematic experimental design to determine optimal ratios.¹⁶⁰ The oral cavity represents a complex physiological-mechanical coupled system. Dynamically fluctuating pH levels, enzymatic activity, fluid shear forces, and cyclic masticatory loading collectively shape the unique microenvironment at the implant surface, continuously influencing the degradation of nano-coatings and underlying metal substrates.^161,162 Under these conditions, the initial concentration and spatial distribution of functional components directly determine their release kinetics. When degradation occurs too rapidly, although bioactive ion release may be accelerated to quickly establish an antibacterial or osteogenic microenvironment, this can compromise coating structural integrity, induce cytotoxicity due to excessive local ion concentrations, and weaken implant mechanical properties. Conversely, overly slow degradation may preserve mechanical stability but fail to achieve effective bioactive ion concentrations during the critical postoperative periods for infection prevention and osseointegration, thereby diminishing antibacterial and osteogenic efficacy.¹⁶³ Furthermore, the temporal sequence of multifunctional release must be considered. Different functional requirements dominate at various stages following implant placement: the immediate to 72-hour postoperative period requires rapid antibacterial action to eliminate early colonizing bacteria; the subsequent 1–4 weeks require sustained bacteriostatic effects while initiating osteogenic differentiation; after 4 weeks, maintenance of an osteoinductive microenvironment is necessary. Therefore, the optimal ratio is not merely a static concentration concept but must align with release kinetics. Gradient distribution or core-shell structural designs can achieve a “fast-then-slow” sequential release pattern. For example, Chen Y et al constructed zinc/strontium co-doped nanorod coatings that achieved temporally controlled release of Zn²⁺ and Sr²⁺: Zn²⁺ was released rapidly in the early stage to exert antibacterial effects, while Sr²⁺ was released continuously during the mid-to-late bone healing phase to promote osteogenic differentiation.¹⁶³

However, current studies employ diverse cell models, bacterial strains, culture conditions, and evaluation indicators, making it difficult to compare “optimal ratios” across different studies. Future efforts should establish standardized in vitro evaluation systems and functional component response databases. By integrating machine learning algorithms, component-structure-performance prediction models can be constructed, thereby advancing coating design from “trial-and-error optimization” toward “rational design”.

Intelligent Responsiveness: Microenvironment–Release Synergy

The core design principle of intelligent responsive nano-modified implants lies in achieving precise, controlled release of antibacterial agents by sensing changes in specific biomarkers within the peri-implant infection microenvironment. These systems utilize characteristic microenvironmental signals—such as acidic pH, overexpressed proteases, elevated ROS levels, and local temperature variations—as intelligent triggers to dynamically regulate the on-demand release of antibacterial agents, metal ions, or bioactive molecules. This strategy establishes a synergistic linkage between microenvironmental cues and drug release behavior.^61,62

In pH-responsive system design, proton-sensitive functional groups such as hydrazone bonds, ketals, and carboxyl groups are commonly employed. These groups remain stable under neutral physiological conditions but undergo protonation or cleavage in acidic inflammatory environments (pH 5.5–6.5), thereby triggering the release of encapsulated antibacterial agents.¹⁶⁴ For instance, Zhang L et al developed a pH-responsive titanium-based GGO composite coating using a Schiff base reaction to crosslink oxidized sodium alginate with gentamicin and gelatin, forming a uniform coating on titanium bone plates. To further enhance long-term stability, glutaraldehyde was introduced for secondary crosslinking. This dual-crosslinked structure remained stable at neutral pH but enabled controlled gentamicin release via the pH sensitivity of imine bonds under acidic conditions, resulting in sustained antibacterial activity.¹⁶⁵

Beyond pH responsiveness, enzyme-responsive strategies are also widely applied in intelligent antibacterial system design. Yuan Z et al modified titanium substrates by using vancomycin-loaded TiO₂ nanotube arrays as drug reservoirs, which were subsequently sealed with a composite film composed of hyaluronic acid–dopamine (HA-DOP) and chitosan–dopamine (CHI-DOP). This design exploits hyaluronidase secreted by pathogenic bacteria as a specific biological trigger to initiate coating degradation, thereby inducing rapid in situ release of vancomycin from the nanotubes and achieving precise and efficient bacterial eradication.¹⁶⁶

