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. 2025 Dec 15;17(12):9531–9541. doi: 10.62347/SWNY2831

Analysis of bioglass/cerium dioxide nanocoating and its antibacterial properties for the restoration of hard tissue around oral titanium implants

Rui Chen 1, Yudong Jia 2, Xiaoxu Ren 3, Gang Guo 3
PMCID: PMC12808076  PMID: 41552326

Abstract

Objective: To investigate peri-implant hard tissue regeneration by developing a novel titanium (Ti) implant coated with a composite nanocoating of bioglass (BG) and cerium dioxide (CeO2). Methods: The BG/CeO2 composite coating was fabricated on Ti implants using liquid-feed flame spray pyrolysis. The coating’s morphology and composition were characterized by scanning electron microscopy and X-ray diffraction. Its antibacterial efficacy was assessed against Porphyromonas gingivalis (P. gingivalis). The cytocompatibility, osteogenic differentiation, and mineralization potential were evaluated using human dental pulp stem cells (DPSCs). Additionally, rabbit mandibular defect models were established to investigate the anti-inflammatory, antioxidant, and osteogenic properties of the implants in vivo. Results: The CeO2 nanocoatings exhibited significant antibacterial activity against P. gingivalis while demonstrating excellent biocompatibility and a marked stimulation of DPSC proliferation. The CeO2/BG-Ti implants were more effective in enhancing DPSC activity and upregulating the expression of osteogenesis-related proteins than control groups. In rabbit models, the CeO2/BG-Ti implants effectively mitigated oxidative stress and reduced the secretion of inflammatory factors, thereby alleviating the post-operative inflammatory response. Furthermore, improved bone healing and enhanced new bone formation were observed around the CeO2/BG-Ti implants, leading to superior implant stability and osseointegration. Conclusions: The CeO2/BG-Ti composite implants demonstrate considerable potential for clinical use in oral implantology, offering enhanced antibacterial, anti-inflammatory, and osteogenic benefits.

Keywords: Bioglass, cerium dioxide, titanium implants, nanoparticles, osseointegration, antibacterial, oral cavity

Introduction

Titanium (Ti) implants have revolutionized dentistry due to their favorable biocompatibility and mechanical properties, with widespread applications including single-tooth replacements, full-arch prosthetic support, and orthodontic anchorage [1-6]. These implants effectively restore masticatory function, phonetics, and aesthetics, significantly improving patients’ quality of life. However, implant failure remains a concern, often resulting from poor osseointegration, peri-implantitis, biomechanical overloading, or insufficient bone volume [7,8]. Such complications may lead to implant loosening or loss, necessitating additional surgical intervention, and increasing patient burden [9,10]. Therefore, enhancing the long-term stability and biological performance of Ti implants is critically important.

Recent advances in nanotechnology have led to the development of various nanocoatings to improve implant osseointegration. Among them, bioglass (BG) is a biomaterial commonly used for the repair of bone defects, offering several benefits and advancements in the field of implant dentistry [11]. Relevant studies have found that BG has the unique property of bonding with bone tissue when it comes into contact with bodily fluids, promoting faster and stronger osseointegration between the implant and the surrounding bone [12]. Moreover, it can promote the formation of new bone tissue in the implant site, which is particularly beneficial in cases with insufficient bone volume or compromised bone quality [13]. Nevertheless, it’s important to note that bacterial colonization and infection around the implant site is a key cause leading to implant failure, such as peri-implantitis. Thus, further optimization of BG composition is needed to incorporate effective antibacterial function.

Cerium dioxide (CeO2) nanoparticles (NPs) have recently emerged as a promising bioactive agent for implant modification due to their beneficial effects. For example, Ceria NPs possess unique antioxidant properties, which can enhance the longevity and performance of Ti implants [14]. In addition, it has been found that Ceria NPs have demonstrated antibacterial properties against various bacterial strains commonly associated with implant-related infections, which can help prevent or minimize the risk of implant-associated infection [15]. Based on this rationale, we proposed that incorporating CeO2 into a BG-based coating on Ti implants could synergistically enhance antibacterial capacity while supporting osseointegration.

