journal article·2026-04-18Open access

3D-Printed and Bioprinted Scaffolds in Regenerative Endodontics: A Systematic Review

Hebertt Gonzaga dos Santos Chaves, Diana B. Sequeira, Vilton Cardozo Moreira Dias, Alberto Cabrera-Fernández, João Peça, Francine Benetti, João Miguel Marques dos Santos

Applied Sciences· Volume 16· Issue 8

Abstract

Introduction: Three-dimensional (3D) bioprinting is a promising approach for endodontic tissue engineering, enabling scaffolds with controlled architecture and bioactivity to support pulp regeneration. Objectives: This systematic review assessed the following: “What 3D bioprinting applications are reported in endodontics-related studies?” Materials and Methods: Following PRISMA 2020 guidelines, PubMed/MEDLINE, Scopus, Embase, Cochrane Library, Web of Science, SciELO, LILACS, and Google Scholar were searched up to January 2026 with no date or language limits. Two reviewers independently screened studies; risk of bias in in vitro studies was assessed with the QUIN tool. As only one study reported complete antimicrobial outcomes, an intra-study quantitative comparison (MD, 95% CI) of inhibition halos was performed (not a meta-analysis). Results: From 518 records, nine studies were included. Outcomes mainly addressed physicochemical properties (n = 9), cell viability (n = 7), biocompatibility (n = 5), and cell differentiation (n = 5); antimicrobial activity was evaluated in two studies. Most used hDPSCs and extrusion-based printing, testing calcium silicate composites, alginate hydrogels, functionalized PCL, and modified PLA. Modified PLA scaffolds showed greater antimicrobial activity, strongest with naringin and nHA formulations. Overall risk of bias was moderate (58.33%), largely due to limited reporting of randomization, blinding, and sampling. Conclusion: 3D-bioprinted scaffolds/bioinks generally improved cellular responses and bioactivity, especially with MTA, Biodentine, nHA, or naringin; antimicrobial effects were most evident in functionalized PLA (PLA/NAR and PLA/nHA/NAR).
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Endodontics and Root Canal Treatments · 3D Printing in Biomedical Research · Bone Tissue Engineering Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Restorative Dentistry, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil

Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal

Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal

Department of Stomatology, Endodontic Section, School of Dentistry, University of Sevilla, 41009 Sevilla, Spain

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior · Conselho Nacional de Desenvolvimento Científico e Tecnológico

References (65)