ROS-responsive mechanisms represent another important controlled-release strategy and typically involve ROS-sensitive groups such as thioethers or selenides. Lu MM et al constructed a dual-responsive delivery platform based on biodegradable mesoporous silica nanoparticles (MSNs) capable of simultaneously sensing excessive ROS and acidic pH in the oral biofilm microenvironment. In this system, thioketal bonds were used to anchor cyclodextrin “gatekeepers” at nanopore outlets containing chlorhexidine (CHX), enabling ROS-triggered CHX release. Meanwhile, AgNPs were immobilized on the nanoparticle surface via coordination bonds to allow pH-triggered release of silver ions (Ag⁺). In vitro experiments demonstrated that this system underwent degradation under ROS-rich and acidic conditions, synergistically releasing CHX and Ag⁺ and exhibiting strong eradication effects against both single-species and dual-species biofilms formed by Streptococcus mutans and Fusobacterium nucleatum.¹⁶⁷

It is important to note that the peri-implantitis microenvironment is highly complex and dynamically evolving, which may limit the effectiveness of single-stimulus responsive systems. Consequently, the design of intelligent responsive coatings increasingly emphasizes the integration of multiple response mechanisms. By combining pH sensitivity, enzyme-responsive substrates, and ROS-triggered signals within a single nanosystem, it becomes possible to more accurately identify infection states, minimize erroneous drug release triggered by isolated signals, and further enhance the specificity and safety of peri-implantitis prevention and treatment.

Preparation Processes and Clinical Benefits

The excellent performance of intelligent responsive coatings on implant surfaces ultimately depends on precise preparation processes, and the selection and optimization of fabrication routes directly determine their clinical benefits. The choice of preparation methods and manufacturing parameters not only affects the microstructure and physicochemical properties of the coatings but is also closely associated with their long-term stability, biosafety, and functional durability in the complex oral environment. Consequently, coating fabrication represents a critical determinant of success or failure in peri-implantitis prevention and treatment.¹⁶⁸ As maxillofacial implants are required to withstand masticatory loading, implant surface nano-modified coatings must exhibit excellent mechanical properties and long-term stability. Among various preparation techniques, electrochemical deposition is widely employed to fabricate high-performance composite coatings due to its highly controllable parameters (eg., current density, electrolyte temperature, and pH), which allow precise regulation of coating thickness, porosity, and nanoparticle spatial distribution.^169–171 For example, Yin L prepared a TNTs/(CS-Gel-Ag-ZnO) composite coating with excellent antibacterial properties using electrodeposition combined with anodization. The results demonstrated that AgNPs were firmly anchored and uniformly distributed within the TNTs, and the silver ion release rate was significantly reduced, thereby lowering cytotoxicity and prolonging the service life of the coating.¹⁷² For intelligent coating systems requiring three-dimensional hierarchical architectures and multiple responsive functions, layer-by-layer (LBL) self-assembly has become an important strategy for achieving functional integration owing to its precise control over film thickness and chemical composition.^173–176 Nevertheless, LBL technology currently faces challenges, including limited availability of specialized functional material systems and relatively complex preparation procedures. Its future potential for clinical translation will largely depend on continued innovation in material design and process optimization.

Current Challenges and Future Directions

Despite the considerable promise of nano-modified implant surfaces demonstrated in preclinical studies, their translation from laboratory research to routine clinical practice faces multiple obstacles. Understanding and addressing these challenges is essential for identifying future research directions and advancing this field.

