Bioactive and self-healing smart materials in pulp therapy

INTRODUCTION

The art of pulp therapy has seen revolutionary change in recent decades, particularly in simple pulp treatments like pulpotomy, direct and indirect pulp capping, and regenerative endodontic therapy.^1,2 Pulp therapy was limited by the passive nature of the materials used, like zinc oxide, eugenol, and calcium hydroxide glass ionomers that essentially played a role to cover up the pulp and prevent further microbial invasion.^3,4 While the use of such materials gave symptomatic relief as well as trivial protective effects, the pulpal tissue healing and regeneration were not significantly supported by the bio-inert characteristics.^5,6

Based on increased insight into pulp biology and tissue engineering, material formulation is shifting directions towards modalities compatible with the concept of regenerative medicine and to specific ones, which enhance the biological healing with host tissue integration.^7,8 Bioactive or self-repairing smart materials have been a promising advancement for this purpose. Smart materials can sense change, respond dynamically, and respond to the biological environment, something that makes them different from passive inert materials.^9,10 This thus translates to endodontic materials which can repair themselves, inducing pulp-dentin regeneration and releasing bioactive ions which modulate inflammation and respond to mechanical and chemical changes in the oral environment.^11,12 They are also able to seal microleakage by volumetric expansion.¹³

Mineral Trioxide Aggregate (MTA) and bio-dentine’s cell differentiation-inducing ability help in dentin bridge formation and exhibit greater biocompatibility than agents used earlier, such as calcium hydroxide, which have drawn significant attention among bioactive materials.¹⁴ Such chemicals release ions that induce crystallization of hydroxyapatite and create alkaline conditions that are inhibitory to pathogenic bacteria.¹⁵ Their mechanical strength and seal ability also enable them to resist microleakage and structural fracture.^16,17 Meanwhile, a sophistication layer is formed by the technology of self-healing materials, particularly composites and sealers with microcapsules that release healing agents when cracks propagate.¹⁸

These formulations reduce the likelihood of repeated decay, prolong the life of restorations, and reduce the need for retreatment. Stimulus-sensitive materials constitute another innovation of this paradigm.¹⁹ These materials are designed to modify their behavior when they come into contact with environmental stimuli such as temperature changes, pH drops, or bacterial metabolites to a better fit within cavity walls or pulp exposure sites.²⁰ They can alter rheological properties or release antibacterial compounds, for example. With advancing technology, there is more potential to reduce invasiveness while tailoring treatments to the individual needs of clinical conditions. Herein, the mechanisms, composition, clinical performance, and future outlook of bioactive and self-healing smart materials used in pulp therapy are outlined. Through enhanced long-term pulp preservation and biologically driven dentistry, this establishes the platform for material innovation towards future clinical integration.

METHODS

A narrative synthesis approach was used for this review, which was based on pertinent peer-reviewed literature published in English between 2012 and 2025. It was a non-systematic approach. ScienceDirect, PubMed, Scopus, ProQuest, and Google Scholar were among the data sources. “Smart dental materials”, “pulp therapy”, “bioactive materials”, “self-healing composites”, “bio ceramics in endodontics,” and “stimuli-responsive dental materials” were among the keywords. Articles were chosen for inclusion based on their clinical applicability, scientific novelty, or fundamental theory about smart materials in regenerative endodontics or vital pulp therapy. Review papers, case series, in vitro and in vivo investigations, and randomized clinical trials were taken into consideration. Papers that were solely concerned with the orthodontic or restorative uses of smart materials and had no direct connection to pulp therapy were not included. Data regarding composition, material properties, biological responses, and laboratory or clinical results were examined in a few chosen articles. In keeping with a narrative review framework, no formal meta-analysis or evidence grading was done.

