Main Article Content

Abstract

3D bioprinting holds significant promise for regenerating complex oral and maxillofacial structures. This review provides an in-depth analysis of current bioprinting strategies, including inkjet, extrusion, and laser-assisted technologies, and their applications in bone, cartilage, and soft tissue reconstruction. Key considerations such as cell viability, scaffold design, and vascularization are examined. The combination of bioinks with stem cells and growth factors has opened new avenues for patient-specific treatments. However, technical challenges such as mechanical strength, integration with native tissues, and regulatory barriers persist. This paper concludes with a vision of clinical translation supported by interdisciplinary collaboration and innovation in biomaterials. 

Keywords

3D bioprinting tissue engineering oral surgery biomaterials regenerative medicine

Article Details

How to Cite
Ameer Hamdi Al-Ameedee (2025) “3D Bioprinting in Oral and Maxillofacial Tissue Engineering: Progress, Challenges, and Future Prospects”, Future Dental Research, 3(2), pp. 57–70. doi:10.57238/fdr.2024.152576.1019.

How to Cite

Ameer Hamdi Al-Ameedee (2025) “3D Bioprinting in Oral and Maxillofacial Tissue Engineering: Progress, Challenges, and Future Prospects”, Future Dental Research, 3(2), pp. 57–70. doi:10.57238/fdr.2024.152576.1019.

