Submitted:
23 December 2025
Posted:
25 December 2025
You are already at the latest version
Abstract
Endodontics is undergoing a paradigm shift from conventional root canal therapy toward regenerative and technologically integrated solutions. Persistent biofilms, structural fragility, and loss of vitality after treatment remain major clinical challenges, driving the need for novel strategies. This review provides a comprehensive overview of transformative technologies that are redefining the field, including nanotechnology, microrobotics, 3D printing, artificial intelligence (AI), and environmentally stimuli-responsive biomaterials. Nanotechnology introduces nanoparticles and nanozymes with potent antimicrobial, remineralizing, and regenerative properties, while microrobotic systems offer unprecedented precision in intraradicular navigation, biofilm disruption, and targeted drug delivery. Three-dimensional (3D) printing enables the fabrication of patient-specific scaffolds, canal replicas for training and evaluation, and bioengineered pulp–dentin complexes. Stimuli-responsive hydrogels and smart biomaterials add another dimension by providing controlled, site-specific therapeutic release in response to pH, temperature, redox state, or enzymatic cues. Artificial intelligence further enhances diagnostic accuracy, imaging interpretation, treatment planning, and outcome prediction, and when combined with 3D models, enables the concept of digital twins for personalized endodontic care. Collectively, these advances are converging toward a vision of regenerative and precision endodontics that is minimally invasive, biologically integrative, and sustainable. By synthesizing current progress and future directions, this review outlines a translational roadmap that positions next-generation endodontics within the broader landscape of advanced healthcare materials at the interface of biology, engineering, and digital technology.
Keywords:
1. Introduction: Toward Next-Generation Endodontics
2. Artificial Intelligence in Endodontics
3. Microrobotics for Intraradicular Therapy
3.1. Anatomical Targets and Navigation Advances
3.2. Architecture and Actuation Strategies
3.3. Imaging, Sensing, and Closed-Loop Control
3.4. Therapeutic Mechanisms and Anti-Biofilm Strategies
3.5. Targeted Drug Delivery and Regenerative Potential
3.6. Regenerative Micro-Interventions
3.7. Synergy with Current Endodontic Instrumentation and Irrigation
3.8. Materials, Biocompatibility, and Safety Considerations
3.9. Materials, Biocompatibility, Safety, and Limitations
3.10. Evaluation Framework, Models, Metrics, and Reporting Standards
3.11. Clinical Translation and Future Directions
3.11. Clinical Translation, Regulation, and Future Directions
3.12. Regulatory, Ethical, and Economic Considerations with a Focused Research Roadmap
4. 3D Printing & Bioprinting
| Ref | Title | Conclusion |
|---|---|---|
| [97] | Guided Endodontics: Volume of Dental Tissue Removed by Guided Access Cavity Preparation-An Ex Vivo Study | Guided endodontic access GEA preserved a greater volume of dental tissue in extracted upper human molars than conventional endodontic access CEA; however, there was no significant difference between CEA and GEA in the volume of dental tissue removed from mandibular incisors. |
| [98] | Guided Endodontics for a Tooth with Root Fracture: A Case Report | The obtained results suggest that the use of guided endodontics can improve outcomes in cases with pulp canal obliteration and complex fractures, offering a minimally invasive and predictable approach. |
| [99] | Targeted Endodontic Microsurgery of a Mandibular First Molar with a Separated Instrument Using the 3D-printed Guide and Trephine Bur: A Case Report with a 2-year Follow-up | This case report describes the use of the 3D-printed guide and the trephine bur to accurately perform Endodontic microsurgery of a mandibular first molar with a separated instrument and periapical lesions. |
| [100] | Effective Management of Calcified Root Canals Using Static-guided Access: A Case Series | The cases demonstrated that static-guided endodontics is a safe accurate treatment approach to access calcified canals, reducing working time, minimizing removal of tooth structure, and decreasing the risk of iatrogenic damage. |
| [101] | Guided endodontics a pathbreaking approach to the management of calcified canals: A case report | For conservative, precise, and predictable outcomes, a digital workflow that makes use of CBCT imaging, planning software, and a 3D-printed endodontic guide may be taken into consideration when managing extensively calcified canals. |
