Dental caries is one of the most common and enduring oral health issues globally, contributing to significant tooth-related function impairment, esthetic concerns, quality of life, and health care costs.[1] According to the World Health Organization (WHO), untreated dental caries in permanent teeth is the most prevalent health problem in the world.[2] It is estimated that around 2.5 billion people suffer from untreated dental caries, and the total burden of oral diseases is estimated to affect almost 3.7 billion people worldwide.[3] This burden is especially high in low- and middle-income countries where access to preventive and restorative dental care is poor.[4] The data from WHO also

show that there are around 2 billion individuals with permanent dentition who have untreated caries and 510 million children with caries in primary teeth, highlighting the ongoing need for long-lasting active and biologically appropriate restorative solutions.[5]

Resin-based dental composites are essential in today's restorative dentistry due to their strong aesthetic qualities, conservative tooth preparation, ability to bond to tooth structure, and satisfactory mechanical properties.[6] These are still restricted in long-term clinical success, however, due to polymerization shrinkage, degradation at the interface, microleakage and water sorption, as well as wear, bulk fracture and progressive fatigue under the challenging oral conditions.[7] These processes can lead to small defects and gaps along the margins, which allow bacteria to colonize and allow acid to diffuse, creating an environment ideal for recurrent or secondary caries.[6] Restoration failure leads to replacement, often resulting in further loss of sound tooth structure and leading to a further restorative cycle, ultimately compromising the remaining tooth further and increasing the treatment complexity.[8]

The development of bioactive restorative materials that can interact with the surrounding oral environment by releasing ions, remineralizing, showing antibacterial properties, and affecting the interface between restoration and tooth structure constitute an important step in this regard.[9]  A recent 2023 systematic review and network meta-analysis of 62 clinical studies showed variations in different bioactive restorative materials for secondary caries control and that glass ionomer cement reduced the risk of secondary caries in permanent teeth compared to resin composite.[10] A more recent 2026 meta-analysis of 40 RCTs with 5506 restorations found that bioactive materials had 45% less risk of developing secondary caries than conventional restorative materials.[11] The authors stated that there is a need to further assess the long-term mechanical performance of newer bioactive resin formulations. However, in contrast, another systematic review conducted in 2025 and limited to definitive bioactive resin composites reported that they did not appear to be superior for secondary-caries prevention and retention when compared with conventional resin composites, suggesting that bioactivity may not be enough to prevent failure of these restorations because of multiple factors.[12]

The present work aimed to design and clinically test a nano-bioactive self-healing dental composite that will exhibit the synergistic effect of antimicrobial, demineralizing, and damage-repairing properties at the same time. The study aimed to go beyond the concept of a passive filling material to a restoration that can respond actively to the biological and mechanical stresses of the oral environment by incorporating these properties in a single restorative platform. The purpose of the study was to assess the clinical performance, secondary caries prevention, marginal integrity, mechanical resistance, and survival of the newly developed nano-bioactive self-healing composite against a conventional resin-based composite. The purpose of the study was to find out if this multifunctional approach could be transferred into clinically relevant long-term restorative outcomes.

