The advancement of 3D-printed scaffolds has revolutionized periodontal regeneration by offering patient-specific solutions that enhance bone formation and tissue integration. Various biomaterials, including tricalcium phosphate (TCP), hydroxyapatite (HA), polycaprolactone (PCL), and titanium-based composites, have been explored for their biocompatibility and osteogenic potential. Strategies such as growth factor incorporation, hydrogel-based scaffolds, and guided bone regeneration (GBR) membranes have shown promising results in enhancing cellular response and mechanical stability. Custom-designed scaffolds, fabricated using medical imaging and CAD-based workflows, provide superior structural adaptation to periodontal defects, promoting vascularization and periodontal ligament alignment.
Despite significant progress, challenges remain in optimizing scaffold degradation, enhancing mechanical properties, and ensuring long-term biocompatibility. Emerging bioprinting technologies, incorporating periodontal ligament cells and bioactive hydrogels, are being investigated to further improve tissue regeneration outcomes. Future research will focus on refining biomaterial compositions and scaffold architectures to enhance the efficacy of periodontal regeneration.
Introduction
Overview
Periodontal disease causes progressive destruction of supporting dental tissues. Traditional treatments manage disease but rarely regenerate lost structures. 3D printing and tissue engineering offer promising solutions by creating custom, biologically active scaffolds that can support full regeneration of the periodontium (gingiva, cementum, periodontal ligament, and alveolar bone).
Key Concepts and Advances
1. Role of 3D Printing in Periodontal Repair
Enables patient-specific scaffold fabrication.
Scaffolds mimic the natural extracellular matrix (ECM) and support cell attachment, proliferation, and differentiation.
Advanced designs (e.g., biphasic/triphasic scaffolds) allow sequential release of growth factors for targeted tissue regeneration.
2. Types of 3D Printing Technologies
Inkjet Printing: High precision but limited by material viscosity.
Extrusion & FDM: Common methods for creating strong, biocompatible scaffolds.
Some materials also have antibacterial properties, crucial for infection-prone periodontal sites.
Applications and Research Highlights
Numerous animal and in vitro studies have shown:
Improved bone and ligament regeneration.
Enhanced vascularization and cell differentiation.
Limitations still exist, such as risk of infection, scaffold exposure, and imperfect fiber orientation.
Personalized Regeneration
Custom-designed scaffolds based on CT/CBCT scans align with patient anatomy.
Microchannel architectures help orient PDL fibers and distribute masticatory forces.
Future efforts focus on functional tissue regeneration with biologically integrated scaffolds.
Conclusion
3D printing and tissue scaffolds hold significant promise for advancing periodontal regeneration, offering the potential for precise, patient-specific therapies. However, complete tissue restoration remains a challenge. The selection of suitable biomaterials and the incorporation of bioactive components are crucial for optimizing scaffold functionality and improving tissue regeneration outcomes.
Future studies should focus on refining these technologies to enhance their clinical relevance and therapeutic effectiveness. With the ability to fabricate scaffolds tailored to individual patient needs, 3D printing presents a promising approach to periodontal therapy. Despite current limitations, ongoing advancements in biomaterial development, scaffold engineering, and bioprinting are expected to pave the way for the successful translation of these innovations into clinical practice.
References
[1] Rasperini G, Pilipchuk SP, Flanagan CL, Park CH, Pagni G, Hollister SJ, Giannobile WV. 3D-printed Bioresorbable Scaffold for Periodontal Repair. J Dent Res. 2015 Sep;94(9 Suppl):153S-7S. doi: 10.1177/0022034515588303. Epub 2015 Jun 29. PMID: 26124215.
[2] Dagar M, Chaudry K, Shukla P, Joshi CS, Shiwach R, Narayan RR. Scaffolds in periodontal regeneration- A brief review. J Orofac Health Sci 2024;11(3):93-102.
[3] Hou, Y., Li, Y., Xiao, C., Xu, M., Zhao, G., Shu, Q., Yang, H., & Wang, C. (2024). Research on 3D-Printed FGF2-PLGA/PLGA-nHA-BMP9 Biphasic Scaffolds with Sequential Delivery of FGF2 and BMP9 in Promoting Periodontal Ligament Cells’ Proliferation and Differentiation. https://doi.org/10.21203/rs.3.rs-4132541/v1
[4] Katkar RA, Taft RM, Grant GT. 3D volume rendering and 3D printing (Additive manufacturing) Dent Clin North Am. 2018;62:393–402. doi: 10.1016/j.cden.2018.03.003.