References

  1. Bell E. Strategy for the selection of scaffolds for tissue engineering. Tissue Eng. 1995 Jun 1;1(2):163-79. doi: 10.1007/s00586-008-0745-3.
  2. Lee JM, Ng WL, Yeong WY. Resolution and shape in bioprinting: strategizing towards complex tissue and organ printing. Appl Phys Rev. 2019 Mar 1;6(1):1. doi: 10.1063/1.5053909.
  3. Ghantous Y, Nashef A, Mohanna A, Abu-El-Naaj I. Three-dimensional technology applications in maxillofacial reconstructive surgery: current surgical implications. Nanomaterials. 2020 Dec 16;10(12):2523. doi: 10.3390/nano10122523.
  4. Ghantous Y, Nashef A, Mohanna A, Abu-El-Naaj I. Three-dimensional technology applications in maxillofacial reconstructive surgery: current surgical implications. Nanomaterials. 2020 Dec 16;10(12):2523. doi: 10.3390/nano10122523.
  5. Wei Q, An Y, Zhao X, Li M, Zhang J. Three-dimensional bioprinting of tissue-engineered skin: biomaterials, fabrication techniques, challenging difficulties, and future directions: a review. Int J Biol Macromol. 2024 May 1;266:131281. doi: 10.1016/j.ijbiomac.2024.131281.
  6. Rodriguez-Salvador M, Ruiz-Cantu L. Revealing emerging science and technology research for dentistry applications of 3D bioprinting. Int J Bioprint. 2018 Dec 26;5(1):170. doi: 10.18063/ijb.v5i1.E.
  7. Dadhich A, Nilesh K, Shah S, Saluja H. Three-dimensional printing in maxillofacial surgery: a quantum leap in future. Natl J Maxillofac Surg. 2022 Aug 1;13(Suppl 1):S203-11. doi: 10.4103/njms.NJMS_65_20.
  8. Shopova D, Mihaylova A, Yaneva A, Bakova D. Advancing dentistry through bioprinting: personalization of oral tissues. J Funct Biomater. 2023 Oct 20;14(10):530. doi: 10.3390/jfb14100530.
  9. Sztankovics D, Moldvai D, Petővári G, Gelencsér R, Krencz I, Raffay R, Dankó T, Sebestyén A. 3D bioprinting and the revolution in experimental cancer model systems—A review of developing new models and experiences with in vitro 3D bioprinted breast cancer tissue-mimetic structures. Pathol Oncol Res. 2023 Feb 9;29:1610996. doi: 10.3389/pore.2023.1610996.
  10. Roy M, Tran P, Dickens T, Schrand A. Composite reinforcement architectures: A review of field-assisted additive manufacturing for polymers. J Compos Sci. 2019 Dec 18;4(1):1. doi: 10.3390/jcs4010001.
  11. Kantaros A, Ganetsos T, Petrescu FI. Transforming object design and creation: biomaterials and contemporary manufacturing leading the way. Biomimetics. 2024 Jan 12;9(1):48. doi: 10.3390/biomimetics9010048.
  12. Genova T, Roato I, Carossa M, Motta C, Cavagnetto D, Mussano F. Advances on bone substitutes through 3D bioprinting. Int J Mol Sci. 2020 Sep 23;21(19):7012. doi: 10.3390/ijms21197012.
  13. Stanco D, Urbán P, Tirendi S, Ciardelli G, Barrero J. 3D bioprinting for orthopaedic applications: Current advances, challenges and regulatory considerations. Bioprinting. 2020 Dec 1;20:e00103. doi: 10.1016/j.bprint.2020.e00103.
  14. Dizon JR, Gache CC, Cascolan HM, Cancino LT, Advincula RC. Post-processing of 3D-printed polymers. Technol. 2021 Aug 25;9(3):61. doi: 10.3390/technologies9030061.
  15. Wallace ER, Yue Z, Dottori M, Wood FM, Fear M, Wallace GG, Beirne S. Point of care approaches to 3D bioprinting for wound healing applications. Prog Biomed Eng. 2023 May 11;5(2):023002. doi: 10.1088/2516-1091/acceeb.
  16. He J, Zhang C, Ozkan A, Feng T, Duan P, Wang S, Yang X, Xie J, Liu X. Patient-derived tumor models and their distinctive applications in personalized drug therapy. Mech Biol Med. 2023 Dec 1;1(2):100014. doi: 10.1016/j.mbm.2023.100014.
  17. Rajeshirke M, Fidan I, Naikwadi V, Alkunte S, Gupta A, Mohammadizadeh M. Material extrusion–based multi-material 3D printing: a holistic review of recent advances. Int J Adv Manuf Technol. 2025 Jun 19:1-26. doi: 10.1007/s00170-025-15920-1.
  18. Khademhosseini A, Vacanti JP, Langer R. Progress in tissue engineering. Sci Am. 2009 May 1;300(5):64-71. doi: 10.1038/scientificamerican0509-64.
  19. Di Bella C, Fosang A, Donati DM, Wallace GG, Choong PF. 3D bioprinting of cartilage for orthopedic surgeons: reading between the lines. Front Surg. 2015 Aug 13;2:39. doi: 10.3389/fsurg.2015.00039.