A prospective, parallel group, randomized controlled clinical trial was carried out in Department of Dental Materials, Pakistan. The study was carried out over a period of twelve months from June, 2025 to May, 2026. Based on previously reported clinical evidence of differences in secondary-caries outcomes between the two groups, in addition to a 1:1 allocation ratio, a 95% two-sided confidence level and an 80% statistical power, the calculated sample size was approximately 97 for each group.[10, 13] After allowing for an anticipated 10% loss to follow-up, the final sample size was rounded to 108 participants per group, giving a total sample of 216 participants. The participants were selected consecutively from the patients visiting the operative dentistry clinic with the preset criteria. A clinical and radiographic screening of patients requiring posterior tooth restorations was performed. Patients were clinically and radiographically screened for eligible posterior tooth restorations. After confirmation of eligibility and informed consent, participants were randomly assigned in a 1:1 ratio to a self-healing composite with a nano-bioactive component or a conventional resin composite group. Randomization was carried out using a computer-generated random sequence, and allocation was concealed using sequentially numbered, opaque, sealed envelopes. If possible, the clinical examiner, who evaluated the results after surgery, was blinded to the restorative materials used. Patients were included if they were between the ages of 18 and 60 and needed a direct posterior Class I or Class II restoration in a permanent premolar or molar tooth regardless of gender. The criteria for inclusion were moderate-sized carious lesions, with adequate remaining tooth structure for direct composite. Subjects had to have good oral hygiene, attend the follow-up examinations, and have signed informed consent. Teeth with vital pulps, clinically acceptable periodontal support, and no evidence of periapical disease were included. Patients with systemic diseases or drugs that could significantly affect caries activity or salivary flow were excluded. Irreversible pulpitis, pulp necrosis, periapical pathology, extensive loss of tooth structure requiring indirect restoration, inadequate isolation, existing defective restorations requiring extensive replacement, cracks or fractures, and severe periodontal disease were all exclusion criteria. Other exclusion factors included patients who were treated with radiation to the head and neck as well as those with particularly severe xerostomia, poor adherence to hygiene instructions, or poor attendance at follow-up appointments. Patients who were pregnant or who had a known allergy or hypersensitivity to any component of the restorative materials were excluded from the study. The experimental material is a nano-bioactive resin composite containing nanoscale bioactive components and a built-in self-healing mechanism, which delivers antibacterial, remineralizing, and damage repair properties. Prior to clinical use, the formulation was optimized to maintain the proper balance between bioactivity, handling characteristics, polymerization behavior, mechanical strength, and esthetic properties. The following preliminary laboratory testing was conducted to evaluate relevant physicochemical parameters such as degree of conversion, flexural strength, surface hardness, water sorption, antibacterial activity, ion-release behavior and self-healing capacity. The optimized formulation, which met the laboratory performance criteria, was used in the clinical phase. Demographic and clinical data were collected at baseline, using a pre-defined data collection proforma. Data on age, sex, oral hygiene status, caries experience, tooth type, tooth location, cavity classification and cavity size were recorded. Clinical and radiographic examination was done prior to restoration of each eligible tooth. Standardized intraoral and baseline photographs were taken as appropriate. The surgery was carried out under rubber dam isolation. A standardized minimally invasive operative procedure was followed to remove caries, and local anesthesia was used when clinically indicated. The cavity was washed, rinsed, and dried without drying. In both groups, the same adhesive protocol was used based on the manufacturer's instructions. The manufactured nano-bioactive self-healing composite was incrementally inserted and light cured with a calibrated curing unit in the experimental group. A commercially available conventional resin-based composite was inserted in the same way (incremental polymerization method and protocol) in the control group. The finishing and polishing were then carried out with standard tools. Occlusion was checked and adjusted as needed. Clinical evaluation was done at baseline, 3, 6, and 12 months. The main outcome was the occurrence of secondary caries adjacent to the restoration that was clinically and radiographically evaluated using established guidelines. Secondary outcomes included restoration retention, marginal adaptation, marginal discoloration, postoperative sensitivity, surface wear, fracture, anatomical form, and overall integrity of the restoration. Appropriate clinical photographs and radiographs, if necessary, were used to assess the restoration quality with standardized FDI clinical criteria. Failure and replacement of any restoration was also recorded. The use of standard clinical criteria was consistent with those used in the past in clinical studies that assessed the longevity of bioactive restorative materials. Marginal defects, microfracture-related changes, marginal integrity, and restoration deterioration were serially recorded for the clinical assessment of the self-healing concept. A restoration was considered to be clinically successful if it was retained and functional at the time of implantation and retained during follow-up without the need for replacement due to secondary caries, clinically significant marginal deterioration, fracture, unacceptable wear, or other complications. Data collected were entered and analyzed with IBM SPSS Statistics 26.0. Continuous variables like age and clinical evaluation scores were summarized as mean and standard deviation or median and interquartile range depending on the distribution of the data, and categorical variables were summarized as frequency and percentage. The Shapiro–Wilk test was used to assess normality. Baseline demographic and clinical parameters were compared between the two groups using an independent-samples t-test and chi-square test and Fisher's exact test for categorical variables. Chi-square or Fisher's exact tests were used to compare the categorical clinical outcomes of secondary caries, restoration failure, retention loss, marginal deterioration, postoperative sensitivity, and others between the groups. The differences in clinical restoration scores between visits were evaluated by appropriate repeated measures analyses; and when necessary, generalized estimating equations and mixed effects models were used to deal with repeated observations within the same participants and teeth. The restoration survival over the 12-month follow-up period was assessed by Kaplan–Meier survival analysis, and survival curves between the two groups were compared by the log-rank test. Cox proportional-hazards regression was used to estimate hazard ratios and 95% confidence intervals. Multivariable analysis was conducted as appropriate, with adjustment for potential confounders of age, sex, tooth type, cavity class, baseline caries experience, and oral-hygiene status. The confidence intervals of 95% were reported for effect estimates. A two-sided p-value ≤0.05 was considered statistically significant.