At present, studies on the use of CeO2 and BG in Ti implants are still in early stages, and more are needed to explain their potential benefits and long-term effects. This study aimed to investigate whether it is possible to create a favorable environment for osseointegration by modifying the implant surface with CeO2 and BG, thereby reducing the risk of bacterial colonization and promoting better tissue integration.

Materials and methods

Preparation of CeO2/BG-Ti implant

The CeO2/BG hybrid NPs were fabricated and applied to Ti implants by a two-step process based on liquid-feed flame spray pyrolysis (LF-FSP) [16]. First, in the synthesis step, a precursor solution - comprising 68 wt% cerium(III) nitrate, 11 wt% calcium acetylacetonate hydrate, 13 wt% sodium 2-ethylhexanoate, 2 wt% tributyl phosphate, and 6 wt% hexamethyldisiloxane in tetrahydrofuran (THF) (yielding a final CeO2 to BG mass ratio of ~1:0.5) - was fed at 5 mL/min into a water-cooled nozzle, dispersed by O2 (5 L/min), and ignited by a CH4/O2 flame. Ti disks were placed 6 cm above the flame for 25 s to directly deposit the CeO2/BG NPs. Then, during the deposition step, collected NPs were first collected on a filter, dispersed in a mixture of water, acetylacetone, and Triton X-100, and then was spin-coated onto the Ti implant surface using a spin-coater (VTC-100, Kejing Automation Equipment Co., Ltd., Shenyang, China) at 1000 rpm for 60 s. Pure CeO2 and BG control coatings were prepared separately using analogous methods, with the following precursor compositions: CeO2: 100 wt% cerium(III) 2-ethylhexanoate in THF. BG: 40 wt% calcium acetylacetonate hydrate, 37 wt% sodium 2-ethylhexanoate, 6 wt% tributyl phosphate, 17 wt% hexamethyldisiloxane in THF (Figure 1).

Figure 1.

Figure 1

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Mechanism of CeO2/BG Ti implants for peri-implant hard tissue recovery. CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium.

Cell culture

Human dental pulp stem cells (DPSCs, CP-H231) were selected to study the osteogenic properties of CeO2 in vitro. DPSCs were cultured in a 24-well plate with their special medium (CM-H231) in a cell incubator for 24 h. The cultured DPSCs were diluted to 1×106/ml for standby. The cells and cell culture media used were purchased from Wuhan Procell Life Technology Co., Ltd.

Preparation of CeO2 suspensions

The CeO2 NPs were dissolved in 0.9% NaCl solution and subsequently sonicated for 2 min at 0°C to prepare the CeO2 suspension, and the CeO2 suspension was diluted to 25%, 50% and 100% concentrations.

Detection of physicochemical properties of CeO2/BG-Ti

The appearance of CeO2 NPs

The shape and size of the CeO2 NPs were examined by scanning electron microscope (SEM, Sigma, Jena, Germany).

X-ray diffractometer of CeO2/BG-Ti

To observe the composition of the surface coating of Ti implants, X-ray diffractometer (XRD, POWDIX 600/300, Beijing Oubeier Scientific Instrument Co., Ltd.) was used to check its characterization.

CeO2 antibacterial property testing

Porphyromonas gingivalis (P. gingivalis, ATCCBAA-3083, Shanghai Conservation Biotechnology Center, China) was selected for antibacterial test. P. gingivalis was cultured in Columbia blood tablet (CA-B) (BHY-2132, Shanghai Boohoo Biotechnology Co., Ltd., China) under 37°C, 80% N2, 10% CO2, and 10% H2 for 72 h. The colonies were then diluted to a concentration of 1 × 106 CFU/mL by serial dilution and prepared for use. 1 ml of P. gingivalis suspension was cultured in Columbia blood tablet, and divided into control (without any intervention) and CeO2 groups (treated with 25%, 50%, and 100% CeO2 suspensions). Activation state of P. gingivalis was tested by live/dead bacterial kit (04511, Sigma, USA), and the surviving bacteria are stained with green fluorescence and observed with a fluorescent microscope colored green and fluoresced and observed with a confocal microscope (SP8, Leica, Wetzlar, Germany).

