This study was conducted in accordance with the ethical standards of Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, and was approved by the Institutional Review Board (Approval No. 2026013-001). The extracted human teeth used in this study were collected from patients who underwent tooth extraction for orthodontic or periodontal reasons. Written informed consent was obtained from all participants before sample collection. No additional clinical intervention was performed for the purpose of this study. The study was conducted in accordance with institutional requirements for the use of extracted human teeth.
Specimen Preparation and Selection Criteria
A total of 141 single-rooted permanent teeth (mandibular incisors and premolars) that had been recently extracted were received from the Stomatology Dept., affiliated with Tongji University at Shanghai Fourth People’s Hospital. All teeth were removed due to orthodontic or periodontal reasons. Informed consent was obtained from each patient. Included in this study were teeth with roots of at least ten millimeters as determined by a periodontal probe, intact teeth with no carious lesions or cracks, complete root formation, and root curvature of less than ten degrees according to Schneider's method. Excluded from this study were teeth with multiple canals, canal calcification, internal resorption, or previous endodontic treatment. Following extraction, all visible calculus and soft tissue remnants were removed using a periodontal scaler. The teeth were then stored in 0.9% saline solution at 4°C until use to prevent dehydration, and all experiments were conducted within three months of extraction. The specimens were assigned to the experimental groups using a predefined alternating allocation sequence. Specifically, specimens were sequentially allocated to each group in an alternating manner until the required sample size for each group was reached. No formal a priori power calculation was performed. The sample size was selected based on previous comparable ex vivo studies, the number of irradiation parameter combinations evaluated, and the availability of eligible extracted teeth.
Root Canal Preparation and Sterilization
Each tooth crown was removed at the cementoenamel junction using a low-speed diamond saw under continuous water cooling to obtain a standardized 10 mm root segment. The working length was determined as 1 mm short of the apical foramen using a size 10 K-file. Root canals were prepared using the ProTaper Universal nickel–titanium rotary system according to the manufacturer’s instructions, following the sequence S1, S2, F1, F2, and F3 until an apical preparation size of F3 was achieved. During instrumentation, the canals were irrigated with approximately 2 mL of 5.25% sodium hypochlorite after the use of each rotary file, resulting in a total irrigation volume of approximately 10 mL per canal. A final rinse was performed with 5 mL of 17% EDTA for 1 min, followed by 5 mL of sterile saline. The apical foramen was sealed with flowable resin composite to create a closed canal system. Prepared roots were sterilized by autoclaving at 121°C for 20 min, stored in sterile phosphate-buffered saline (PBS) at 4°C, and inoculated with bacteria within 24 h after sterilization.
Bacterial Strain and Culture Conditions
E. faecalis ATCC 29212 was used to establish the infected root canal model. The strain was cultured on brain heart infusion (BHI) agar at 37°C for 24 h under aerobic conditions. A single colony was transferred to BHI broth and incubated at 37°C for 18–24 h. The bacterial suspension was adjusted to approximately 1.5 × 108 CFU/mL, equivalent to a 0.5 McFarland standard, using an optical density at 600 nm (OD600) value of 0.08–0.10.
Establishment of E. faecalis Infected Root Canal Model
To establish an infected root canal biofilm model, the external surface of each sterilized root was coated with two layers of clear nail polish to prevent bacterial penetration through the cementum. The apical region was coated after the apical foramen had been sealed with flowable resin composite, whereas the canal orifice was left uncoated to permit bacterial inoculation. Using a sterile micropipette, 10 µL of the E. faecalis suspension was transferred into each individual root canal to fill the entire length of the canal without spilling over. Inoculated samples were then individually placed in sterile 24-well culture plates, with 1.5 mL of BHI broth added to each well. Samples were cultured at 37°C under aerobic conditions for 21 days. The growth medium was removed and replaced with fresh sterile BHI broth every 2 days to provide nutrients for continued bacterial growth and to remove accumulated cellular debris. No additional inoculation with E. faecalis was performed during medium replacement. After completion of the incubation period, all viable samples were washed once with PBS to remove loosely attached planktonic bacteria before experimental testing. Two randomly selected samples were used to visualize mature biofilm formation and bacterial penetration into the dentinal tubules by scanning electron microscopy (SEM). The specimens were fixed in 2.5% glutaraldehyde at 4°C for 24 h, rinsed three times with PBS, dehydrated through a graded ethanol series (30%, 50%, 70%, 80%, 90%, and 100%), with each step lasting 10 min, then split longitudinally, air-dried, mounted on aluminum stubs, sputter-coated with gold, and examined by SEM.
Experimental Groups and Laser Irradiation Protocols
The 135 infected root samples were divided into three primary experimental groups according to the laser system used: the 808 nm Diode Laser Group, the 1940 nm Thulium Laser Group, and the 2940 nm Erbium Laser Group. There were 45 samples in each laser group, which were further subdivided according to the irradiation parameters. The diode laser was operated at average powers of 1.0, 1.5, or 2.0 W, and each power setting was applied for 10, 20, or 30 s, resulting in nine subgroups with three samples per subgroup. The thulium laser was operated at average powers of 1.5, 2.5, or 3.5 W, and each power setting was applied for 10, 20, or 30 s, also resulting in nine subgroups with three samples per subgroup. The erbium laser operated in a super-short pulse mode at a fixed frequency of 15 Hz. Pulse energies of 10, 20, or 30 mJ were applied for 10, 20, or 30 s, generating nine subgroups with three samples per subgroup. Both the 808 nm diode laser and the 1940 nm thulium laser were operated in continuous-wave mode.