| [102] | Minimization of Tooth Substance Removal in Normally Calcified Teeth Using Guided Endodontics: An In Vitro Pilot Study | The use of guided endodontics in normally calcified teeth enables the preservation of a significant amount of tooth substance. However, this advantage must be carefully balanced against a greater radiation burden and risk of perforation, higher costs, and more difficult debridement and visualization of the pulp chamber and root canals. |
| [103] | Real-Time Guided Endodontics with a Miniaturized Dynamic Navigation System Versus Conventional Freehand Endodontic Access Cavity Preparation: Substance Loss and Procedure Time | real-time guided endodontics is a practicable, substance-sparing method performed in comparable time as the conventional freehand method. Moreover, real-time guided endodontics seems to be independent of operator experience. |
| [95] | Case Report: Dental autotransplantation for the resolution of odontogenic sinusitis using 3D replication | This case demonstrates that, when properly planned and executed, dental autotransplantation can be an effective and biological alternative for dental rehabilitation, especially with the use of advanced technologies, such as cone beam computed tomography and 3D-printed replicas of donor teeth. |
| [104] | Guided endodontics versus conventional access cavity preparation: an ex vivo comparative study of substance loss |
For access cavity preparation in teeth with pulp canal calcification, both conventional access cavity preparation by a specialist and guided endodontics by a general dentist produce good results in terms of substance loss and time requirements. |
| [87] | Influence of Calcified Canals Localization on the Accuracy of Guided Endodontic Therapy: A Case Series Study | In any of the analyzed cases, the guided endodontic technique applied to pulp canal obliteration did not determine the presence of iatrogenic errors, such as perforations. However, the apical localization of the obliteration increases the probability of being off-center with the drill during the instrumentation phase by about 15 times. |
| [105] | Comparing accuracy in guided endodontics: dynamic real-time navigation, static guides, and manual approaches for access cavity preparation - an in vitro study using 3D printed teeth | Although guided endodontic access preparation may require more time compared to the freehand technique, the guided navigation is more accurate and saves tooth structure. |
5. Regenerative Endodontic
5.1. Strategies in Regenerative Endodontics
5.2. Cell Transplantation Strategy
5.3. Cell Homing Strategy
5.4. Stem/Progenitor Cell Sources
5.5. Scaffolds in Regenerative Endodontics
5.6. Natural Scaffolds
5.7. Synthetic Polymer Scaffolds
5.8. Bioceramic and Composite Scaffolds
5.9. Smart and Advanced Scaffolds
5.10. Clinical Trials
5.11. Challenges and Limitations
5.12. Future Perspectives
6. Imaging in Endodontic Practice
6.1. Cone-Beam Computed Tomography (CBCT)
6.2. Micro-Computed Tomography (micro-CT)
6.3. Ultrasound
7. Conclusion and Future Perspectives
Author Contributions
Data Availability Statement
Acknowledgments
Conflicts of Interest
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| AI Application | Studies |
|---|---|
| Analysis of Tooth, Root, And Canal Morphology | [14,15], [16,17,18,19,20,21] |
| Patient Understanding and Anxiety in Endodontics | [22] |
| Root Canal Orifice Identification | [23] |
| Diagnosis, Treatment Planning, And Clinical Decision-Making | [7,9,24], |
| Caries And Periapical Periodontitis Detection | [8,25], |
| Study (Ref) | Type of Microrobotics Used | Aim of the Study | Significance |
|---|---|---|---|
| Dasgupta et al., 2022 [29] | Magnetic helical silica–iron nanorobots | Intratubular navigation and localized hyperthermia against E. faecalis | Achieved ~2 mm intratubular navigation and localized hyperthermia for E. faecalis disinfection. |
| Hwang et al., 2019 [60] | Catalytic magnetic microrobot swarms | Mechanochemical biofilm eradication on dental substrates | Enabled mechanochemical biofilm eradication and tetherless intracanal disinfection with radiographic tracking. |
| Babeer et al., 2022 [66] | Iron-oxide-nanoparticle-based catalytic magnetic microswarms and opacifier-infused 3D-molded soft helicoids | Tetherless intracanal biofilm disruption and sample retrieval with controlled magnetic navigation to the apical region, plus radiographic tracking using opacifier-infused helicoids. | Magnetically responsive nanozyme capsules and adaptive assemblies provided targeted, selective biofilm disruption in confined spaces. |
| [48]Tran et al., 2025 | Magnetically responsive nanozyme-shelled microcapsules | Target and disrupt biofilms in confined microgeometries | Provided boundary-following contact and rapid, selective biofilm treatment in narrow channels and confined spaces. |
| [47] Tran et al., 2025 | Adaptive robotic microcapsule assemblies | Treat biofilms in rugged, crevice-rich spaces | Adapted mobility for sustained contact-catalytic disruption in tortuous, crevice-rich anatomy. |