DISCUSSION

Contemporary pulp capping agents have tissue modulation and bioactive properties

Nowadays, the use of bioactive materials in pulp therapy has greatly progressed beyond conventional limitations to actively contribute to biological healing.² Mineral Trioxide Aggregate (MTA) is still the gold standard in vital pulp therapy due to its high biocompatibility, consistent dentinal bridge formation, and superior sealing ability.²¹ Its constituents include Portland cement, tricalcium silicate, dicalcium silicate, and bismuth oxide.²² When hydrated, a colloidal gel is formed, progressively solidifying and releasing calcium hydroxide as a byproduct.²³ Given that calcium ions are necessary for mineralization and hydroxyapatite formation, this release adds to its bioactivity.²⁴ Although biodentine and MTA have a similar calcium silicate chemistry, biodentine is frequently regarded as a next-generation substitute because it is easier to handle and sets faster.^25,26 In clinical settings, Biodentine has been demonstrated to produce dentin bridge formation and odontoblastic differentiation that are comparable, while posing fewer discoloration problems.²⁷ The formulation of Biodentine produces a denser microstructure than MTA, which could enhance its long-term mechanical behavior.^28,29 Additionally, it has been demonstrated that both materials increase growth factors that are essential for angiogenesis and pulp healing, such as vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2).³⁰ The regenerative advantages of calcium silicates are being combined with enhanced aesthetics and usability in the development of novel bioactive materials such as calcium phosphate cements and resin-modified bioactive materials.³¹ To preserve the tooth's long-term durability under functional stress, these materials are increasingly being developed to resemble the inorganic phase of dentin and display mechanical characteristics that are similar to those of natural tooth structures.³² Clinical research has demonstrated that the use of bioactive materials in direct pulp capping leads to improved patient outcomes, reduced rates of post-operative sensitivity, and higher success rates.^33,34 Their ongoing advancement is changing the paradigm from merely shielding exposed pulp tissue to actively encouraging dentin-pulp complex regeneration.³⁵

Self-healing dental materials provide both structural repair and functional longevity

Even though bioactive materials enhance the biological response, they eventually have the potential to mechanically fail.³⁶ As a result, self-healing materials are gaining popularity to extend the useful life of interfaces and restorations involving pulp therapy. These materials incorporate autonomous repair concepts, which were initially researched in the domains of civil and aerospace engineering, into dental sealants and resins.³⁷ Microencapsulation is one of the most frequently investigated systems in dentistry.³⁸ Monomeric resins and catalysts are examples of healing agents that are encapsulated in tiny polymeric spheres.³⁹ The capsules burst and release their contents into the microcracks that are created by thermal cycling or masticatory stress.^40,41 Filling the micro gap and restoring structural integrity, the healing agent's polymerization may greatly increase the restoration's lifespan.^18,42 Root canal sealers that contain calcium silicate or hydroxyapatite nanoparticles control ion release and swelling behavior, which can reinforce the seal against bacterial reentry and self-seal voids.^43,44 Developments in polymer chemistry are driving the use of reversible cross-linking or dynamic covalent bonds, which enable the material matrix to change shape in response to stress without exclusively depending on released monomers. These developments are especially helpful in areas of high occlusal load and posterior restorations where marginal degradation is a significant concern.⁴⁵ Although there is a lack of clinical data, laboratory simulations employing thermocycling and load-fatigue tests indicate that self-healing materials can sustain their mechanical performance and sealing capacity for extended periods.⁴⁶ When incorporated into future pulp capping or liner materials, they may provide both mechanical longevity and biological support in a single application.