Meanwhile, intracellular reactive oxygen species (ROS) levels in P. gingivalis were detected using the fluorescent probe DCFH-DA (Beyotime Biotechnology, China).

CeO2 biocompatibility testing

1 ml of DPSCs dilution was inoculated on 12-well plates and divided into control (without any intervention) and CeO2 groups (treated with 25%, 50% and 100% CeO2 suspensions), with 3 replicate wells in each group. 24 h after incubation, Anti-filamentous actin antibody [NH3] (ab205) was added to label the viable cytoskeleton and fluorescein isothiocyanate (FITC, ab6717) was added as a fluorescent secondary antibody, while 4’,6-diamidino-2-phenylindole dihydrochloride (DAPI, ab285390) was used to stain the nuclei of the viable cells. Finally, the fluorescent staining of the cells in each group was observed using a confocal microscope. All reagents were purchased from Abcam, Waltham, MA, USA.

DPSCs activity assay

1 ml of DPSCs dilution was inoculated in a 12-well plate with its special culture medium and divided into Ti (treated with Ti implant), BG-Ti (treated with BG-Ti implant), and CeO2/BG-Ti groups (treated with CeO2/BG-Ti implant) with 3 replicate wells. After incubation at 37°, 5% CO2 for 24 h, fluorescent staining of the surviving cells in each group was examined using the same method described in section 2.4.4.

DPSCs mineralization function assay

1 ml of DPSCs dilution was inoculated in 12-well plate and divided into Ti [osteoinduction medium (HUXDP-90021, Saiye Biotechnology Co., Ltd., Suzhou, China) + Ti implant], BG-Ti (osteoinduction medium + BG-Ti implant), and CeO2/BG-Ti groups (osteoinduction medium + CeO2/BG-Ti implant) with three replicate wells in each group. After 7 days of incubation, the levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and type I collagen (Col I) were measured in each group. Briefly, Anti-RUNX2 (ab192256), Anti-ALP (ab224335), and Anti-Col I (ab34710) were used to label the above osteogenic proteins in cells, and FITC, ALP (ab6722), and Alexa Fluor® 405 (ab175652) were added as fluorescent secondary antibodies. Finally, the fluorescent staining was observed in each group using confocal microscopy. Meanwhile, relative expression of the above indexes in each group was quantitatively detected by polymerase chain reaction (PCR) (Table 1). All reagents used were purchased from Abcam.

Table 1.

PCR primer information

F primer R primer
RUNX2 5’-TTCAACGATCTGAGATTTGTGGG-3’ 5’-GGATGAGGAATGCGCCCTA-3’
ALP 5’-AACCCAGACACAAGCATTCC-3’ 5’-CCAGCAAGAAGAAGCCTTTG-3’
Col I 5’-CACCCTCAAGAGCCTGAGTC-3’ 5’-CGGGCTGATGTACCAGTTCT-3’
β-actin 5’-CTGGCACCACACCTTCTACA-3’ 5’-GGTACGACCAGAGGCATACA-3’
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PCR: Polymerase chain reaction; RUNX2: Runt-related transcription factor 2; ALP: Alkaline phosphatase; Col I: Type I collagen.