  20. Salar Amoli M, EzEldeen M, Jacobs R, Bloemen V. Materials for dentoalveolar bioprinting: Current state of the art. Biomedicines. 2021 Dec 30;10(1):71. doi: 10.3390/biomedicines10010071.
  21. Sheikh Z, Nayak VV, Daood U, Kaur A, Moussa H, Canteenwala A, Michaud PL, de Fátima Balderrama Í, de Oliveira Sousa E, Tovar N, Torroni A. Three-dimensional printing methods for bioceramic-based scaffold fabrication for craniomaxillofacial bone tissue engineering. J Funct Biomater. 2024 Mar 1;15(3):60. doi: 10.20944/preprints202311.1884.v1.
  22. Li N, Guo R, Zhang ZJ. Bioink formulations for bone tissue regeneration. Front Bioeng Biotechnol. 2021 Feb 5;9:630488. doi: 10.3389/fbioe.2021.630488.
  23. Cidonio G, Glinka M, Dawson JI, Oreffo RO. The cell in the ink: Improving biofabrication by printing stem cells for skeletal regenerative medicine. Biomaterials. 2019 Jul 1;209:10-24. doi: 10.1016/j.biomaterials.2019.04.009.
  24. Liang J, Liu P, Yang X, Liu L, Zhang Y, Wang Q, Zhao H. Biomaterial-based scaffolds in promotion of cartilage regeneration: recent advances and emerging applications. J Orthop Transl. 2023 Jul 1;41:54-62. doi: 10.1016/j.jot.2023.08.006.
  25. Yan Z, Liu R, Liu B, Shao Y, Liu M. Molecular dynamics simulation studies of properties, preparation, and performance of silicon carbide materials: a review. Energies. 2023 Jan 20;16(3):1176. doi: 10.3390/en16031176.
  26. Chakraborty J, Majumder N, Sharma A, Prasad S, Ghosh S. 3D bioprinted silk-reinforced Alginate-Gellan Gum constructs for cartilage regeneration. Bioprinting. 2022 Dec 1;28:e00232. doi: 10.1016/j.bprint.2022.e00232.
  27. West NX, Lussi A, Seong J, Hellwig E. Dentin hypersensitivity: pain mechanisms and aetiology of exposed cervical dentin. Clin Oral Investig. 2013 Mar;17(Suppl 1):9-19. doi: 10.29303/jppipa.v11i5.10995.
  28. Sahle M, Wachendörfer M, Palkowitz AL, Nasehi R, Aveic S, Fischer H. A Fibrin-Based Human Multicellular Gingival 3D Model Provides Biomimicry and Enables Long-Term In Vitro Studies. Macromol Biosci. 2024 Feb;24(2):2300162. doi: 10.1002/mabi.202300162.
  29. Carletti E, Motta A, Migliaresi C. Scaffolds for tissue engineering and 3D cell culture. 3D Cell Culture: Methods and Protocols. 2010 Oct 7:17-39. doi: 10.1007/978-1-60761-984-0_2.
  30. Wu Y. Electrohydrodynamic jet 3D printing in biomedical applications. Acta Biomater. 2021 Jul 1;128:21-41. doi: 10.1016/j.actbio.2021.04.036.
  31. Somasekharan LT, Kasoju N, Raju R, Bhatt A. Formulation and characterization of alginate dialdehyde, gelatin, and platelet-rich plasma-based bioink for bioprinting applications. Bioengineering. 2020 Sep 9;7(3):108. doi: 10.3390/bioengineering7030108.
  32. Sundararajan S, Samui AB, Kulkarni PS. Versatility of polyethylene glycol (PEG) in designing solid–solid phase change materials (PCMs) for thermal management and their application to innovative technologies. J Mater Chem A. 2017;5(35):18379-96. doi: 10.1039/C7TA04968D.
  33. Damonte G, Maddalena L, Fina A, Cavallo D, Mueller AJ, Caputo MR, Mariani A, Monticelli O. On novel hydrogels based on poly (2-hydroxyethyl acrylate) and polycaprolactone with improved mechanical properties prepared by frontal polymerization. Eur Polym J. 2022 May 15;171:111226. doi: 10.1016/j.eurpolymj.2022.111226.
  34. Kumar P, Sharma J, Kumar R, Najser J, Frantik J, Manuja A, Sunnam N, Praveenkumar S. Advances in bioink-based 3D printed scaffolds: optimizing biocompatibility and mechanical properties for bone regeneration. Biomater Sci. 2025. doi: 10.3390/jmmp9080285.
  35. Williams DF. There is no such thing as a biocompatible material. Biomaterials. 2014 Dec 1;35(38):10009-14. doi: 10.1016/j.biomaterials.2014.08.035.
  36. Guido S. Shear-induced droplet deformation: Effects of confined geometry and viscoelasticity. Curr Opin Colloid Interface Sci. 2011 Feb 1;16(1):61-70. doi: 10.1016/j.cocis.2010.12.001.
  37. Karvinen J, Kellomäki M. Design aspects and characterization of hydrogel-based bioinks for extrusion-based bioprinting. Bioprinting. 2023 Jul 1;32:e00274. doi: 10.1016/j.bprint.2023.e00274.