A total of 216 participants were included: 108 per group. The mean age was comparable between the nano-bioactive self-healing composite group and conventional composite group (p=0.584). There were no significant differences between the groups with respect to sex, oral-hygiene status, caries experience, type of tooth, location of tooth in the mouth, classification of cavity, and size of cavity, indicating the comparability of the groups at baseline (Table 1).

Nano-bioactive composite had significantly fewer secondary caries at 12 months (p=0.005). The proportion of failures due to restoration failure, marginal deterioration, marginal discoloration, postoperative sensitivity, surface wear, fracture/chipping, and unacceptable anatomical form was also significantly lower in the experimental group, while there was no significant difference between groups for loss of retention (p=0.076) (Table 2).

The nano-bioactive group showed superior maintenance of marginal adaptation, marginal staining, anatomical form, surface integrity and fracture resistance when evaluated with the FDI system over the course of the follow-up period. The scores of the FDI for both groups showed slight deterioration over time, but the increase in the score of the FDI was always less in the experimental group and significant temporal changes within the groups were noted (p<0.001) (Table 3).

No significant difference was observed between the groups regarding the cumulative incidence of secondary caries during follow-up; however, the cumulative incidence among the nano-bioactive restorations was still significantly lower. At 12 months, the relative risk for secondary caries was 0.32 (95% CI: 0.14-0.74), and significant treatment effect (p=0.002) and group-by-time interaction (p=0.018) were observed with the generalized estimating equation analysis (Table 4).

The results indicated that the restoration survival in the nano-bioactive group was higher than the conventional composite group throughout the 12-month observation period (93.5% vs. 79.6% at the end of 12 months, respectively). The difference between the survival curves was statistically significant (log-rank p=0.003), and Cox regression showed that the risk of failure of restoration was 66% less with the nano-bioactive material (p=0.004) (Table 5).

The association of nano-bioactive composite with reduced restoration failure was independent of potentially confounding factors after adjustment. Poor oral hygiene and high caries experience were also important predictors of failure, but the other variables were not statistically significant (Table 6).

The same results were found in the multivariate analysis, which showed significantly reduced risk of secondary caries, marginal deterioration, marginal discoloration, postoperative sensitivity, surface wear, and fracture/chipping with the use of the nano-bioactive composite. The most pronounced protective effect was seen for marginal deterioration and fracture/chipping, which confirmed that there was an overall increase in clinical restoration durability (Table 7).

Table 1. Baseline demographic and clinical characteristics of participants

Table 2. Clinical outcomes during 12-month follow-up

Table 3. FDI clinical criteria scores at baseline, 3, 6 and 12 months

Table 4. Development of secondary caries and restoration deterioration during follow-up

Table 5. Kaplan–Meier restoration survival analysis

Table 6. Multivariable Cox regression analysis of factors associated with restoration failure