Implant placement surgery

36 New Zealand white rabbits weighted 4.5-5 kg were chosen for animal tests. The rabbits were randomly divided into Ti, BG-Ti, and CeO2/BG-Ti groups, with 12 rabbits in each group. After general anesthesia with 3% pentobarbital sodium, the rabbits were gingivally separated and their two mandibular anterior teeth were extracted, followed by insertion of Ti, BG-Ti, and CeO2/BG-Ti implants into their sockets, and final suturing of the gingiva to cover the implants. Post-operative intramuscular penicillin sodium was administered for 3 consecutive days to combat infection and the maxillary anterior teeth were polished weekly to avoid damage to the wound.

Detection of inflammatory response

At 3 weeks post-operation, three randomly selected rabbits from each group were euthanized, and their mandibles were dissected. Bone blocks containing the implants were meticulously sectioned. After careful removal of the implants, all surrounding soft and hard tissues within the sockets were harvested using a sterile curette. The acquired tissue specimens were thoroughly homogenized and centrifuged to obtain the supernatant for subsequent analysis. Levels of IL-1β (ab197742), IL-6 (ab222503), and TNF-α (ab208348) were then measured by ELISA. All kits were purchased from Abcam.

Detection of oxidative stress

As described in section 2.8, the acquired tissue specimens were thoroughly homogenized and centrifuged to obtain the supernatant. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were then measured by ELISA. The corresponding kits were purchased from Nanjing Jiancheng BioEngineering Institute.

Peri-implant osteogenesis test

New Zealand rabbits in each group were randomly divided into 1-, 2-, and 3- month groups and sacrificed at 1, 2, and 3 months postoperatively to obtain peri-implant mandibular bone specimens respectively. Twenty-seven mandibular bone samples were then scanned using micro-CT (SKYSCAN 1276, BRUKER, Karlsruhe, Germany) and the accompanying Java software was used to calculate the bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and total porosity [Po(tot)] of the interest area 1 mm from the implant to quantitatively assess the healing of the peri-implant bone tissue. During the measurement, the irregularities in the image were manually selected to exclude the cortical bone in the interest area and to retain only the trabecular for evaluation.

Statistical analysis

All data were analyzed using GraphPad Prism 7 (GraphPad Software, USA) and are presented as mean ± standard deviation (SD). Differences between two groups were assessed using the two-tailed Student’s t-test, while one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was used for multiple group comparisons. Statistical significance was set at *P* < 0.05.

Results

Physicochemical property testing

The average particle size of CeO2 NPs was approximately 10-20 nm (Figure 2A). To investigate the composition of the Ti implant surface coating, the characterization of the coating was analyzed by XRD. The results showed that the CeO2, BG, and CeO2/BG coatings all had a clear Ti background, with the BG coating only appearing as a visible small angular diffraction peak, indicating that most of the BG did not remain in the crystalline state. In contrast, the CeO2 and CeO2/BG coatings showed several characteristic diffraction peaks, suggesting that CeO2 formed a crystalline phase in the coating (Figure 2B).

Figure 2.

Figure 2

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SEM of CeO2 nanoparticles (A) and XRD of Ti implants with different coatings (B). Scale bar: 50 nm. SEM: Scanning electron microscope; CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium; XRD: X-ray diffractometer.

CeO2 could effectively inhibit P. gingivalis proliferation

The staining of surviving P. gingivalis was observed by fluorescence microscopy, and it was found that CeO2 could effectively inhibit the activity of P. gingivalis and inhibit their proliferation, and its inhibitory property was further enhanced with increasing concentration (Figure 3A-D). As the concentration of the CeO2 suspension increased, the intracellular ROS level in bacteria rose correspondingly (Figure 3E-H). Thus, CeO2 has marked antibacterial properties and is concentration-dependent.

Figure 3.

Figure 3

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Detection of CeO2 nanoparticles’ antibacterial activity. A-D: Fluorescent staining of dead P. gingivalis in the control and CeO2 groups with different concentrations, 10×. E-H: Fluorescent staining of ROS in the control and CeO2 groups with different concentrations, 10×. Scale bar: 10 μm. CeO2: Cerium dioxide; ROS: Reactive oxygen species.

