Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H₂O₂)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H₂O₂on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

Silver metal and compounds have antibacterial properties, although their action's mechanisms are not fully understood. Scientists generally consider that silver disrupts the bacterial cell wall. It causes a structural change in the bacterial cell membrane and cytoplasm. It also stops deoxyribonucleic acid replication, resulting in inactivating enzymatic activity and cell death. The antimicrobial effect of silver-containing compounds relies on the release of bioactive silver ions. Hence, silver metal and compounds have been used in medicine to prevent infection for hundreds of years. Silver metal and compounds are also used as antibacterial agents in dentistry. Studies have shown that silver compounds are effective in the management of dental caries. Fluoride-containing silver compounds have been found in experiments to be beneficial at remineralising dental cavities. Silver diamine fluoride (SDF) can assist in preventing and arresting tooth cavities. The World Health Organization included SDF in its Model List of Essential Medicine for both adults and children in 2021. Clinicians also use SDF to manage dentine hypersensitivity as well as to inhibit growth of periodontal pathogens. However, traditional silver compounds cause tooth discolouration because of the silver-staining effect. These side effects of their applications depend on the amount applied and the frequency of application. Researchers are developing nanosilver fluoride and silver nanoparticles to overcome the staining. This review gives an overview of the antibacterial mechanism of silver compounds, namely silver nitrate, silver fluoride, SDF, silver nanoparticles, and nano silver fluoride for caries management. The outlook for the future development of silver compounds will be discussed.

Silver nanoparticles have unique physical, chemical, and biological properties that make them attractive for medical applications. They have gained attention in dentistry for their potential use in caries management. This study reviews the different synthesis methods of silver nanoparticles and the application of them for caries management. Silver nanoparticles are tiny silver and are typically less than 100 nanometres in size. They have a high surface area-to-volume ratio, making them highly reactive and allowing them to interact with bacteria and other materials at the molecular level. Silver nanoparticles have low toxicity and biocompatibility. Researchers have employed various methods to synthesise silver nanoparticles, including chemical, physical, and biological methods. By controlling the process, silver nanoparticles have defined sizes, shapes, and surface properties for wide use. Silver nanoparticles exhibit strong antibacterial properties, capable of inhibiting a broad range of bacteria, including antibiotic-resistant strains. They inhibit the growth of cariogenic bacteria, such as Streptococcus mutans. They can disrupt bacterial cell membranes, interfere with enzyme activity, and inhibit bacterial replication. Silver nanoparticles can inhibit biofilm formation, reducing the risk of caries development. Additionally, nano silver fluoride prevents dental caries by promoting tooth remineralisation. They can interact with the tooth structure and enhance the deposition of hydroxyapatite, aiding in repairing early-stage carious lesions. Silver nanoparticles can also be incorporated into dental restorative materials such as composite resins and glass ionomer cements. The incorporation can enhance the material’s antibacterial properties, reducing the risk of secondary caries and improving the longevity of the restoration.

The status of reactive oxygen species (ROS) correlates closely with the normal development of the oral and maxillofacial tissues. Oxidative stress caused by ROS accumulation not only affects the development of enamel and dentin but also causes pathological changes in periodontal tissues (periodontal ligament and alveolar bone) that surround the root of the tooth. Although previous studies have shown that ROS accumulation plays a pathologic role in some oral and maxillofacial tissues, the effects of ROS on alveolar bone development remain unclear. In this study, we focused on mandibular alveolar bone development of mice deficient in superoxide dismutase1 (SOD1). Analyses were performed using microcomputerized tomography (micro‐CT), TRAP staining, immunohistochemical (IHC) staining, and enzyme‐linked immunosorbent assay (ELISA). We found for the first time that slightly higher ROS in mandibular alveolar bone of SOD1(‐/‐) mice at early ages (2‐4 months) caused a distinct enlargement in bone size and increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and expression of alkaline phosphatase (ALP), Runt‐related transcription factor 2 (Runx2), and osteopontin (OPN). With ROS accumulation to oxidative stress level, increased trabecular bone separation (Tb.Sp) and decreased expression of ALP, Runx2, and OPN were found in SOD1(‐/‐) mice at 6 months. Additionally, dosing with N‐acetylcysteine (NAC) effectively mitigated bone loss and normalized expression of ALP, Runx2, and OPN. These results indicate that redox imbalance caused by SOD1 deficiency has dual effects (promotion or inhibition) on mandibular alveolar bone development, which is closely related to the concentration of ROS and the stage of growth. We present a valuable model here for investigating the effects of ROS on mandibular alveolar bone formation and highlight important roles of ROS in regulating tissue development and pathological states, illustrating the complexity of the redox signal.