| Mayorga-Martinez et al., 2022 [64] | Swarming photoactive magnetic microrobots | Eradicate biofilm on complex dental surfaces | Showed mechanochemical synergy of scrubbing with photoactivation on implant substrates, with potential translation to intraradicular biofilms. |
| Sun et al., 2025 [59] | Liquid-bodied magnetic soft robots | Navigate and clear biofilms on undulating, trench-like surfaces | Overcame complex surface topographies using switchable viscoelastic properties and achieved effective antibiofilm performance on rugged surfaces. |
| Mayorga-Martinez et al., 2023 [65] | Multimodal magnetic microrobots | Debride biofilms in crevices and meshes | Validated access and debridement in crevice-like features and titanium meshes, analogous to root-canal recesses. |
| Xing et al., 2025 [34] | 3D-printed microrobots integrating magnetic actuation, MPI visibility, and magnetothermal therapy | Combine navigation, imaging, and localized therapy | Platform integrates actuation, magnetic particle imaging visibility, and magnetothermal treatment, aligning with image-guided interventions in constrained anatomy. |
| [49] Gao et al., 2024 | Soft helical magnetic microrobots | Targeted antimicrobial or drug delivery | Demonstrated drug-carrying helical soft microrobots where geometry controls swimming and torque, enabling guided delivery. |
| Ye et al., 2023 [52] | Ligand-targeted magnetic microrobots | Bind receptor-positive targets for specific payload delivery | Added molecular specificity via folate targeting to enhance guided disinfection or therapy in heterogeneous infections. |
| Li et al., 2019 [36] | Magnetically actuated microrobots with optical coherence tomography (OCT) feedback | Closed-loop imaging guidance for navigation | Provided high-resolution OCT feedback for closed-loop navigation and tracking in shallow tissues, useful near the chamber and orifice. |
| Alabay et al., 2024 [37] | Miniature magnetic robots localized by clinical C-arm fluoroscopy | Radiographic localization and steering | Demonstrated real-time localization and steering of miniature robots using clinical C-arm fluoroscopy with VR interface, compatible with procedural settings. |
| Li et al., 2024 [38] | Magnetic microrobots in clinical-scale fields | Demonstrate human-scale magnetic navigation | Supported feasibility of clinical magnetic navigation systems at human scale, informing translation to dental settings. |
| Go et al., 2022 [39] | MRI-visible, magnetically driven PLGA-gelatin microbeads with surface Fe3O4 | Combine vessel embolization and doxorubicin delivery with intra-operative real-time x-ray guidance and postoperative MRI confirmation | Demonstrated magnetic targeting and selective embolization in a rat liver tumor model with drug-loaded beads, real-time x-ray tracking during targeting, and postoperative MRI localization. Provides a complete imaging-actuation-therapy workflow that informs translational imaging stacks for constrained anatomies. |
| Signaling Molecules | Role | Ref |
|---|---|---|
| SDF-1 | central regulator that drives mesenchymal stem cell (MSC) mobilization through its receptor CXCR4 | [126,127,128]. |
| PDGF |
Platelet derived growth factor is equally vital, supporting both angiogenesis and mesenchymal stem cells (MSC) recruitment processes indispensable for pulp dentin complex regeneration | [125,129]. |
| FGF | Fibroblast growth factor (FGF) contributes by enhancing cell migration and differentiation, thereby accelerating reparative events | [125,130,131]. |
| TGF-β | transforming growth factor beta regulates cell movement and stimulates odontoblastic differentiation, playing a pivotal role in orchestrating tissue regeneration | [125,132,133]. |
| Stem cells | Role | Ref |
|---|---|---|
| SCAPs | Stem cells from apical papilla exhibit high proliferative potential and resistance to inflammation, rendering them particularly advantageous for pulp dentin regeneration. | [125,134]. |
| iPAPCs | Inflammatory periapical progenitor cells identified in inflamed periapical lesions, display differentiation, making them important contributors to reparative pathways. | [135]. |
| BMMSCs | Bone marrow-derived mesenchymal stem cells are adaptable to diverse environments and support both bone and pulp repair. |
[136,137]. |
| PDLSCs | periodontal ligament stem cells possess immunomodulatory activity alongside odontogenic potential. | [138,139,140]. |
| Biomaterial | Significance | Limitations | Scaffolds Used | References |
|---|---|---|---|---|
| Collagen | Highly biocompatible and bioactive; key component of pulp–dentin ECM; supports mineralization and differentiation. | Pure collagen lacks mechanical strength and regenerative capacity without additives. | Collagen–hydroxyapatite composites, collagen–hyaluronic acid, and AceCol scaffolds. | [7,35,36,37] |