Smart stimulation for smart, eco-friendly treatments

Construction of stimulus-sensitive systems is one of the latest breakthroughs in intelligent material design. These materials possess great benefit in pulp treatment, where internal feedback mechanisms like bacterial activity, pH changes, and hydration are vital for clinical success.^47,48 They can change their behavior or release certain agents when environmental changes occur. PH-controlled antimicrobial release is one of the best-studied stimulus-sensitive processes in pulp treatment.^49,50 Bacterial metabolism leads to a dramatic reduction in local pH as caries progresses.⁵¹ Materials can be engineered with encapsulated antimicrobial agents like silver nanoparticles, antimicrobial peptides, or chlorhexidine in such a way that these release their content only in this acidic environment.^52,53 This prevents the disruption of the balance of the normal oral microbiota and minimizes the possibility of creating resistant bacterial strains. Another area of research is injectable regenerative endodontic systems and temperature-sensitive hydrogels.^54,55 These types of materials include room temperature liquids that solidify when heated to body temperature and are therefore able to adhere to the intricate pulp chamber structure and eventually form a scaffold that can induce tissue regeneration as well as cell proliferation.^56,57 Some systems also utilize controlled release of growth factors and cell-adhesion peptides to guide stem cell differentiation in place.^58,59 Further still, recent literature has developed photo-sensitive systems in which resin materials incorporate photo-cleavable linkers which, upon actuation at designated wavelengths, liberate drugs or modify material stiffness.⁶⁰ All such developments hint at a day in the not-so-distant future where pulp therapy would become completely tailored as a procedure whereby material changes in a micro-instantaneous basis in conformity to pulp's requirements and microbiological profile, even as this is primarily still in its experimental stage.⁶¹ By synergy, these stimulus-sensitive materials not only augment the outcome of treatment but also provide opportunities for biologically guided and minimally invasive endodontics. With ongoing development and clinical correlation, such materials could be integrated into standard pulp therapy and provide individually adjusted treatments with improved retention of tooth vitality and higher success.

