Bioprinted enamel–dentin inlays: a future direction in regenerative dentistry

Abstract

The emergence of stem-cell-derived enamel organoids and dentin-producing dental pulp stem cell constructs presents new possibilities for restoring carious lesions using autologous enamel–dentin inlays. This overview outlines the biological and technological advances supporting this approach and proposes a workflow oriented toward clinical application. The benefits of tissue-based inlays, including inherent biomechanical compatibility, aesthetic accuracy, and potential for biological integration, are contrasted with those of purely artificial materials. Significant regenerative developments include the formation of human enamel organoids and odontoblast-lineage cells in vitro, 3D bioprinting of tooth-shaped constructs with demineralised dentin matrix and poly(ε-caprolactone) scaffolds, and fibre-guiding periodontal ligament scaffolds that restore Sharpey’s fibres in vivo. The mechanical performance of adhesive resin cements, with bond strengths of approximately 4–7 MPa to enamel and dentin, and their durability in reattaching natural tooth fragments, supports the feasibility of bonding biological inlays. Practical considerations include controlling the slow degradation and hydrophobicity of poly(ε-caprolactone) through the use of ceramic or natural polymer additives, employing multi-material 3D printing to co-print mineralized enamel and cell-laden dentin layers, and achieving the desired shade, microstructure, and mechanical properties, exemplified by a compressive strength of approximately 677 MPa for 3D-printed zirconia crowns. Despite regulatory and translational challenges, the integration of digital dentistry, bioprinting, and stem cell science points toward future “grow and glue” restorations that may replace traditional drill-and-fill methods.

Keywords

dental tissue engineering / enamel regeneration / dentin regeneration / 3D bioprinting / dental adhesives / regenerative dentistry / biological restorations

References

[1] Zhao F, Zhang Z, Guo W. The 3-dimensional printing for dental tissue regeneration: the state of the art and future challenges. Front Bioeng Biotechnol. 2024; 12: 1356580.

[2] Ravi V, Murashima-Suginami A, Kiso H, Tokita Y, Huang CL, Bessho K, et al. Advances in tooth agenesis and tooth regeneration. Regen Ther. 2023; 22: 160-8.

[3] Zhang X, Negrini NC, Correia R, Sharpe PT, Celiz AD, Volponi AA. Generating Tooth Organoids Using Defined Bioorthogonally Cross-Linked Hydrogels. ACS Macro Lett. 2024; 13: 1620-6.

[4] Pandya M, Diekwisch TGH. Enamel biomimetics-fiction or future of dentistry. Int J Oral Sci. 2019; 11: 8.

[5] Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, et al. The development of a bioengineered organ germ method. Nat Methods. 2007; 4: 227-30.

[6] Oshima M, Mizuno M, Imamura A, Ogawa M, Yasukawa M, Yamazaki H, et al. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One. 2011; 6: e21531.

[7] Alghadeer A, Hanson-Drury S, Patni AP, Ehnes DD, Zhao YT, Li Z, et al. Single-cell census of human tooth development enables generation of human enamel. Dev Cell. 2023; 58: 2163-80.e9.

[8] Sun M, Wu N, Chen H. Laser-assisted Rapid Mineralization of Human Tooth Enamel. Sci Rep. 2017; 7: 9611.

[9] Jablonski-Momeni A, Heinzel-Gutenbrunner M. Efficacy of the self-assembling peptide P11-4 in constructing a remineralization scaffold on artificially-induced enamel lesions on smooth surfaces. J Orofac Orthop. 2014; 75: 175-90.

[10] Han J, Jeong W, Kim M, Nam S, Park E, Kang H. Demineralized Dentin Matrix Particle-Based Bio-Ink for Patient-Specific Shaped 3D Dental Tissue Regeneration. Polymers (Basel). 2021; 13: 1294.

[11] Fiorillo L. Biomaterials in dentistry: the analogue/digital transition. Explor BioMat-X. 2024; 1: 174-7.