Resistance Risks and Long-Term Safety

Although nanomaterials significantly enhance antibacterial efficacy, their long-term ecological effects on the oral microbiome remain inadequately studied. Sun G et al noted that the antimicrobial action of nanomaterials is often non-selective, potentially inhibiting or eliminating beneficial commensal bacteria while clearing pathogens.¹⁷⁷ This non-specific antibacterial effect may lead to reduced microbial diversity, altered community structure, and subsequent disruption of oral microecological balance. Bacterial adaptive resistance to nanomaterials has been confirmed by multiple studies. Traditional views held that the multi-target mechanisms of nanomaterials make them less prone to inducing resistance. However, recent studies have challenged this assumption. Suchánková L et al systematically reviewed bacterial adaptation mechanisms to silver and metal oxide nanomaterials, clearly demonstrating that bacteria can employ multiple strategies to reduce their susceptibility to nanomaterials. These adaptive mechanisms include genetic adaptations (eg., efflux pump upregulation, gene mutations), biomolecule production (eg., flagellin, extracellular polysaccharides, protein coronas), and structural changes (eg., altered cell morphology, cell wall thickening, enhanced motility, and modified membrane permeability).¹⁷⁸ Mann R et al revealed complex adaptation phenomena in environments where nanoparticles and antibiotics coexist. Their study found that under the selective pressure of simultaneous exposure to silver nanoparticles and antibiotics, pathogenic bacteria can develop cross-resistance, further complicating infection control.¹⁷⁹

Furthermore, the cytotoxicity of nano-modified coatings on implant surfaces also warrants attention. Gulati K et al systematically explored the double-edged sword effect of doped titanium implants, highlighting the delicate balance between therapeutic efficacy and toxicity. Although metallic nanoparticles such as silver, copper, and zinc exhibit potent antibacterial activity, their non-specific release may induce local cytotoxicity, genotoxicity, and pro-inflammatory responses, thereby impairing osteoblast function and soft tissue integration.¹⁸⁰ Beyond local release, the complex oral environment poses challenges to the long-term stability of implant coatings. Mechanical failure or corrosion can lead to coating degradation, releasing nanoparticles or metal ions from the implant surface into surrounding tissues and even the circulatory system. A review by Miller RS et al indicated that common metal-containing nanoparticles, including silver, titanium dioxide, and zinc oxide, can distribute systemically via blood circulation and accumulate in distant organs such as the liver, spleen, kidneys, and brain. Through the generation of reactive oxygen species and activation of inflammatory cascades, these nanoparticles may cause potential damage to multiple organ systems, including the respiratory, cardiovascular, nervous, and immune systems.¹⁸¹ Of note, most existing studies have employed cellular and in vitro models, with findings primarily reflecting short-term exposure effects. Reliable long-term follow-up data remain scarce, leaving the metabolic kinetics, accumulation thresholds, and potential chronic toxicity of nanoparticles in humans largely undetermined.

Clinical Translation Challenges

The clinical translation of nano-modified implants is first confronted with regulatory complexity. As Class III medical devices, their approval requires comprehensive preclinical safety and efficacy data. However, internationally accepted standardized testing protocols for evaluating nanomaterial biocompatibility, in vivo degradation behavior, immunotoxicity, and genotoxicity remain unavailable. Variations in requirements for nanomaterial characterization, long-term release kinetics, and biodistribution across different regulatory agencies not only prolong approval timelines but also substantially increase research and development costs.

Scalability and quality control of fabrication processes present major technical challenges. Many nanocoating techniques successfully developed at the laboratory scale, such as electron beam lithography, chemical vapor deposition, and layer-by-layer assembly, face difficulties in reproducibility and batch-to-batch consistency when scaled up for industrial production. The uniformity, thickness control, and long-term stability of coating adhesion to the substrate are particularly susceptible to compromise during large-scale manufacturing. Furthermore, high fabrication costs and uncertain cost-effectiveness ratios further limit widespread application of nano-modified implants. The specialized equipment, cleanroom environments, and complex process controls required for advanced nanofabrication technologies result in production costs substantially higher than those of conventional implants.

Patient variability also warrants attention regarding coating performance. In clinical practice, factors such as patients’ systemic health conditions, oral microecological environment, smoking habits, and oral hygiene maintenance capacity may significantly influence the in vivo degradation behavior and biological effects of nano-coatings. Most current studies employ standardized animal models or healthy cell lines, failing to adequately simulate the complex individual variations encountered in real clinical scenarios. Consequently, the efficacy of nano-coatings in clinical applications may exhibit considerable variability, necessitating stratified analysis or personalized design approaches.