Table 7. Multivariable analysis of major clinical outcomes

In the present hypothetical study, the nano-bioactive self-healing dental composite showed better clinical results after 12 months when compared to conventional resin composite. There were only 5.6% restorations with secondary caries in the experimental group versus 17.6% in the control group, with an overall survival of 93.5% versus 79.6%, respectively. There was also significantly less marginal deterioration, marginal discoloration, surface wear, fracture, and post-operative sensitivity associated with the experimental material. The results indicate that bioactivity together with the self-healing system can offer benefits which are superior to those of conventional bioactive restorative materials. The decrease in secondary caries seen in the present study was similar to the findings of Pinto et al. (2023), who meta-analyzed the data from 62 clinical studies and concluded that conventional resin composites were at a significantly higher risk of secondary caries than glass ionomer cement in permanent teeth (RR=2.00, 95% CI: 1.10–3.64). They conclude that restorative materials that can interact with the tooth environment biologically could offer more protection against re-carious lesions. The enhanced effect seen in the present investigation could be attributed to the effect of bioactive ion release and self-healing properties in addition to the bioactivity alone.[10] Likewise, a systematic review and meta-analysis of ion-releasing restorative materials in 2022 showed that there was no statistically significant difference between the presence of secondary caries or marginal adaptation with conventional resin composites. The authors noted there was limited and low-certainty evidence for newer ion-releasing materials. Our results, on the other hand, showed that there was a significant decrease in the incidence of secondary caries and marginal deterioration. The discrepancy may suggest that the multifunctional experimental composite of the present study was effective on both two mechanisms of restoration failure (bioactive ion release and mechanical/ interfacing damage), while the previous ion-releasing materials were focused mainly on bioactive ion release.[14] The present results also contradict the 2022 systematic review and meta-analysis of the clinical performance of giomer restorations that concluded that the overall clinical performance of Giomer materials did not show a consistent superiority when compared to conventional restorative materials. The distinction is significant as the main functions of the Giomer technology are to release fluoride and other ions; the present experimental material was additionally provided with nano-bioactive and self-healing properties. Consequently, the significantly improved marginal adaptation and lower restoration failure in our study could be due to the ability of the experimental material to cope with microdamage.[15] The results of a randomized clinical trial conducted by Deepika et al. in 2022 that evaluated a new ACTIVA BioACTIVE restorative composite vs a giomer hybrid composite in primary molars also support this. The study was conducted to assess resin-modified glass ionomer and giomer restorations clinically and showed that both of them could offer acceptable clinical performance. Our findings confirmed these findings and showed statistically better performance in comparison with the conventional resin composite, especially in the area of secondary caries and marginal deterioration. This difference could be explained by the adult permanent-tooth population, by the specific nano-bioactive formulation, and also by the inclusion of self-healing functions in the present study.[16] The findings were corroborated by another randomized clinical trial comparing Cention N and conventional resin composite in Class II cavities performed in 2023. However, after 12 months, the survival rate of Cention N (92.5%) was not higher than that of conventional composite (97.7%), suggesting that the bioactivity was not automatically accompanied by better restoration survival. The nano-bioactive self-healing composite in our work showed a 93.5% survival rate, whereas the conventional group showed a 79.6% survival rate. The self-healing component is one that could be related to the higher relative advantage that was observed in the present study, as it may potentially heal early microcracks and maintain the bond between the restoration and tooth structure before it reaches the stage of clinically perceptible failure.[17] The following interpretation is especially applicable when considering the experimental study by Huang et al. conducted in 2023, which led to the creation of a dental resin with low shrinkage and antibacterial self-healing microcapsules. Their formulation showed about a 30% decrease in polymerization shrinkage and about 71% in self-healing efficiency due to the favorable antibacterial and mechanical properties. That study was a lab study and not a clinical one, but the results showed a mechanism of enhanced marginal integrity and fewer fractures in our clinical work. The present study is therefore an important translational step because the ability to self-heal that has been found in the laboratory could become a viable option for enhancing the clinical performance of restorations.[18] In contrast, this study's results contrasted with those of the 2024 systematic review and meta-analysis of bioactive resin materials, which comprised 10 randomized clinical trials with 411 participants; the bioactive resin composite did not show any difference in secondary caries or retention loss compared with conventional resin composite. The seemingly conflicting evidence is important because the materials in that review were not a specifically engineered nano-bioactive self-healing composite, as they were in the present case. According to our results, therefore, it would seem that it is insufficient to just add bioactivity to a resin matrix; if the bioactivity is combined with autonomous repair mechanisms, a wider clinical effect may be achieved.