[5] Sufaru I-G, Macovei G, Stoleriu S, Martu M-A, Luchian I, Kappenberg-Nitescu D-C, Solomon SM. 3D Printed and Bioprinted Membranes and Scaffolds for the Periodontal Tissue Regeneration: A Narrative Review. Membranes. 2022; 12(9):902. https://doi.org/10.3390/membranes12090902
[6] Li, C., Xu, X., Gao, J. et al. 3D printed scaffold for repairing bone defects in apical periodontitis. BMC Oral Health 22, 327 (2022). https://doi.org/10.1186/s12903-022-02362-4
[7] Figueiredo, Tarsila De Moura; Do Amaral, Guilherme Castro Lima Silva; Bezerra, Gabriela Neiva; Nakao, Lais Yumi Souza; Villar, Cristina Cunha. Three-dimensional-printed scaffolds for periodontal regeneration: A systematic review. Journal of Indian Society of Periodontology 27(5):p 451-460, Sep–Oct 2023. | DOI: 10.4103/jisp.jisp_350_22
[8] Davidopoulou S, Karakostas P, Batas L, Barmpalexis P, Assimopoulou A, Angelopoulos C, Tsalikis L. Multidimensional 3D-Printed Scaffolds and Regeneration of Intrabony Periodontal Defects: A Systematic Review. Journal of Functional Biomaterials. 2024; 15(2):44. https://doi.org/10.3390/jfb15020044
[9] Sonika S, Esther Nalini H, Renuka Devi R. Quintessential commence of three-dimensional printing in periodontal regeneration-A review. Saudi Dent J. 2023 Nov;35(7):876-882.
[10] Santonocito S, Ferlito S, Polizzi A, Ronsivalle V, Reitano G, Lo Giudice A, et al. Impact exerted by scaffolds and biomaterials in periodontal bone and tissue regeneration engineering: new challenges and perspectives for disease treatment. Explor Med. 2023;4:215–34.
[11] Mangano, C.; Barboni, B.; Valbonetti, L.; Berardinelli, P.; Martelli, A.; Muttini, A.; Bedini, R.; Tetè, S.; Piattelli, A.; Mattioli, M. In Vivo Behavior of a custom-made 3D synthetic bone substitute in sinus augmentation procedures in sheep. J. Oral. Implantol. 2015, 41, 240–250.
[12] Lakkaraju, R.; Guntakandla, V.; Gooty, J.; Palaparthy, R.; Vundela, R.; Bommireddy, V. Three-dimensional printing—A new vista for periodontal regeneration: A review. Int. J. Med. Rev. 2017, 4, 81–85.
[13] Reçica, B.; Popovska, M.; Cana, A.; Bedxeti, L.Z.; Tefiku, U.; Spasovski, S.; Spasovska-Gjorgovska, A.; Kutllovci, T.; Ahmedi, J.F. Use of biomaterials for periodontal regeneration: A review. Open Access Maced J. Med. Sci. 2020, 8, 90–97.
[14] Kim K, Lee CH, Kim BK, Mao JJ. Anatomically shaped tooth and periodontal regeneration by cell homing. J Dent Res. 2010;89:842–7. doi: 10.1177/0022034510370803.
[15] Park CH, Rios HF, Jin Q, Bland ME, Flanagan CL, Hollister SJ, et al. Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces. Biomaterials. 2010;31:5945–52. doi: 10.1016/j.biomaterials.2010.04.027.
[16] Zhao, D.; Dong, H.; Niu, Y.; Fan, W.; Jiang, M.; Li, K.; Wei, Q.; Palin, W.; Zhang, Z. Electrophoretic deposition of novel semi- permeable coatings on 3D-printed Ti-Nb alloy meshes for guided alveolar bone regeneration. Dent. Mat. 2022, 38, 431–443.