CONCLUSION

Active bio-interactive systems that promote healing and regeneration have actively replaced passive materials as the indicator of pulp therapy's success. Smart materials have made it possible to control pulp exposure and damage in more biologically oriented manners, especially those with bioactive and self-healing characteristics. Bioactive materials that have proved to be effective in controlling inflammation and promoting tissue regeneration include MTA and Bio-dentine. While stimuli-responsive technologies provide pulp treatments with flexibility and accuracy, self-healing materials present a promising pathway toward restoration longevity improvement. For self-healing materials, more research needs to be conducted in evaluating their mechanism of action, in addition to establishing tests that assess their performance.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. Duncan HF. Present status and future directions—Vital pulp treatment and pulp preservation strategies. International Endodontic Journal. 2022;55:497-511.
2. 2. Rajasekar V, Abdalla MM, Huang M, Neelakantan P, Yiu CKY. Next-Generation Biomaterials for Vital Pulp Therapy: Exploring Biological Properties and Dentin Regeneration Mechanisms. Bioengineering. 2025;12(3):248.
3. 3. Abdelaziz AA, Elgohary MS, Atiya MA, Saleh HA, Elgohary Sr MS. A Comparative Study of Different Traditional and Bioactive Indirect Pulp Lining Materials on Post-Operative Dentin Hypersensitivity: An In Vivo Study. Cureus. 2025;17(1).
4. 4. Ali AS, El-Bioumy SY, Mostafa MH. Evaluation of different indirect pulp treatment materials used in deep carious primary molars. Al-Azhar Dental Journal for Girls. 2023;10(2):495-502.
5. 5. Alhusainy A. Long-Term Outcomes of Vital Pulp Therapy in Deep Carious Lesions Using Bioceramic Materials. Journal of pharmacy & bioallied sciences. 2024;16(Suppl 4):S3721-3.
6. 6. El Saied NT, Awad SM, Alhosainy AY. Evaluation of dirEct pulp capping in carious primary molars: a 12-month randomizEd controllEd clinical trial. Journal of Stomatology. 2024;77(4):253-63.
7. 7. Widbiller M, Galler KM. Engineering the Future of Dental Health: Exploring Molecular Advancements in Dental Pulp Regeneration. International Journal of Molecular Sciences. 2023;24(14):11453.
8. 8. Dal-Fabbro R, Swanson WB, Capalbo LC, Sasaki H, Bottino MC. Next-generation biomaterials for dental pulp tissue immunomodulation. Dental materials : official publication of the Academy of Dental Materials. 2023;39(4):333-49.
9. 9. Ballal NV, Duncan HF, Wiedemeier DB, et al. MMP-9 Levels and NaOCl Lavage in Randomized Trial on Direct Pulp Capping. J Dent Res. 2022;101(4):414-9.
10. 10. Chen Y, Zhang F, Fu Q, Liu Y, Wang Z, Qi N. In vitro proliferation and osteogenic differentiation of human dental pulp stem cells in injectable thermosensitive chitosan/β-glycerophosphate/ hydroxyapatite hydrogel. Journal of biomaterials applications. 2016;31(3):317-27.
11. 11. Ducret M, Montembault A, Josse J. Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration. Dental materials : official publication of the Academy of Dental Materials. 2019;35(4):523-33.
12. 12. Atila D, Kumaravel V. Advances in antimicrobial hydrogels for dental tissue engineering: regenerative strategies for endodontics and periodontics. Biomaterials Science. 2023;11(20):6711-47.
13. 13. Wuersching SN, Moser L, Obermeier KT, Kollmuss M. Microleakage of Restorative Materials Used for Temporization of Endodontic Access Cavities. Journal of Clinical Medicine. 2023;12(14):4762.
14. 14. Youssef A-R, Emara R, Taher MM. Effects of mineral trioxide aggregate, calcium hydroxide, biodentine and Emdogain on osteogenesis, Odontogenesis, angiogenesis and cell viability of dental pulp stem cells. BMC oral health. 2019;19:1-9.
15. 15. Lertwisitphon P, Worapasphaiboon Y, Champakanan N. Enhancing elemental release and antibacterial properties of resin-based dental sealants with calcium phosphate, bioactive glass, and polylysine. BMC Oral Health. 2025;25(1):96.
16. 16. Wuersching SN, Moser L, Obermeier KT, Kollmuss M. Microleakage of Restorative Materials Used for Temporization of Endodontic Access Cavities. J Clin Med. 2023;12(14).
17. 17. Dioguardi M, Alovisi M, Sovereto D, et al. Sealing ability and microbial leakage of root-end filling materials: MTA versus epoxy resin: A systematic review and meta-analysis. Heliyon. 2021;7(7).