CeO2 showed good biocompatibility

Fluorescence microscopic observation showed that the addition of CeO2 effectively enhanced the activity of DPSCs compared to those cultured alone, and their number further increased with increasing concentration of CeO2 suspensions (Figure 4). Thus, CeO2 is biocompatible and can effectively enhance DPSC activity in a concentration-dependent manner.

Figure 4.

Figure 4

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Fluorescent staining of DPSC nuclei, F-actin, and both combined in the control (A-C) and 25% (D-F), 50% (G-I), and 100% (J-L) CeO2 groups, 40×. Scale bar: 10 μm. DPSC: Dental pulp stem cell; FITC: Fluorescein isothiocyanate; DAPI: 4’,6-diamidino-2-phenylindole dihydrochloride; CeO2: Cerium dioxide.

CeO2/BG-Ti could better enhance DPSCs activity

Under fluorescence microscopy, cell adhesion was observed on the surface of Ti implants covered with different coatings. More DPSCs were observed on the surface of BG- and CeO2/BG-Ti implants compared to Ti implants alone, especially in the CeO2/BG-Ti group (Figure 5). Therefore, CeO2/BG-Ti can more effectively promote DPSC proliferation.

Figure 5.

Figure 5

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Fluorescent staining of DPSC nuclei, F-actin, and both combined in the Ti (A-C), BG-Ti (D-F), and CeO2/BG-Ti (G-I) groups, 40×. Scale bar: 10 μm. DPSC: Dental pulp stem cell; FITC: Fluorescein isothiocyanate; DAPI: 4’,6-diamidino-2-phenylindole dihydrochloride; CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium.

CeO2/BG-Ti could better enhance the mineralization of DPSCs

To assess the osteoinductive function of CeO2/BG, we examined the expression of relevant osteogenic proteins in DPSCs. We found that the expression levels of RUNX 2, ALP, and COL I were markedly increased in the BG- and CeO2/BG-Ti groups compared to DPSCs cultured with Ti implants, especially in the CeO2/BG-Ti group (Figure 6A-I). The quantitative PCR analysis of the above indicators in each group also demonstrated the same results (Figure 6J). Thus, CeO2/BG-Ti could better enhance the mineralization function of DPSCs and promote bone tissue repair.

Figure 6.

Figure 6

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Detection of DPSC mineralization. A-C: RUNX2 fluorescent staining in DPSCs cultured with Ti, BG-Ti, or CeO2/BG-Ti implants, 40×. D-F: ALP fluorescent staining in DPSCs cultured with Ti, BG-Ti, or CeO2/BG-Ti implants, 40×. G-I: COL I fluorescent staining in DPSCs cultured with Ti, BG-Ti, or CeO2/BG-Ti implants, 40×. J: The quantitative PCR analysis of RUNX2, ALP, and COL I. Scale bar: 20 μm. **P < 0.01. n=3. DPSC: Dental pulp stem cell; RUNX2: Runt-related transcription factor 2; ALP: Alkaline phosphatase; Col I: Type I collagen; CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium; PCR: Polymerase chain reaction.

CeO2/BG-Ti implants effectively inhibited the inflammatory response

After implantation of different Ti implants, the levels of IL-1β, IL-6, and TNF-α were higher in rabbits in the Ti and BG/Ti groups than in the CeO2/BG-Ti group (Figure 7). Therefore, the CeO2/BG coating could better suppress the inflammatory response after implant placement.

Figure 7.

Figure 7

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Comparison of IL-1β (A), IL-6 (B), and TNF-α (C) levels in rabbit models treated with Ti, BG/Ti, and CeO2/BG-Ti implants. #P > 0.05, **P < 0.01. n=3. CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium.