[17] Park, C.H.; Rios, H.F.; Jin, Q.; Bland, M.E.; Flanagan, C.L.; Hollister, S.J.; Giannobile, W.V. Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces. Biomaterials 2010, 31, 5945–5952.
[18] Carter, S.S.; Costa, P.F.; Vaquette, C.; Ivanovski, S.; Hutmacher, D.W.; Malda, J. Additive biomanufacturing: An advanced approach for periodontal tissue regeneration. Ann. Biomed. Eng. 2017, 45, 12–22.
[19] Huang, R.Y.; Tai, W.C.; Ho, M.H.; Chang, P.C. Combination of a biomolecule-aided biphasic cryogel scaffold with a barrier membrane adhering PDGF-encapsulated nanofibers to promote periodontal regeneration. J. Periodontal. Re. 2020, 55, 529–538.
[20] Daghrery, A.; de Souza, I.J.; Castilho, M.; Malda, J.; Bottino, M.C. Unveiling the potential of melt electrowritting in regenerative dental medicine. Acta Biomater. 2022, in press.
[21] Carrel, J.P.; Wiskott, A.; Moussa, M.; Rieder, P.; Scherrer, S.; Durual, S. A 3D printed TCP/HA structure as a new osteoconductive scaffold for vertical bone augmentation. Clin. Oral Implant Res. 2016, 27, 55–62
[22] Cho, H.; Tarafder, S.; Fogge, M.; Kao, K.; Lee, C.H. Periodontal ligament stem/progenitor cells with protein-releasing scaffolds for cementum formation and integration on dentin surface. Connect. Tissue Res. 2016, 57, 488–495.
[23] Shim, J.-H.; Won, J.-Y.; Park, J.-H.; Bae, J.-H.; Ahn, G.; Kim, C.-H.; Lim, D.-H.; Cho, D.-W.; Yun, W.-S.; Bae, E.-B.; et al. Effects of 3D-printed polycaprolactone/?-tricalcium phosphate membranes on guided bone regeneration. Int. J. Mol. Sci. 2017, 18, 899.
[24] Dubey, N.; Ferreira, J.A.; Daghrery, A.; Aytac, Z.; Malda, J.; Bhaduri, S.B.; Bottino, M.C. Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration. Acta. Biomater. 2020, 113, 164–176
[25] Hsieh, H.Y.; Yao, C.C.; Hsu, L.F.; Tsai, L.H.; Jeng, J.H.; Young, T.H.; Chen, Y.J. Biological properties of human periodontal ligament cells spheroids cultivated on chitosan and polyvinyl alcohol membranes. J. Formosan. Med. Assoc. 2022.
[26] Bai, L.; Ji, P.; Li, X.; Gao, H.; Li, L.; Wang, C. Mechanical characterization of 3D-printed individualized Ti-Mesh (membrane) for alveolar bone defects. J. Healthc Eng. 2019, 2019, 4231872.
[27] Vaquette, C.; Fan, W.; Xiao, Y.; Hamlet, S.; Hutmacher, D.W.; Ivanovski, S. A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex. Biomaterials 2012, 33, 5560–5573.
[28] Costa, P.F.; Vaquette, C.; Zhang, Q.; Reis, R.L.; Ivanovski, S.; Hutmacher, D.W. Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure. J. Clin. Periodontol. 2014, 41, 283–294.
[29] Wang, C.Y.; Chiu, Y.C.; Lee, A.K.; Lin, Y.A.; Lin, P.Y.; Shie, M.Y. Biofabrication of gingival fibroblast cell-laden collagen/strontium-doped calcium silicate 3D-printed bi-layered scaffold for osteoporotic periodontal regeneration. Biomedicines 2021, 9, 431.
[30] Lee, C.H.; Hajibandeh, J.; Suzuki, T.; Fan, A.; Shang, P.; Mao, J.J. Three-dimensional printed multiphase scaffolds for regeneration of periodontium complex. Tissue Eng. Part A 2014, 20, 1342–1351
[31] CH Park Prototype development for the periodontal model system with the spatial compartmentalization by the additive manufacturingAppl Sci20199214687
[32] S Sprio E Campodoni M Sandri A graded multifunctional hybrid scaffold with superparamagnetic ability for periodontal regenerationInt J Mol Sci201819113604