In total, six additional samples were included, with three samples each assigned to the negative and positive control groups. The negative control group was treated with sterile saline, whereas the positive control group was treated with 5.25% sodium hypochlorite (NaOCl) for 30 s.
For the laser groups, a standardized irradiation protocol was followed. The optical fiber was introduced into the root canal to the working length and moved in a slow, continuous spiral motion from the apical to the coronal direction throughout the irradiation period. Laser-specific delivery fibers or tips were used rather than a single interchangeable fiber. The 808 nm diode laser was delivered through a 200 µm end-firing fiber, the 1940 nm thulium laser through a 200 µm end-firing fiber, and the 2940 nm erbium laser through a 400 µm radial-firing tip. The delivery fiber or tip was withdrawn at an approximate rate of 1 mm/s. After reaching the canal orifice, it was returned to the working length, and the apical-to-coronal spiral movement was repeated until the assigned irradiation duration was completed.
For the thulium and erbium lasers, the canals were kept filled with sterile saline during irradiation to simulate water-assisted laser activation. Approximately 10 µL of sterile saline was introduced into each canal to fill the canal to the level of the canal orifice before irradiation. The saline was replenished before each irradiation cycle, when necessary, to maintain a fluid-filled canal throughout treatment. For the diode laser group, the canals were dried with sterile paper points before irradiation because the 808 nm diode laser has relatively low absorption in water and was used to produce a direct photothermal antibacterial effect within the canal. By contrast, the 1940 nm thulium and 2940 nm erbium lasers have substantially greater water absorption and were therefore applied in saline-filled canals to facilitate water-mediated photothermal and photomechanical effects. The laser treatment was repeated once daily for three consecutive days.
Measurement of External Root Surface Temperature
Real-time temperature changes on the external root surface were measured during the first day of laser irradiation. Each root specimen was fixed vertically on a retort stand at room temperature (22°C ± 1°C). A K-type thermocouple connected to a digital thermometer was placed in firm contact with the mid-third of the external root surface, perpendicular to the long axis of the root. The thermocouple probe was positioned using an adjustable clamp and secured to the root surface with heat-resistant adhesive tape to maintain firm and consistent contact throughout the measurement. The thermocouple probe was calibrated before each measurement session using boiling water (100°C) and an ice–water mixture (0°C). Temperature readings were recorded at 50 ms intervals throughout the irradiation period (10, 20, or 30 s). Both the baseline temperature and the maximum temperature recorded during or immediately after laser irradiation were measured for each specimen. The temperature increase from baseline to peak temperature was calculated as ΔT. A ΔT exceeding 10°C was considered the threshold for potential damage to the periodontal tissues.
Microbiological Evaluation: Colony Counting and Inhibition Rate
To determine the antibacterial effect of the laser treatments, samples were collected after each laser treatment. The canal was dried with sterile paper points. A new sterile size 40 Hedström file was used for each specimen to obtain dentin chips from the canal walls, thereby preventing cross-contamination between samples. Each dentin chip was transferred into a separate microcentrifuge tube containing 1 mL of sterile PBS. The tubes were vortexed vigorously for 30 s to release bacteria from the dentin chips. Serial 10-fold dilutions ranging from 10−1 to 10−6 were prepared by transferring 100 µL of the bacterial suspension into 900 µL of sterile PBS at each dilution step. Aliquots (30 µL) of each dilution were spread onto separate brain heart infusion agar plates, which were incubated at 37°C for 24 h. Colonies were counted and recorded as colony-forming units (CFU). Each dilution was plated in triplicate, and the mean colony count from the three plates was used for analysis. The plates were coded before counting, and the investigator performing the colony counts was blinded to the treatment assignments.

Here, C is the mean CFU count of the negative control (saline) group and T is the mean CFU count of the experimental group.
Bacterial Growth Curve Analysis
The effect of various laser treatments on bacterial growth kinetics was investigated by plotting growth curves. On Day 3 after the final laser treatment, the canals were washed with 5 mL of sterile saline solution. The canal contents were collected using sterile paper points, which were then transferred into a centrifuge tube containing 5 mL of BHI broth. The tube was vortexed to suspend the bacteria in the broth. The bacterial suspension was adjusted to 1 × 106 CFU/mL. The bacterial concentration was adjusted based on OD600 measurements using a previously established calibration curve for E. faecalis ATCC 29212 and was subsequently verified by viable colony counting. An aliquot of 200 µL of the suspension was added to each well of a sterile 96-well microplate. In addition, 20 µL of sterile mineral oil was added to each well to minimize evaporation. The microplate was placed in a spectrophotometer/incubator maintained at 37°C, and OD600 was measured every hour for 24 h. Before each OD600 measurement, the microplate was subjected to orbital shaking at approximately 300 rpm for 10 s to ensure a homogeneous bacterial suspension. Each sample was tested in five replicate wells.
Statistical Analysis
All numerical data are presented as the mean ± standard deviation (SD). Statistical analyses were performed using SPSS Version 26.0. Data distribution was evaluated using the Shapiro–Wilk test. Analysis of variance (ANOVA) was used to compare more than two groups, followed by Tukey's honestly significant difference (HSD) test for pairwise comparisons. Comparisons between two groups were performed using an independent-samples t-test. Homogeneity of variance was assessed using Levene’s test before applying parametric tests. When the assumption of homogeneity of variance was violated, Welch’s correction was applied, as appropriate. Statistical significance was defined as P < 0.05. Graphs were generated using GraphPad Prism Version 9.0.