The primary goals of orthodontic treatment are to improve the occlusion and profile of patients with malocclusion, and fixed orthodontic therapy is the most recommended due to its superior control of tooth movement [1]. However, fixed orthodontic appliances and excessive adhesives create an ideal environment for bacterial adhesion sites, leading to carbohydrate fermentation by these microbe and subsequent organic acid production [2,3]. The accumulation of these acids on the enamel surface leads to a reduction in pH levels, ultimately causing enamel demineralization surrounding and beneath orthodontic brackets [4]. The enamel demineralization are the primary complications associated with fixed orthodontic therapy and recognized as a major risk factor [5]. Prevalence of enamel demineralization following fixed orthodontic treatment have been reported to range from 73% to 95% among patients, with an incidence rate of at least one white spot lesion ranging from 36% to 46% [6,7]. Effective oral hygiene management is the basis of preventing enamel demineralization during orthodontic therapy, while the patient compliance may not always reliable, particularly among children and adolescents [8,9]. Therefore, incorporating bioactive materials into adhesives represents a promising strategy for preventing and treating enamel demineralization during orthodontic treatment.

Various compositions, such as antibacterial agent, quaternary ammonium resin monomer, and nano-silver, have been implemented to impart orthodontic adhesives with antibacterial activity [10], [11], [12]. Amongst these additives, arginine, a basic amino acid, received much attention. Arginine is recognized as a prebiotic-based biofilm modifier that can be hydrolyzed by acidogenic microorganisms through the arginine deiminase (ADS) pathway, resulting in ammonia production. This process increases the biofilm pH value, suppresses harmful aciduric species, and inhibits the growth of bacteria [13,14]. Extensive clinical cohorts and studies of saliva-derived biofilm model have reported that arginine treatment could promote the ecological balance in oral microbiota by enriching alkali-producing bacteria while inhibiting acid-producing pathogenic species [15,16]. Accumulating in vivo data have demonstrated that oral hygiene products containing arginine exhibit a significant reduction in the incidence of dental caries [17]. The drawback of the free addition of arginine into adhesives is the short duration of the antibacterial effect due to the limited release periods, as well as the potential impairment of material integrity [18]. Therefore, developing a reasonable arginine delivery system could serve as an ideal strategy to address this issue.

Mesoporous silica nanoparticles (MSNs) are considered ideal nanocarriers for drug encapsulation and release due to their large surface area and pore volume, stable framework, and easy surface functionalization [19,20]. In recent years, MSNs have been widely applied in dental materials modification as antibacterial active ingredients reservoirs. For instance, Yan et al. demonstrated that MSNs could effectively encapsulate chlorhexidine and applied in modified glass ionomer cements, resulting in antibacterial activity without compromising mechanical performance [21]. Above all, MSNs could be ideal nanocarriers to encapsulate and release arginine and the incorporation of arginine loaded MSNs (Arg@MSNs) to orthodontic adhesive would be effective in enhancing its antibacterial performance and ultimately combating enamel demineralization.

Accordingly, the objective of this study was to synthesize Arg@MSNs and investigate their application as multifunctional fillers for modifying orthodontic adhesive in terms of its adhesive performance, antibacterial activity and biocompatibility. The null hypothesis tested was that the inclusion of Arg@MSNs in orthodontic adhesive would not yield significant differences in the degree of conversion, adhesive performance, antibacterial activity, and biocompatibility compared to commercial orthodontic adhesives.