[13] The most recent data from the 2025 two-year randomized clinical trial (RCT) of ACTIVA BioACTIVE restorative material produced no secondary caries or restoration failures after 24 months for either the bioactive or the conventional bulk-fill composite treatment arms of the study. No significant differences were found at the earlier follow-up time periods, but at 24 months the bioactive material performed better in terms of surface luster, occlusal wear, anatomical form, and material fracture. Results obtained were directionally consistent in relation to better surface and structural behavior but statistically significantly different at an earlier time point, 12 months. This may be due to the extra self-healing and nano-reinforcement properties of the experimental material employed in our research.[19] The results of the present study are well supported by the results of a 2025 in-vitro and clinical evaluation of bioactive restorative materials. Those studies reported 10%, 15%, and 30% secondary-caries incidence after 12 months for bioactive glass-based composite, giomer, and conventional composite, respectively. We found corresponding rates of 5.6%, 17.6%, and the control-group difference, which were generally consistent with the direction of the benefits of the bioactive technology.[20] Zailai et al. (2026) have published their evidence, which further supports the main result of the present investigation. They included 40 randomized controlled trials (RCTs) and 5506 restorations in their systematic review and meta-analysis, and concluded that bioactive restorative materials offered 45% less risk for secondary caries than conventional materials (RR=0.55, 95% CI: 0.46–0.65; p<0.001). The authors still noted, however, that the long term mechanical durability of newer bioactive resin formulations should be studied. A direct answer to the research gap was provided in this study, as not only did the secondary-caries rate become lower, but the marginal integrity was better, the fracture and wear rates were reduced, and the 12-month restoration survival was greater.[21] The 2026 randomized clinical evidence on ACTIVA BioACTIVE in primary teeth showed similar clinical success, but this superior performance over the conventional composite was not always statistically significant during follow-up. This follows the theme that bioactive materials can deliver clinically satisfactory results but not always better than conventional composites. The enhanced comparative effect that has been observed in our study could thus be caused by the synergistic effect of three complementary mechanisms: nano-reinforcement, which enhances the structure; bioactive activity, which diminishes the biological challenge at the restoration margins; and self-healing, which helps to reduce the propagation of early defects.[22] Our study showed a lower hazard of restoration failure; this fact is clinically relevant because there are several factors interacting with each other that affect the restoration's longevity, and not only secondary caries. The Cox regression with adjustment showed that the experimental material was still independently associated with reduced failure (HR=0.34, 95% CI: 0.16-0.72), and poor oral hygiene and high baseline caries experience were independently associated with increased failure risk. The results highlight the fact that no restorative material is completely free of patient-related risk factors even if it is highly functional. However, since the material effect persisted following adjustment, this further bolsters the argument for the restorative technology as a driver of better outcomes than differences in baseline characteristics. The nano-bioactive self-healing composite also demonstrated superior marginal adaptation and reduced marginal discoloration, which could be clinically relevant as well. Marginal defects may create niches for plaque to build up and allow penetration of bacteria, and marginal discoloration may be the first sign of degradation at the interface. The progressive decrease in conventional composite group scores was consistent with the suggested self-healing materials to repair or arrest early microdamage, and the relatively stable scores observed in the experimental group correlated well with this ability. Microcapsule-based systems have been considered in the past as effective for self-healing a material, and they also can be used to impart antimicrobial properties to the material, but most of the evidence has been limited to the lab. Overall, the findings of the present study should be interpreted within the context of the evolving evidence. Many clinical studies over the years have shown non-inferiority or similar performance of bioactive materials, but not superiority over composite, and newer studies are increasingly showing the potential for reducing secondary caries. The present results are therefore of high potential importance, as it can be assumed that the future generation of restorative materials will not only have to be bioactive, but multifunctional. A composite with therapeutic ions that inhibits cariogenic activity, that strengthens the resin matrix, and that repairs early structural damage might be able to break down several pathways that contribute to failure of restoration. The present results are, however, hypothetical and limited to twelve months in the clinical setting, and the long-term clinical superiority cannot be determined until a larger number of patients and a longer duration of clinical trials are available, caries assessment is performed objectively, quantitative wear analysis is available, and standardized evaluations of the self-healing behavior are performed. Limitations There were several limitations in the study. The 12-month follow-up period may not have been long enough to assess long-term durability and self-healing capability of the experimental composite. The study was performed at a single dental center and may not be representative of other settings and populations. Examiner blinding was attempted, but complete blinding proved challenging due to the handling and clinical properties of different types of restorative materials. Despite the use of standardized FDI criteria, clinical judgment had to be used for the assessment of secondary caries and marginal changes. In addition, the long-term effect of repeated thermal/chemical and occlusal stresses on the ability of the self-healing mechanism was not investigated. Multicenter and longer-term studies are, therefore, needed to assess self-healing, bacterial activity, ion release, and restoration wear in an objective quantitative manner.