  38. Toledano M, Toledano-Osorio M, Carrasco-Carmona Á, Vallecillo C, Toledano R, Medina-Castillo AL, Osorio R. State of the art on biomaterials for soft tissue augmentation in the oral cavity. Part II: Synthetic polymers-based biomaterials. Polymers. 2020 Aug 17;12(8):1845. doi: 10.3390/polym12081845.
  39. Pabst A, Kämmerer PW. Collagen matrices: opportunities and perspectives in oral hard and soft tissue regeneration. Quintessence Int. 2020 Apr 1;51(4). doi: 10.3290/j.qi.a44149.
  40. Reig G, Pulgar E, Concha ML. Cell migration: from tissue culture to embryos. Development. 2014 May 15;141(10):1999-2013. doi: 10.1242/dev.101451.
  41. Wang Z, Zhou X, Sheng L, Zhang D, Zheng X, Pan Y, Yu X, Liang X, Wang Q, Wang B, Li N. Effect of ultrasonic degradation on the structural feature, physicochemical property and bioactivity of plant and microbial polysaccharides: A review. Int J Biol Macromol. 2023 May 1;236:123924. doi: 10.3389/fnut.2022.941524.
  42. Ong CS, Yesantharao P, Huang CY, Mattson G, Boktor J, Fukunishi T, Zhang H, Hibino N. 3D bioprinting using stem cells. Pediatr Res. 2018 Jan;83(1):223-31. doi: 10.1038/pr.2017.252.
  43. Leung BM, Lesher-Perez SC, Matsuoka T, Moraes C, Takayama S. Media additives to promote spheroid circularity and compactness in hanging drop platform. Biomater Sci. 2015;3(2):336-44. doi: 10.1039/C4BM00319E.
  44. Twohig C, Helsinga M, Mansoorifar A, Athirasala A, Tahayeri A, França CM, Pajares SA, Abdelmoniem R, Scherrer S, Durual S, Ferracane J. A dual-ink 3D printing strategy to engineer pre-vascularized bone scaffolds in-vitro. Mater Sci Eng C. 2021 Apr 1;123:111976. doi: 10.1016/j.bmt.2025.100115.
  45. Passier R, Mummery C. Origin and use of embryonic and adult stem cells in differentiation and tissue repair. Cardiovasc Res. 2003 May 1;58(2):324-35. doi: 10.1007/112_0508.
  46. Klangprapan J, Souza GR, Ferreira JN. Bioprinting salivary gland models and their regenerative applications. BDJ Open. 2024 May 30;10(1):39. doi: 10.1038/s41405-024-00219-2.
  47. Mohd N, Razali M, Ghazali MJ, Abu Kasim NH. Current advances of three-dimensional bioprinting application in dentistry: a scoping review. Mater. 2022 Sep 15;15(18):6398. doi: 10.3390/ma15186398.
  48. Li J, Chen M, Fan X, Zhou H. Recent advances in bioprinting techniques: approaches, applications and future prospects. J Transl Med. 2016 Sep 20;14(1):271. doi: 10.1186/s12967-016-1028-0.
  49. Varaprasad K, Karthikeyan C, Yallapu MM, Sadiku R. The significance of biomacromolecule alginate for the 3D printing of hydrogels for biomedical applications. Int J Biol Macromol. 2022 Jul 1;212:561-78. doi: 10.1016/j.ijbiomac.2022.05.157.
  50. Wei Q, An Y, Zhao X, Li M, Zhang J. Three-dimensional bioprinting of tissue-engineered skin: biomaterials, fabrication techniques, challenging difficulties, and future directions: a review. Int J Biol Macromol. 2024 May 1;266:131281. doi: 10.1016/j.ijbiomac.2024.131281.
  51. Terzopoulou Z, Zamboulis A, Koumentakou I, Michailidou G, Noordam MJ, Bikiaris DN. Biocompatible synthetic polymers for tissue engineering purposes. Biomacromolecules. 2022 Apr 19;23(5):1841-63. doi: 10.1021/acs.biomac.2c00047.
  52. Guttridge C, Shannon A, O'Sullivan A, O'Sullivan KJ, O'Sullivan LW. Biocompatible 3D printing resins for medical applications: A review of marketed intended use, biocompatibility certification, and post-processing guidance. Ann 3D Print Med. 2022 Mar 1;5:100044. doi: 10.1016/j.stlm.2021.100044.
  53. Wang X, Mu M, Yan J, Han B, Ye R, Guo G. 3D printing materials and 3D printed surgical devices in oral and maxillofacial surgery: design, workflow and effectiveness. Regen Biomater. 2024;11:rbae066. doi: 10.1093/rb/rbae066.
  54. Zhang HB, Xing TL, Yin RX, Shi Y, Yang SM, Zhang WJ. Three-dimensional bioprinting is not only about cell-laden structures. Chin J Traumatol. 2016 Aug 1;19(04):187-92. doi: 10.1016/j.cjtee.2016.06.007.
  55. Causa F, Netti PA, Ambrosio L. A multi-functional scaffold for tissue regeneration: the need to engineer a tissue analogue. Biomaterials. 2007 Dec 1;28(34):5093-9. doi: 10.1016/j.biomaterials.2007.07.030.
  56. Jovic TH, Combellack EJ, Jessop ZM, Whitaker IS. 3D Bioprinting and the Future of Surgery. Front Surg. 2020 Nov 27;7:609836. doi: 10.3389/fsurg.2020.609836.