Show source-provided references
1. The application of tissue engineering to regeneration of pulp and dentin in endodontics10.1097/01.don.0000164138.49923.e5 ↗
2. A leptin-loaded poly-ϵ-caprolactone 3D printing scaffold for odontoblastic differentiation in human dental pulp cells
3. Long-term outcome of nonvital immature permanent teeth treated with apexification and corono-radicular adhesive restoration: A case series10.1016/j.joen.2022.06.007 ↗
4. Effectiveness of endodontic tissue engineering in treatment of apical periodontitis: A systematic review10.1111/iej.13784 ↗
5. Treatment outcomes of regenerative endodontic therapy in immature permanent teeth with pulpal necrosis: A systematic review and network meta-analysis10.1111/iej.13999 ↗
6. Treatment of pulpal and apical disease: The European Society of Endodontology (ESE) S3-level clinical practice guideline10.1111/iej.13974 ↗
7. A review of regenerative endodontics: Current protocols and future directions
8. Infection control in teeth with apical periodontitis using a triple antibiotic solution or calcium hydroxide with chlorhexidine: A randomized clinical trial10.1016/j.joen.2018.07.001 ↗
9. Antimicrobial 3D printed gelatin scaffolds for root canal disinfection in regenerative endodontics procedures10.1039/D5BM00440C ↗
10. Tissue engineering application in regenerative endodontics10.21164/pomjlifesci.718 ↗
11. Alginate-xanthan nanocomposite scaffolds incorporating copper-doped bioactive glass for novel tissue engineering potential in regenerative endodontics10.1007/s10876-025-02895-y ↗
12. Effects of 3-dimensional bioprinting alginate/gelatin hydrogel scaffold extract on proliferation and differentiation of human dental pulp stem cells10.1016/j.joen.2019.03.004 ↗
13. Regeneration of pulp-dentin complex using human stem cells of the apical papilla: In vivo interaction with two bioactive materials10.1007/s00784-021-03840-9 ↗
14. In vivo performance of different scaffolds for dental pulp stem cells induced for odontogenic differentiation10.1590/1807-3107bor-2016.vol30.0120 ↗
15. Scaffolds in regenerative endodontics: A review10.4103/1735-3327.192266 ↗
16. Alginate-gelatin encapsulation of human endothelial cells promoted angiogenesis in in vivo and in vitro milieu10.1002/bit.26395 ↗
17. Sequeira, D.B., Diogo, P., Gomes, B.P.F.A., Peça, J., and Santos, J.M. (2024). Scaffolds for dentin–pulp complex regeneration. Medicina, 60.10.3390/medicina60010007 ↗
18. Gelatin as biomaterial for tissue engineering10.2174/0929867324666170511123101 ↗
19. Alginate- and gelatin-based bioactive photocross-linkable hybrid materials for bone tissue engineering10.1016/j.carbpol.2016.11.051 ↗
20. Dentin matrix components extracted with phosphoric acid enhance cell proliferation and mineralization10.1016/j.dental.2015.11.004 ↗
21. A scoping review of root canal revascularization: Relevant aspects for clinical success and tissue formation10.1111/iej.12711 ↗
22. Enhanced adhesion and differentiation of human mesenchymal stem cell inside apatite-mineralized/poly(dopamine)-coated poly(ε-caprolactone) scaffolds by stereolithography10.1039/C6TB01377E ↗
23. The characteristics of mineral trioxide aggregate/polycaprolactone 3-dimensional scaffold with osteogenesis properties for tissue regeneration10.1016/j.joen.2017.01.009 ↗
24. In vitro evaluation of ProRoot MTA, Biodentine, and MM-MTA on human alveolar bone marrow stem cells in terms of biocompatibility and mineralization10.1016/j.joen.2015.05.012 ↗
25. Bioactivity of MTA Plus, Biodentine and an experimental calcium silicate-based cement on human osteoblast-like cells10.1111/iej.12589 ↗
26. Cytocompatibility of Biodentine using a three-dimensional cell culture model10.1111/iej.12485 ↗
27. Three dimensional printed degradable and conductive polymer scaffolds promote chondrogenic differentiation of chondroprogenitor cells10.1039/D0BM00621A ↗
28. Shie, M.Y., Chang, W.C., Wei, L.J., Huang, Y.H., Chen, C.H., Shih, C.T., Chen, Y.W., and Shen, Y.F. (2017). 3D printing of cytocompatible water-based light-cured polyurethane with hyaluronic acid for cartilage tissue engineering applications. Materials, 10.10.3390/ma10020136 ↗
29. Polylactic acid (PLA) controlled delivery carriers for biomedical applications10.1016/j.addr.2016.06.018 ↗
30. 3D printing of PLA/n-HA composite scaffolds with customized mechanical properties and biological functions for bone tissue engineering10.1016/j.compositesb.2021.109192 ↗
31. Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics10.1016/j.dental.2022.07.002 ↗
32. The inhibitory effect of quaternary ammonium salt on bacteria in root canal10.1038/s41598-019-48666-4 ↗
33. A dentin-derived hydrogel bioink for 3D bioprinting of cell-laden scaffolds for regenerative dentistry10.1088/1758-5090/aa9b4e ↗
34. Regenerative endodontic procedures, disinfectants and outcomes: A systematic review10.1177/2050168420963302 ↗