[12] Zhang F, Zuo Y, Zhang K, Gao H, Zhang S, Chen H, et al. Fabrication of Zirconia Ceramic Dental Crowns by Digital Light Processing: Effects of the Process on Physical Properties and Microstructure. 3D Print Addit Manuf. 2024; 11: e1257-70.

[13] Hattar S, Hatamleh MM, Sawair F, Al-Rabab’ah M. Bond strength of self-adhesive resin cements to tooth structure. Saudi Dent J. 2015; 27: 70-4.

[14] Sargod SS, Bhat SS. A 9 year follow-up of a fractured tooth fragment reattachment. Contemp Clin Dent. 2010; 1: 243-5.

[15] Beretta M, Manfredini M, Poli PP, Tansella S, Maiorana C. Full Digital Model-Free Maxillary Prosthetic Rehabilitation by Means of One-Piece Implants: A Proof of Concept Clinical Report with Three-Years Follow Up. Prosthesis. 2022; 4: 202-12.

[16] Çin V, İzgi AD, Kale E, Yilmaz B. Marginal and Internal Fit of Monolithic Zirconia Crowns Fabricated by Using Two Different CAD-CAM Workflows: An In Vitro Study. Prosthesis. 2023; 5: 35-47.

[17] Cicciù M, Cervino G, Terranova A, Risitano G, Raffaele M, Cucinotta F, et al. Prosthetic and Mechanical Parameters of the Facial Bone under the Load of Different Dental Implant Shapes: A Parametric Study. Prosthesis. 2019; 1: 41-53.

[18] Schwendicke F, Frencken JE, Bjørndal L, Maltz M, Manton DJ, Ricketts D, et al. Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal. Adv Dent Res. 2016; 28: 58-67.

[19] Chen Q, Zou B, Lai Q, Wang Y, Zhu K, Deng Y, et al. 3D printing and osteogenesis of loofah-like hydroxyapatite bone scaffolds. Ceram Int. 2021; 47: 20352-61.

[20] Athirasala A, Lins F, Tahayeri A, Hinds M, Smith AJ, Sedgley C, et al. A Novel Strategy to Engineer Pre-Vascularized Full-Length Dental Pulp-like Tissue Constructs. Sci Rep. 2017; 7: 3323.

[21] Fiorillo L. Journal of Dentistry and Multidisciplinary Sciences: A new era of integration and integrity in dental and biomedical research . J Dent Multidiscip Sci. 2025; 1: 1-3.

[22] Thalakiriyawa DS, Dissanayaka WL. Advances in Regenerative Dentistry Approaches: An Update. Int Dent J. 2024; 74: 25-34.

[23] Baldión PA, Velandia-Romero ML, Castellanos JE. Odontoblast-Like Cells Differentiated from Dental Pulp Stem Cells Retain Their Phenotype after Subcultivation. Int J Cell Biol. 2018; 2018: 6853189.

[24] Agarwal S, Mistry LN, Kamath S, Thorat R, Gupta B, Kondkari S. Pioneering the Future of Oral Healthcare: Bioprinting and Its Transformative Clinical Potential in Dentistry. Cureus. 2025; 17: e79030.

[25] Park CH, Rios HF, Taut AD, Padial-Molina M, Flanagan CL, Pilipchuk SP, et al. Image-based, fiber guiding scaffolds: a platform for regenerating tissue interfaces. Tissue Eng Part C Methods. 2014; 20: 533-42.

[26] Han P, Bartold PM, Ivanovski S. The emerging role of small extracellular vesicles in saliva and gingival crevicular fluid as diagnostics for periodontitis. J Periodontal Res. 2022; 57: 219-31.

[27] Jeong M, Radomski K, Lopez D, Liu JT, Lee JD, Lee SJ. Materials and Applications of 3D Printing Technology in Dentistry: An Overview. Dent J (Basel). 2023; 12: 1.