  57. Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2011 Jul 15;2(1):403-30. doi: 10.1146/annurev-chembioeng-061010-114257.
  58. Guvendiren M, Molde J, Soares RM, Kohn J. Designing biomaterials for 3D printing. ACS Biomater Sci Eng. 2016 Oct 10;2(10):1679-93. doi: 10.1021/acsbiomaterials.6b00121.
  59. Salar Amoli M, EzEldeen M, Jacobs R, Bloemen V. Materials for dentoalveolar bioprinting: Current state of the art. Biomedicines. 2021 Dec 30;10(1):71. doi: 10.3390/biomedicines10010071.
  60. Placone JK, Mahadik B, Fisher JP. Addressing present pitfalls in 3D printing for tissue engineering to enhance future potential. APL Bioeng. 2020 Mar 1;4(1):023001. doi: 10.1063/1.5127860.
  61. Tümer EH, Erbil HY. Extrusion-based 3D printing applications of PLA composites: a review. Coatings. 2021 Mar 29;11(4):390. doi: 10.3390/jmrt.2025.03.184.
  62. Sekar MP, Budharaju H, Zennifer A, Sethuraman S, Vermeulen N, Sundaramurthi D, Kalaskar DM. Current standards and ethical landscape of engineered tissues—3D bioprinting perspective. J Tissue Eng. 2021 Jul;12:20417314211027677. doi: 10.59298/IAAJB/2025/13118.
  63. Li P, Faulkner A, Medcalf N. 3D bioprinting in a 2D regulatory landscape: gaps, uncertainties, and problems. Law Innov Technol. 2020 Jan 2;12(1):1-29. doi: 10.1080/17579961.2020.1727054.
  64. Zaborovskyy VV, Ustych OV, Popovych TP, Manzyuk VV. Certain ethical issues that arise when using 3D bioprinting technology. W Lek. 2023 Feb 19;76(3):180-5. doi: 10.36740/WLek/203904.
  65. Kantaros A, Ganetsos T, Petrescu FI, Alysandratou E. Bioprinting and intellectual property: Challenges, opportunities, and the road ahead. Bioengineering. 2025 Jan 15;12(1):76. doi: 10.3390/bioengineering12010076.
  66. Bogaards F. Qualitative analysis of Commercial Viability of Bioprinting in the Context of Technical, Economic, and Regulatory Challenges in the Netherlands (Doctoral dissertation). doi: 10.2217/rme-2022-0194.
  67. Pottmann H, Liu Y, Wallner J, Bobenko A, Wang W. Geometry of multi-layer freeform structures for architecture. In: ACM SIGGRAPH 2007 papers. 2007 Jul 29:65-es. doi: 10.1145/1275808.1276458.
  68. Kirillova A, Bushev S, Abubakirov A, Sukikh G. Bioethical and legal issues in 3D bioprinting. Int J Bioprint. 2020 Apr 28;6(3):272. doi: 10.18063/ijb.v6i3.272.
  69. Sekar MP, Budharaju H, Zennifer A, Sethuraman S, Vermeulen N, Sundaramurthi D, Kalaskar DM. Current standards and ethical landscape of engineered tissues—3D bioprinting perspective. J Tissue Eng. 2021 Jul;12:20417314211027677. doi: 10.59298/IAAJB/2025/13118.
  70. Dzobo K, Thomford NE, Senthebane DA, Shipanga H, Rowe A, Dandara C, Pillay M, Motaung KS. Advances in regenerative medicine and tissue engineering: innovation and transformation of medicine. Stem Cells Int. 2018;2018:2495848. doi: 10.1155/2018/2495848.
  71. Tan B, Gan S, Wang X, Liu W, Li X. Applications of 3D bioprinting in tissue engineering: advantages, deficiencies, improvements, and future perspectives. J Mater Chem B. 2021;9(27):5385-413. doi: 10.1039/c9jm10280h.
  72. Zhan H, Ni H, Yu X, Gholipourmalekabadi M, Wang T, Lin K, Pan J, Yuan C. 3D bioprinting in oral and craniomaxillofacial tissue regeneration: progress, challenges, and future directions. Biomed Mater. 2025:e70027. doi: 10.1002/bmm2.70027.
  73. Zhang X, Du S, Han L, Feng X, Yang M. Development and Performance Study of Composite Protein Foaming Agent Based on Human Hair Residue. Sustainability. 2024 Aug 2;16(15):6608. doi: 10.3390/su16156608.
  74. Farah CS, Celentano A, Pantaleo G, Shearston K, Fox S, Seyedasli N, Xaymardan M. Regenerative Approaches in Oral Medicine. In: Regenerative Approaches in Dentistry: An Evidence-Based Perspective. Cham: Springer International Publishing; 2021 Jan 26:197-264. doi: 10.1007/978-3-030-59809-9_10.
  75. Bhat S, Uthappa UT, Altalhi T, Jung HY, Kurkuri MD. Functionalized porous hydroxyapatite scaffolds for tissue engineering applications: a focused review. ACS Biomater Sci Eng. 2021 Sep 9;8(10):4039-76. doi: 10.1021/acsbiomaterials.1c00438.

Similar Articles

You may also start an advanced similarity search for this article.