| Alginate | Biocompatible, low immunogenicity, and versatile in scaffold formation. | Weak mechanics and uncontrolled biodegradation. | Alginate/acemannan beads, PVA/alginate composites, and silk fibroin–alginate hydrogels. |
[38,39] [40] |
| Hyaluronic acid | Excellent biocompatibility, supports cell environment, non-cytotoxic. | Limited adhesion, proliferation, and differentiation enhancement. | Photocross-linked silk fibroin/HA hydrogels with hDPSCs. | [25,41] |
| Cellulose | Abundant, cost-effective, supports adhesion and odontogenic differentiation. | Weak mechanical strength and low intrinsic bioactivity. | Carboxymethyl cellulose–Laponite nanocomposite hydrogels. | [41] |
| Chitosan | Antibacterial, bioactive, supports pulp-like tissue formation, versatile for drug delivery. | Poor mechanical strength; properties vary by source/deacetylation. | Chitosan–gelatin–alginate, calcium silicate–chitosan, and phosphorylated pullulan–chitosan scaffolds. | [42,43], [20] |
| Decellularized ECM (dECM) | Preserves ECM proteins, enhances cell proliferation, supports vital pulp regeneration. |
Preparation is complex and variable. | dECM–silk fibroin hybrids |
[44,45] |
| Fibrin | Injectable, biocompatible, reduces infection, supports pulp regeneration. | Mechanical strength and degradation rate depend on scaffold design. | Dentin ECM–bioactive glass/GelMA and fibrin-based hydrogels. | [15,41,45] |
| Gelatin | Derived from collagen, biocompatible, low immunogenicity, supports controlled release of growth factors. | Rapid degradation and weak mechanical properties unless reinforced. | Gelatin–chitosan–alginate scaffolds. | [14,39] |
| Silk | Robust, stable under environmental stress, highly compatible with stem cells. | Requires precise degumming to remove immunogenic sericin. | Silk fibroin/HA hydrogels and silk–hydroxyapatite composites. | [16] [46] [47] |
| Host-derived scaffolds | Autologous, immune-safe, rich in growth factors, promotes stem cell recruitment. | Variable effectiveness and lack of preparation standardization. |
Platelet-rich plasma scaffolds. | [26] [1] [52] |
| Type of stimuli | Advantages | Limitations | References | |
|---|---|---|---|---|
| Physical Stimuli | Light Responsive Hydrogel | Offer precise spatiotemporal control (e.g., stiffness modulation, drug release) and rapid responsiveness (≈260 ms). NIR light allows deep tissue penetration (e.g., inside root canals). |
Risk of cytotoxic byproducts and unintended heat damage. | [30] [13] [31] |
| Thermo-responsive hydrogels | Convenient (liquid at room temp, gel at body temp), versatile (LCST/UCST systems), widely explored in tissue engineering and drug delivery. | Cytotoxicity from crosslinkers, complex tuning of LCST, and risk of burst drug release. |
[30] [32] [13] [21] [33] |
|
| Magnetic-responsive hydrogels | Enable non-invasive, localized therapy with external magnetic control. |
Dependence on magnetic nanoparticles’ safety and limited field penetration depth. |
[26] [13] |
|
| Chemical Stimuli | pH-responsive hydrogels | Swell, shrink, or degrade with pH changes, allowing targeted drug delivery in inflamed or acidic tissues. | Small pH differences in vivo reduce targeting specificity; buffering weakens response. | [13] [34] |
| Redox-responsive hydrogels | React to oxidative stress (ROS), protecting cells and modulating drug release profiles. | Variable ROS levels across patients and slow reaction kinetics can limit efficacy. | [13] [34] |
|
| Biochemical Stimuli | Enzyme-responsive hydrogels | Use enzyme-cleavable motifs for personalized, biologically triggered responses; enable in-situ degradation and dynamic scaffold remodeling. | Enzyme variability across patients/disease states may cause unpredictable outcomes. | [34] [13] |
| Glucose-responsive hydrogels | Widely studied for diabetes; release therapeutic agents (e.g., insulin) in response to high glucose levels. | Require direct contact with body fluids and often have lag times in drug release. | [34] [51] |
|
| Study | Outcome |
|---|---|
| [145] | Overall success rate was 76.5%. Sensitivity recovery varied (29.4% A-PRF, 41.2% S-PRF, 17.6% BC). |
| [146] | Favorable clinical outcomes with reduced symptoms and restored vitality. Radiographs and CBCT showed periapical healing, root lengthening, canal wall thickening, and dentin formation. |
| [147] | Most teeth survived up to 3 years post-REP. Flare-ups occurred in some cases. Periapical healing was high on PR evaluation (~90%) but lower on CBCT (~50%). Root development was limited. |
| [148] | Pulp sensibility responses were inconsistent; PRF showed best response at 12 months (66.6%). All groups showed good periapical healing, but radiographic differences in root development were not evident. |