18. 18. Althaqafi KA, Satterthwaite J, AlShabib A, Silikas N. Synthesis and characterisation of microcapsules for self-healing dental resin composites. BMC Oral Health. 2024;24(1):109.
19. 19. Talaat S, Hashem AA, Abu-Seida A, Abdel Wahed A, Abdel Aziz TM. Regenerative potential of mesoporous silica nanoparticles scaffold on dental pulp and root maturation in immature dog’s teeth: a histologic and radiographic study. BMC Oral Health. 2024;24(1):817.
20. 20. Li H, Huang Y, Zhou X. Intelligent pH-responsive dental sealants to prevent long-term microleakage. Dental materials : official publication of the Academy of Dental Materials. 2021;37(10):1529-41.
21. 21. Nie E, Yu J, Jiang R. Effectiveness of Direct Pulp Capping Bioactive Materials in Dentin Regeneration: A Systematic Review. Materials. 2021;14(22):6811.
22. 22. Kadali N, Alla RK, Guduri V, AV R, MC SS, Raju RV. Mineral Trioxide Aggregate: An overview of composition, properties and clinical applications. Int J Dent Mater. 2020;2(1):11-8.
23. 23. Estrela C, Cintra LTA, Duarte MAH, Rossi-Fedele G, Gavini G, Sousa-Neto MD. Mechanism of action of Bioactive Endodontic Materials. Braz Dent J. 2023;34(1):1-11.
24. 24. Aprillia I, Usman M, Asrianti D. Comparison of calcium ion release from MTA-Angelus® and Biodentine®. Paper presented at: Journal of Physics: Conference Series; 2018.
25. 25. Celiksoz O, Irmak O. Delayed vs. immediate placement of restorative materials over Biodentine and RetroMTA: a micro-shear bond strength study. BMC Oral Health. 2024;24(1):130.
26. 26. Ravindran V, Jeevanandan G, Marimuthu M, et al. Comparison of mineral trioxide aggregate and biodentine for open apex management in children with nonvital immature permanent teeth: a systematic review. European Journal of General Dentistry. 2022;11(02):084-093.
27. 27. Brizuela M, Daley J. Dental Materials: Biodentine, a Calcium Silicate Bioactive. StatPearls; 2024.
28. 28. Butt N, Talwar S, Chaudhry S, Nawal RR, Yadav S, Bali A. Comparison of physical and mechanical properties of mineral trioxide aggregate and Biodentine. Indian Journal of Dental Research. 2014;25(6):692-7.
29. 29. Zain YAM. Fracture Resistance of Immanture Teeth Filled Without Bioaggregate, Mineral Trioxide, Aggregate and Biodentine-A comparative in Vitro Study, Rajiv Gandhi University of Health Sciences (India); 2018.
30. 30. Koutrouli A, Machla F, Arapostathis K, Kokoti M, Bakopoulou A. “Biological responses of two calcium-silicate-based cements on a tissue-engineered 3D organotypic deciduous pulp analogue”. Dental Materials. 2024;40(5):e14-e25.
31. 31. Abou ElReash A, Hamama H, Abdo W, Wu Q, Zaen El-Din A, Xiaoli X. Biocompatibility of new bioactive resin composite versus calcium silicate cements: an animal study. BMC Oral Health. 2019;19(1):194.
32. 32. Fan J, Wang P, Wang S, et al. Advances in macro-bioactive materials enhancing dentin bonding. Discover Nano. 2025;20(1):40.
33. 33. Sabeti M, Huang Y, Chung YJ, Azarpazhooh A. Prognosis of vital pulp therapy on permanent dentition: a systematic review and meta-analysis of randomized controlled trials. Journal of Endodontics. 2021;47(11):1683-95.
34. 34. Kulkarni P, Tiwari S, Agrawal N, Kumar A, Umarekar P, Bhargava S. Clinical Outcome of Direct Pulp Therapy in Primary Teeth: A Systematic Review and Meta-analysis. Journal of Indian Society of Pedodontics and Preventive Dentistry. 2022;40(2):105-11.
35. 35. Nie E, Yu J, Jiang R. Effectiveness of Direct Pulp Capping Bioactive Materials in Dentin Regeneration: A Systematic Review. Materials (Basel, Switzerland). 2021;14(22).
36. 36. Shafaee H, Alirezaie M, Rangrazi A, Bardideh E. Comparison of the success rate of a bioactive dentin substitute with those of other root restoration materials in pulpotomy of primary teeth: Systematic review and meta-analysis. The Journal of the American Dental Association. 2019;150(8):676-88.
37. 37. Fugolin AP, Pfeifer CS. Engineering a new generation of thermoset self-healing polymers based on intrinsic approaches. JADA Foundational Science. 2022;1:100014.
38. 38. Gan S-N, Shahabudin N. Applications of Microcapsules in Self-Healing Polymeric Materials. In: Salaün F, ed. Microencapsulation - Processes, Technologies and Industrial Applications. Rijeka: IntechOpen; 2019.