CeO2/BG-Ti implants could effectively inhibit oxidative stress

Oxidative stress levels provide a useful assessment of the occurrence of inflammatory responses in vivo. SOD and TAC levels in rabbits were markedly lower in the Ti and BG/Ti groups than in the CeO2/BG-Ti group, in contrast to the significant increase in MDA levels that occurred (Figure 8). Thus, the CeO2/BG coating is effective in suppressing the degree of oxidative stress after implant insertion.

Figure 8.

Figure 8

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Comparison of SOD (A), TAC (B), and MDA (C) levels in rabbit models treated with Ti, BG/Ti, and CeO2/BG-Ti implants. #P > 0.05, **P < 0.01. n=3. SOD: Superoxide dismutase; TAC: Total antioxidant capacity; MDA: Malondialdehyde; CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium; Prot: Protein.

CeO2/BG-Ti can best promote peri-implant hard tissue recovery

By observing the peri-implant bone tissue by micro-CT, we found that BV/TV and Tb.Th were markedly higher in the area 1 mm from the BG- and CeO2/BG-Ti implants compared to the Ti implants, and that these indicators continued to increase with time of implantation, especially in the CeO2/BG-Ti group (Figure 9A-D). In contrast, Po(tot) was markedly lower in the BG- and CeO2/BG-Ti groups than in the Ti group and continued to decrease with increasing implantation time, especially in the CeO2/BG-Ti group (Figure 9E, 9F). CeO2/BG-Ti therefore better promotes the regeneration and maturation of the bone tissue around the implant for its better stability.

Figure 9.

Figure 9

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Comparison of peri-implant hard tissue recovery in terms of BV/TV (A, B), Tb.Th (C, D), and Po(tot) (E, F) in rabbit models treated with Ti, BG/Ti, and CeO2/BG-Ti implants at 1, 2, and 3 months. **P < 0.01. n=3. BV/TV: Bone volume fraction; Tb.Th: Trabecular thickness; Po(tot): Porosity; CeO2: Cerium dioxide; BG: Bioglass; Ti: Titanium.

Discussion

In this study, we developed a novel CeO2/BG composite coating for titanium implants to enhance osseointegration - the direct structural and functional connection between living bone and the implant surface. Our findings demonstrate that this coating exhibits excellent antibacterial properties, promotes stem cell proliferation and osteogenic differentiation, and reduces inflammatory and oxidative stress in vivo, collectively contributing to improved bone regeneration and implant stability.

Physicochemical characterization confirmed the successful synthesis of CeO2 nanoparticles with a size of approximately 10-20 nm and the formation of a crystalline CeO2 phase within the composite coating. The antibacterial assays revealed that CeO2 effectively inhibited the growth of P. gingivalis in a concentration-dependent manner. Li et al. [17] also found that CeO2 could effectively inhibit the proliferation of various bacteria and had good antibacterial properties. The potent antibacterial activity observed in our study can be primarily attributed to the ROS generation mediated by CeO2 NPs. Our experimental data provide direct evidence that intracellular ROS levels in P. gingivalis increased significantly in a dose-dependent manner with the concentration of CeO2 NPs. This is consistent with the established ability of CeO2 NPs to cycle between Ce3+ and Ce4+ oxidation states, catalyzing the production of superoxide and hydroxyl radicals [18]. These highly reactive species can inflict severe damage to essential bacterial components, including DNA, proteins, and lipids. Furthermore, we speculate that the observed antibacterial effect is likely exacerbated by the potential of CeO2 NPs to interfere with bacterial antioxidant defense systems, such as catalase and superoxide dismutase, thereby hindering the clearance of ROS and promoting its accumulation [19]. The elevated oxidative stress is expected to induce lipid peroxidation, which directly compromises the integrity of the bacterial cell membrane. While direct visual evidence from techniques such as transmission electron microscopy (TEM) for membrane disruption is beyond the scope of this study, the measured ROS surge strongly implies that membrane damage is a probable consequential event leading to increased permeability and eventual cell death [20]. In addition to its antibacterial role, CeO2 showed significant biocompatibility and even a stimulatory effect on DPSC proliferation. This finding is supported by Ren et al. [21], who found that periodontal ligament stem cells cultured with CeO2 NPs exhibited increased cell proliferation compared to cells cultured alone, possibly by enhancing cellular metabolic activity. Therefore, the above findings indicate the potential of CeO2 coating for inhibiting peri-implantitis and promoting DPSC proliferation.