| [149] | Significant improvement in sensibility and periradicular healing at 6 and 12 months, with no difference between groups at 12 months. |
|
[150] |
High overall success (91.7%) in children. Success was greater in developmental anomalies (98.4%) than trauma (84.3%). Radiographs showed improved root characteristics, with no significant difference between CGF and BC scaffolds. |
|
[151] |
No groups regained vitality. PRP showed increased root–root area (RRA), though not statistically significant. |
| Study (Ref) | Title | Year | Applications |
|---|---|---|---|
| [152] | Present status and future directions: Imaging techniques for the detection of periapical lesions | 2022 | Detection of periapical lesions throughout the jaws with minimal risk of false positives |
| [167] | The importance of cone-beam computed tomography in endodontic therapy | 2023 | Evaluation of root canal anomalies, complex morphologies, and sex differences for accurate diagnosis and treatment planning |
| [159,164] | “Combined endo-perio lesions” – what is the best treatment? Surgical endodontics | 2021, 2022 | Quantitative evaluation of combined endo-perio lesions and periodontal healing |
| [165] | Surgical endodontics | 2022 | Precise healing assessment through identification of missed canals and root resorption |
| [159,161] | Diagnostic accuracy of CBCT in identifying periapical lesions; Assessment of endodontic treatment and apical periodontitis prevalence using CBCT | 2025, 2024 | Accurate diagnosis of periapical pathology underestimated by conventional radiographs |
| [162] | Evaluation of obturation techniques in primary molars using CBCT | 2025 | Demonstrated CBCT’s utility in 3D assessment of obturation in primary teeth |
| [163] | Evaluation of canal configuration in maxillary first molars with CBCT | 2024 | Accurate follow-up of retreatment and residual filling material quantification |
| Study (Ref) | Title | Year | Significance |
|---|---|---|---|
| [177] | Brushing motion caused no microcracks: a micro-computed tomography study. Clin Oral Investig | 2025 | Demonstrated that brushing motion did not induce dentinal microcracks, using high-resolution micro-CT to visualize crack details, location, and extension. |
| [178] | Marginal adaptation and porosity of calcium silicate-based cements in furcation perforations: a micro-CT comparative study | 2025 | Evaluated sealing ability of different cements, quantifying marginal adaptation, porosity, and gap formation in furcation perforation repair. |
| [172] | Evaluation of Root Canal Cleaning and Irrigant Penetration Using Different Irrigation Protocols: A Combined SEM and Single-Tooth Micro-CT Study | 2025 | Assessed irrigant penetration depth and root canal cleanliness, highlighting differences between activation methods; required radiopaque contrast medium. |
| [174] | Mineral trioxide aggregate obturation quality with two obturation techniques in severe curved root canals – a micro-CT study | 2024 | Compared obturation quality of different MTA techniques, assessing porosity distribution in curved canals with implications for leakage risk. |
| [175] | Comparative Evaluation of Three Calcium Silicate-Based Materials for Direct Pulp Capping: An In Vivo Study in Mice | 2025 | Used micro-CT to evaluate dentin bridge formation, total volume, and internal voids to compare sealing ability of pulp capping materials. |
| [176] | Cleaning protocols to enhance bond strength of fiberglass posts on root canals filled with bioceramic sealer: an in vitro comparative study | 2025 | Investigated cleaning efficiency and its impact on bond strength of fiber posts, with micro-CT providing 3D analysis of sealer removal. |
| Study (Ref) | Title | Year | Significance |
|---|---|---|---|
| [179,180] | An update of the possible applications of magnetic resonance imaging (MRI) in dentistry: A literature review; Correlation between pulp sensibility and magnetic resonance signal intensity following regenerative endodontic procedures in mature necrotic teeth | 2021, 2024 | Explored dental MRI applications; demonstrated correlation between MRI signal intensity and pulp sensibility tests in regenerative endodontic procedures. |
| [157] | Endodontic working length measurements of premolars and molars in high-resolution dental MRI: a clinical pilot study for assessment of reliability and accuracy | 2022 | Confirmed MRI’s ability to provide reliable working length measurements comparable to CBCT. |
| [177] | Magnetic resonance imaging in the diagnosis of periodontal and periapical disease | 2023 | Demonstrated MRI’s potential to characterize radicular cysts and granulomas with slight overestimation of lesion dimensions, showing reliability comparable to histopathology. |
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