39. 39. Wu J, Weir MD, Zhang Q, Zhou C, Melo MA, Xu HH. Novel self-healing dental resin with microcapsules of polymerizable triethylene glycol dimethacrylate and N,N-dihydroxyethyl-p-toluidine. Dental materials : official publication of the Academy of Dental Materials. 2016;32(2):294-304.
40. 40. Fugolin APP, Ferracane JL, Pfeifer CS. "Fatigue-Crack Propagation Behavior in Microcapsule-Containing Self-Healing Polymeric Networks". Materials & design. 2022;223.
41. 41. Goertz JP, DeMella KC, Thompson BR, White IM, Raghavan SR. Responsive capsules that enable hermetic encapsulation of contents and their thermally triggered burst-release. Materials Horizons. 2019;6(6):1238-43.
42. 42. Yahyazadehfar M, Huyang G, Wang X, Fan Y, Arola D, Sun J. Durability of self-healing dental composites: A comparison of performance under monotonic and cyclic loading. Materials Science and Engineering: C. 2018;93:1020-6.
43. 43. Bukhary S, Alkahtany S, AlDabeeb D. The Effect of Silver Nanoparticles on Bond Strength of Calcium Silicate-Based Sealer: An In Vitro Study. Applied Sciences. 2024;14(21):9817.
44. 44. Shafie RAE, Mahran AH, Nabeel M. Effect of Calcium Hydroxide Nanoparticles Incorporation on the Physical Properties of Root Canal Sealer.(In Vitro Study). Journal of Fundamental and Clinical Research. 2022;2(2):141-56.
45. 45. Alfaer AS, Hasousah SQ, Alhayani WA, Alhumayed JS, Alazmi AO. Wear Patterns in Modern Dental Materials Used in Extensive Tooth Replacement Treatments; 2025.
46. 46. Mutluay MM, Yahyazadehfar M, Ryou H, Majd H, Do D, Arola D. Fatigue of the resin-dentin interface: a new approach for evaluating the durability of dentin bonds. Dental materials : official publication of the Academy of Dental Materials. 2013;29(4):437-49.
47. 47. Li M, Lv J, Yang Y. Advances of Hydrogel Therapy in Periodontal Regeneration—A Materials Perspective Review. Gels. 2022;8(10):624.
48. 48. Liu H, Shen Y. Environmental stimuli‐responsive hydrogels in endodontics Advances and perspectives. International Endodontic Journal. 2025;58.
49. 49. Fugolin APP, Huynh B, Rajasekaran SP. Innovations in the Design and Application of Stimuli-Responsive Restorative Dental Polymers. Polymers. 2023;15(16):3346.
50. 50. He Y, Vasilev K, Zilm P. pH-Responsive Biomaterials for the Treatment of Dental Caries-A Focussed and Critical Review. Pharmaceutics. 2023;15(7).
51. 51. Takahashi N, Nyvad B. The Role of Bacteria in the Caries Process:Ecological Perspectives. Journal of Dental Research. 2011;90(3):294-303.
52. 52. Akram Z, Aati S, Ngo H, Fawzy A. pH-dependent delivery of chlorhexidine from PGA grafted mesoporous silica nanoparticles at resin-dentin interface. Journal of Nanobiotechnology. 2021;19(1):43.
53. 53. Akram Z, Daood U, Aati S, Ngo H, Fawzy AS. Formulation of pH-sensitive chlorhexidine-loaded/mesoporous silica nanoparticles modified experimental dentin adhesive. Materials Science and Engineering: C. 2021;122:111894.
54. 54. Alkandari M, Barai P, Atia GAN, et al. Bioactive Functionalized Chitosan Thermo‐Responsive Hydrogels as Promising Platforms for Therapeutic, Regenerative Oral, and Maxillofacial Applications. Biotechnology Journal. 2025;20(1):e202400653.
55. 55. Liang Z, Li J, Lin H. Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration. Acta Biomaterialia. 2024;181:202-21.
56. 56. Kocak FZ, Talari AC, Yar M, Rehman IU. In-situ forming pH and thermosensitive injectable hydrogels to stimulate angiogenesis: potential candidates for fast bone regeneration applications. International journal of molecular sciences. 2020;21(5):1633.
57. 57. Abbass MMS, El-Rashidy AA, Sadek KM. Hydrogels and Dentin-Pulp Complex Regeneration: From the Benchtop to Clinical Translation. Polymers (Basel). 2020;12(12).
58. 58. Sadaghiani L, Alshumrani AM, Gleeson HB, Ayre WN, Sloan AJ. Growth factor release and dental pulp stem cell attachment following dentine conditioning: An in vitro study. Int Endod J. 2022;55(8):858-69.
59. 59. Jin R, Song G, Chai J, Gou X, Yuan G, Chen Z. Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro. Journal of Tissue Engineering. 2018;9:2041731418817505.
60. 60. Liu H, Shen Y. Environmental stimuli-responsive hydrogels in endodontics: Advances and perspectives. Int Endod J. 2025;58(5):674-84.
61. 61. Meza G, Urrejola D, Saint Jean N, et al. Personalized Cell Therapy for Pulpitis Using Autologous Dental Pulp Stem Cells and Leukocyte Platelet-rich Fibrin: A Case Report. J Endod. 2019;45(2):144-9