35. Investigation of the early apical release from endodontic hydrogels: A 3D printed model10.1111/iej.14049 ↗
36. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 6.10.1371/journal.pmed.1000097 ↗
37. Chaves, H.G.D.S., Mendes, A.C.S., Titato, P.C.G., Dias, V.C.M., Figueiredo, B., Duarte, M.A.H., Cintra, L.T.A., André, C.B., Morgan, L.F.S.A., and Santos, J.M.M.d. (2026). A comparison of niobium with other radiopacifying agents in endodontic cements: A systematic review of physicochemical properties. Appl. Sci., 16.10.3390/app16041722 ↗
38. Can different agents reduce the damage caused by bleaching gel to pulp tissue? A systematic review of basic research10.5395/rde.2023.48.e39 ↗
39. Fabrication and characterization of 3D-printed polymeric-based scaffold coated with bioceramic and naringin for a potential use in dental pulp regeneration (in vitro study)10.1111/iej.14194 ↗
40. Development and validation of a risk-of-bias tool for assessing in vitro studies conducted in dentistry: The QUIN10.1016/j.prosdent.2022.05.019 ↗
41. Cabrera-Fernández, A., dos Santos Chaves, H.G., Díaz-Cuenca, A., Segura-Egea, J.J., Martín-González, J., Peça, J., Sequeira, D.B., and dos Santos, J.M.M. (2026). Histological tissue response to calcium silicate-based cements assessed in human tooth culture models: A systematic review. J. Funct. Biomater., 17.10.3390/jfb17020078 ↗
42. Efficacy of 3D-printed scaffolds in guided tissue regeneration for combined endo-perio lesions: A clinical and radiographic study10.4103/jpbs.jpbs_12_25 ↗
43. The effects of Biodentine/polycaprolactone three-dimensional scaffold with odontogenesis properties on human dental pulp cells10.1111/iej.12799 ↗
44. Medium-term function of a 3D printed TCP/HA structure as a new osteoconductive scaffold for vertical bone augmentation: A simulation by BMP-2 activation10.3390/ma8052174 ↗
45. Digital micromirror device (DMD)-based 3D printing of poly(propylene fumarate) scaffolds10.1016/j.msec.2015.11.071 ↗
46. 3D printed silicone-hydrogel scaffold with enhanced physicochemical properties10.1021/acs.biomac.5b01722 ↗
47. Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review10.1016/j.biomaterials.2016.01.012 ↗
48. Biodentine(TM) induces TGF-β1 release from human pulp cells and early dental pulp mineralization10.1111/j.1365-2591.2011.01995.x ↗
49. Biodentine induces immortalized murine pulp cell differentiation into odontoblast-like cells and stimulates biomineralization10.1016/j.joen.2012.04.018 ↗
50. Biodentine induces human dental pulp stem cell differentiation through mitogen-activated protein kinase and calcium-/calmodulin-dependent protein kinase II pathways10.1016/j.joen.2013.11.022 ↗
51. Stimulatory effects of the fast setting and suitable degrading Ca–Si–Mg cement on both cementogenesis and angiogenesis differentiation of human periodontal ligament cells10.1039/C5TB00713E ↗
52. Physical characteristics, antimicrobial and odontogenesis potentials of calcium silicate cement containing hinokitiol10.1016/j.msec.2016.04.016 ↗
53. Preparation of copper-containing bioactive glass/eggshell membrane nanocomposites for improving angiogenesis, antibacterial activity and wound healing10.1016/j.actbio.2016.03.011 ↗
54. Properties of an accelerated mineral trioxide aggregate-like root-end filling material10.1016/j.joen.2008.10.023 ↗
55. In vitro bioactivity and mechanical properties of bioactive glass nanoparticles/polycaprolactone composites10.1016/j.msec.2014.09.041 ↗
56. Injectable radiopaque and bioactive polycaprolactone-ceramic composites for orthopedic augmentation10.1002/jbm.b.33336 ↗
57. Development of an antibacterial nanocomposite hydrogel for human dental pulp engineering10.1039/D0TB00989J ↗
58. Multifunctional and biodegradable methacrylated gelatin/Aloe vera nanofibers for endodontic disinfection and immunomodulation10.1016/j.bioadv.2023.213427 ↗
59. Mustafa, S., Meheissen, M.A., Moussa, S., and ElBackly, R. (2025). Effect of ultrasonically activated irrigation protocols used for regenerative endodontics on removal of dual species biofilm in a three-dimensionally printed tooth model: In vitro study. BMC Oral. Health, 25.10.1186/s12903-024-05415-y ↗
60. Regenerative endodontics: A systematic analysis of the failed cases10.1016/j.joen.2019.02.004 ↗
61. Antimicrobial efficacy of triple antibiotic-eluting polymer nanofibers against multispecies biofilm10.1016/j.joen.2017.06.009 ↗
62. Tănase, M., Veres, C., and Szabo, D.-A. (2025). Artificial intelligence in biomedical 3D printing: Mapping the evidence. J. Manuf. Mater. Process, 9.10.3390/jmmp9120407 ↗
63. Pioneering the future of dentistry: AI-driven 3D bioprinting for next-generation clinical applications
64. Advances in 3D printed scaffolds for periodontal regeneration10.1007/s40496-025-00421-7 ↗
65. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews10.1136/bmj.n71 ↗