The CeO2/BG-Ti implants markedly enhanced DPSC proliferation and osteogenic differentiation compared to Ti or BG-Ti controls. The reason maybe that the BG component can promote DPSCs adhesion [22], release osteogenic ions such as calcium and phosphate, and mimic the mineral composition of natural bone, which facilitate DPSC mineralization [24,25]. CeO2 NPs exhibit anti-inflammatory properties, which can create a more favorable microenvironment for DPSCs proliferation [23]. Notably, it has been reported that the controlled production of ROS by CeO2 NPs can act as signaling molecules to stimulate osteogenic differentiation in other stem cell types [26]. We hypothesize that a ROS-mediated pathway contributes to the upregulation of osteogenic markers (e.g., RUNX2, ALP, COL I) and enhanced mineralization observed in our experiments - a phenomenon also reported in bone marrow stromal cells by Li et al. [27]. However, the precise signaling mechanism requires further validation through ROS-scavenging or gene-knockdown approaches.

The in vivo results further confirmed the beneficial effects of the CeO2/BG coating. Implants coated with CeO2/BG exhibited the most markedly suppressed oxidative stress and inflammatory response. This suggests that CeO2 exerts antioxidant effects under physiologic conditions, likely due to its pH-dependent catalytic activity. In the physiologic pH of the healing peri-implant tissue, CeO2 acts as a potent antioxidant, scavenging excess ROS and thereby mitigating oxidative damage and subsequent inflammation. This role is crucial for creating a favorable microenvironment for bone regeneration [28]. Moreover, micro-CT consistently demonstrated superior bone healing and osseointegration around the CeO2/BG-Ti implants. The reason may be that BG has the ability to form a hydroxyapatite layer on its surface when in contact with bodily fluids, which mimics the mineral composition of natural bone, making it highly compatible with the surrounding bone [29,30]. Thus, the incorporated CeO2 plays a crucial dual role: it not only helps prevent bacterial colonization - a significant risk factor for peri-implantitis and implant failure [31] - but also, as previously discussed, mitigates local oxidative stress and inflammation Therefore, the combination of BG’s osteoconductivity and CeO2’s antibacterial/antioxidant properties synergistically facilitate better bone healing and exerts a more pronounced osteogenic effect.

Despite these promising results, our study has several limitations. First, evidence for CeO2-induced bacterial membrane damage remains indirect; future studies should include direct visualization via TEM. Second, we did not set up a separate CeO2-Ti group in animal experiments to better investigate its anti-inflammatory and antioxidant effects. Finally, the mechanistic role of CeO2 in promoting DPSC differentiation - particularly the involvement of ROS-related signaling pathways - was not directly verified through interventional experiments such as ROS scavenging or genetic knockdown. In a follow-up study, we need to further improve the above deficiencies to guide the later clinical trials.

Conclusion

CeO2 NPs can effectively inhibit P. gingivalis proliferation and have good biocompatibility with DPSCs. The combination of BG and CeO2 coating can more effectively promote the proliferation and mineralization of DPSCs, thus effectively improving the repair of peri-implant hard tissues. When CeO2/BG composite implants are placed in animal models, they effectively inhibit the degree of oxidative stress and the release of inflammatory factors, and exert osteogenic properties, providing a good microenvironment for the healing of the hard tissue around the implant. This creation of a conducive microenvironment for peri-implant healing may improve the long-term success of dental implants.

Disclosure of conflict of interest

None.

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