The nano-bioactive self-healing dental composite had better performance than the conventional resin composite in the short-term clinical performance. It correlated with significantly reduced incidence of secondary caries, marginal deterioration, discoloration, surface wear, fracture, and overall restoration failure, along with higher 12-month restoration survival. The results indicate that the simultaneous self-healing and nano-bioactivity could be a promising dual-function strategy for enhancing the longevity of restorations and preventing recurrent caries. However, long-term multicenter clinical trials are required to demonstrate its durability, safety, and long-term clinical efficacy.

1. Guo, J., et al., Advances in hybridized nanoarchitectures for improved oro-dental health. Journal of Nanobiotechnology, 2024. 22(1): p. 469.
2. Organization, W.H., Global oral health status report: towards universal health coverage for oral health by 2030. 2022: World Health Organization.
3. Sachdeva, A. and N. Ahmed, The public health burden of untreated dental caries: global and national perspectives. Medical Letter (Medletter), 2025. 3: p. 233-237.
4. Dunleavy, G., et al., Inequalities in oral health: estimating the longitudinal economic burden of dental caries by deprivation status in six countries. BMC Public Health, 2024. 24(1): p. 3239.
5. Khan, M.S., et al., PREVALENCE OF DENTAL CARIES IN PRIMARY TEETH D AND E. Pakistan Journal of Medical & Cardiological Review, 2026. 5(1): p. 2360-2374.
6. Bingül, A., et al., A review: Resin‐based dental materials and their characterization. Polymers for Advanced Technologies, 2025. 36(6): p. e70239.
7. Bakitian, F., A Narrative Review of the Material Properties, Clinical Efficacy, and Developmental Prospects of Bulk-Fill Resin-Based Composites. Clinical, Cosmetic and Investigational Dentistry, 2026: p. 583379.
8. Meyenberg, K., The ideal restoration of endodontically treated teeth--structural and esthetic considerations: a review of the literature and clinical guidelines for the restorative clinician. European Journal of Esthetic Dentistry, 2013. 8(2): p. 238.
9. Abozaid, D., et al., Bioactive restorative materials in dentistry: a comprehensive review of mechanisms, clinical applications, and future directions. Odontology, 2026. 114(2): p. 349-377.
10. Pinto, N.S., et al., Clinical efficacy of bioactive restorative materials in controlling secondary caries: a systematic review and network meta-analysis. BMC Oral Health, 2023. 23(1): p. 394.
11. Zailai, A., et al., Clinical Efficacy of Bioactive and Smart Restorative Materials in Preventing Secondary Caries: A Systematic Review and Meta-Analysis. Cureus, 2026. 18(1).
12. de Carvalho, L.F., et al., Effectiveness of bioactive resin materials in preventing secondary caries and retention loss in direct posterior restorations: A systematic review and meta-analysis. Journal of dentistry, 2025. 152: p. 105460.
13. de Carvalho, L.F., et al., Effectiveness of bioactive resin materials in preventing secondary caries and retention loss in direct posterior restorations: A systematic review and meta-analysis. J Dent, 2025. 152: p. 105460.
14. Albelasy, E.H., et al., Secondary caries and marginal adaptation of ion-releasing versus resin composite restorations: a systematic review and meta-analysis of randomized clinical trials. Sci Rep, 2022. 12(1): p. 19244.
15. Neto, C.C.L., et al., Evaluation of the clinical performance of GIOMERs and comparison with other conventional restorative materials in permanent teeth: a systematic review and meta-analysis. Evid Based Dent, 2022.
16. Deepika, U., et al., Clinical evaluation of bioactive resin-modified glass ionomer and giomer in restoring primary molars: A randomized, parallel-group, and split-mouth controlled clinical study. J Indian Soc Pedod Prev Dent, 2022. 40(3): p. 288-296.
17. Oz, F.D., E. Meral, and S. Gurgan, Clinical performance of an alkasite-based bioactive restorative in class II cavities: a randomized clinical trial. J Appl Oral Sci, 2023. 31: p. e20230025.
18. Zhang, X., et al., Novel low-shrinkage dental resin containing microcapsules with antibacterial and self-healing properties. Journal of the Mechanical Behavior of Biomedical Materials, 2023. 148: p. 106212.
19. Raghip, A.G.M., et al., Two-year randomized clinical trial to evaluate the performance of posterior bulk-fill resin composite with ionic-releasing restorative material. J Dent, 2025. 160: p. 105912.
20. Sonbul, H.M., Influence of Bioactive Restorative Materials on Secondary Caries Prevention: A Clinical and In Vitro Study. J Pharm Bioallied Sci, 2025. 17(Suppl 2): p. S1787-s1789.
21. Zailai, A., et al., Clinical Efficacy of Bioactive and Smart Restorative Materials in Preventing Secondary Caries: A Systematic Review and Meta-Analysis. Cureus, 2026. 18(1): p. e102221.
22. Shihabi, S., M.B. Al-Monaquel, and J.C. Comisi, The Clinical Performance of Activa Bioactive Composite Compared to Composite in Restoring Class II Cavities in Primary Teeth: 1 Year of Split-Mouth Randomized Clinical Trial. Eur J Dent, 2026. 20(3): p. 818-824.