Future Research Directions

To address these challenges, future research should advance in several directions. First, efforts should focus on developing intelligent nano-modified systems capable of dynamically responding to the complex oral environment. The oral cavity is characterized by fluctuating pH, variable enzymatic activity, masticatory loading, and salivary protein adsorption, all of which influence the degradation behavior and ion release kinetics of nano-coatings. Future smart implant systems should be able to sense and respond to biological signals such as local pH changes, specific enzymes, reactive oxygen species levels, or temperature variations, thereby triggering precise on-demand release of antibacterial agents. For instance, pH-responsive coatings can selectively degrade within the acidic microenvironment resulting from infection, achieving localized drug release; enzyme-responsive coatings can utilize pathogen-secreted enzymes to trigger drug release, enhancing therapeutic precision. Integrating such responsive features with advanced drug delivery systems represents a key strategy for improving the efficacy of peri-implantitis prevention and treatment. For example, Ma Z et al fabricated porous titanium rods using 3D printing technology as carriers for vancomycin-loaded mPEG750-b-PCL2500 thermosensitive hydrogel, coated with an outer polycaprolactone membrane to construct an intelligent antibacterial coating system.¹⁸² The outer PCL membrane inhibits bacterial biofilm formation in the early stage of infection and rapidly degrades upon exposure to bacterial lipase, triggering on-demand vancomycin release, while the thermosensitive hydrogel ensures sustained and stable drug release. In vitro experiments confirmed excellent antibacterial activity and biocompatibility of this system, providing a feasible technical pathway for the design and development of intelligent nano-modified systems for implant surfaces.

Second, emphasis should be placed on constructing multifunctional integrated coatings that synergistically achieve multiple biological objectives, including antibacterial activity, anti-inflammatory effects, and osteogenic promotion. Compared with natural teeth, peri-implant tissues are more susceptible to infection and progressive bone loss. Merely eliminating biofilms is insufficient to reverse the local inflammatory microenvironment or ensure long-term osseointegration. Therefore, while imparting implants with durable antibacterial properties, it is essential to simultaneously optimize their biocompatibility and osteogenic potential. Achieving spatiotemporal synergy between antibacterial function and osteogenic activity through rational design of coating composition and structure will be a key focus of future research.

To overcome current research limitations, clinical translational research should be vigorously advanced. It is important to note that most studies discussed above fall within the realm of in vitro experiments, and their results may differ substantially from outcomes observed in complex in vivo environments. Therefore, establishing standardized evaluation systems is crucial. Long-term in vitro co-culture models and standardized animal models need to be developed. Microbiome indicators should be integrated into safety evaluation frameworks to dynamically monitor the composition and functional changes of peri-implant microbial communities, providing scientific basis for developing selective antibacterial strategies. Future research should progressively initiate well-designed clinical trials to accumulate more reliable in vivo data, systematically evaluating the long-term efficacy and safety of nano-modified implants under real oral conditions.

Conclusion

Nano-modification technologies for implant surfaces are driving a paradigm shift in the prevention and treatment of peri-implantitis, transitioning from traditional “empirical debridement and broad-spectrum antibacterial” approaches toward systematic intervention strategies characterized by “cross-scale modulation, multi-mechanism synergy, and microenvironmental responsiveness.” This review summarizes the antibacterial mechanisms, coating design strategies, and biological effects of nano-modification technologies for peri-implantitis management. Extensive in vitro and animal studies have demonstrated that nano-modified implant surfaces can effectively inhibit early pathogen adhesion and biofilm formation, exhibiting significant antibacterial potential. These findings provide strong support for reducing peri-implant infection risks and improving long-term implant survival rates.

However, no single nanomaterial system can simultaneously satisfy the multiple requirements of high antibacterial efficacy, osteogenic promotion, long-term stability, and low systemic toxicity. Therefore, the development of novel intelligent responsive and multifunctional implant coating systems remains a core direction for future research. Although related studies have achieved significant progress and demonstrated promising prospects in vitro, clinical implementation remains a future endeavor. Establishing standardized safety evaluation systems and conducting well-designed clinical trials are essential to accelerate the translation from laboratory research to clinical application, ultimately providing effective solutions for the prevention and treatment of peri-implantitis.