Reactive oxygen stress (ROS) is generally accepted as a signal transducer for coordinating the growth and differentiation of tissues and organs in the oral and maxillofacial region. Although ROS has been confirmed to affect the development of enamel, it is not yet known that the specific mechanism of ROS accumulation induced enamel defects. Given the lack of knowledge of the role of ROS in enamel, the aim of the study is to determine how oxidative stress affects cervical cells and ameloblast cells. Using SOD1 knockout mice, we identified a relationship between ROS fluctuations and abnormal enamel structure with HE staining, micro‐CT, and scanning electron microscope. Increased ROS induced by H₂O₂, certified by the DCFH probe, has resulted in a dual effect on the proliferation and differentiation of cervical cells, indicating a higher tendency to proliferate at low ROS concentrations. Ameloblasts transfected with SOD1 siRNA showed a significant reduction of RhoA and ROCK. This study investigates for the first time that SOD1‐mediated ROS accumulation disrupted normal enamel structure through alternative cervical loop cell proliferation and downregulation of RhoA and ROCK in ameloblasts, demonstrating the convoluted role of ROS in monitoring the progress of enamel defects.

The objective of this study is to develop a novel antibacterial and non-discolouring silver complex fluoride (SCF) for caries management. SCF was synthesized by reacting 1,3,5-triaza-7-phosphaadamantane (PTA) with silver fluoride and characterised by electrospray ionization mass spectrometry. Silver and fluoride concentrations were measured by inductively coupled plasma atomic emission spectroscopy and fluoride ion-specific electrode. Alkalinity was measured using a pH meter. Cytotoxicity was assessed by determining the half maximal inhibitory concentration (IC₅₀) against the human gingival fibroblasts (HGF-1) and stem cells from human exfoliated deciduous teeth (SHED). Demineralised human dentine blocks were treated with SCF, incubated for 7 days with Streptococcus mutans, and assessed for antibacterial activity and discolouration. Biofilm kinetics and viability were analysed via colony-forming unit (CFU) counts and confocal laser scanning microscopy (CLSM). Dentine discolouration was quantified using colour spectrophotometry. Controls included 38% silver diamine fluoride (SDF; positive) and water (negative). At 180 days, 55% SCF solution contained 127,498 ± 3,535 ppm silver and 27,215 ± 118 ppm fluoride, with a pH of 10. SCF demonstrated higher IC₅₀ values compared to SDF in HGF-1 (35.5 ± 1.1 ppm vs. 17.7 ± 0.5 ppm; p < 0.001) and SHED (95.5 ± 0.1 ppm vs. 6.4 ± 0.3 ppm; p < 0.001). Log CFU counts for the SCF, SDF, and Water groups were 4.2 ± 0.2, 3.8 ± 0.4 and 5.2 ± 0.2 (SCF, SDF<Water, p < 0.001). CLSM showed dead-to-live ratios of SCF, SDF and Water group were 1.0 ± 0.3, 1.4 ± 0.5, and 0.2 ± 0.1 (p < 0.001; SCF, SDF > Water). Spectrophotometric analysis revealed ΔE values of SCF, SDF and Water groups were 5.8 ± 3.3, 73.0 ± 17.6, and 5.3 ± 2.7 (p < 0.001; SCF, Water < SDF). A novel SCF solution with potent antibacterial efficacy and minimal discolouration was successfully developed. SCF demonstrates promising potential for clinical use in caries management, combining antimicrobial action with aesthetic preservation.