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The Use of Bio-Inks and the Era of Bioengineering and Tooth Regeneration

Abstract

Objective:

To review existing literature and provide an update on the current use of Bio-Inks and potential future use.

Material and Methods:

A MeSH keyword search was conducted to find out relevant articles for this short review.

Results:

Bio inks used in 3D printing grafting require various properties essential for the selection. Combining multiple methods and improved properties is essential for developing successful bio-inks for 3D grafting of functional tissues and tooth pulp regeneration from stem cells. To date, researchers have made many efforts to grow teeth based on stem cells and inculcate regeneration of teeth along with surrounding tissues like alveolar bones and periodontal ligaments.

Conclusion:

3D printing with Bio-Inks requires strict adherence to safety protocols for successful outcomes, making it difficult to employ this routinely.

Keywords:
Regeneration; Bioengineering; Tooth; Stem Cells

Introduction

Dental caries is considered to be one of the most common causes of early tooth loss if left untreated [1][1] Hyde S, Dupuis V, Mariri BP, Dartevelle S. Prevention of tooth loss and dental pain for reducing the global burden of oral diseases. Int Dent J 2017; 67(Suppl 2):19-25. https://doi.org/10.1111/idj.12328
https://doi.org/10.1111/idj.12328...
. Therefore, nonbiological (artificial) dental implants are being increasingly used to manage tooth loss [2][2] Greenstein G, Cavallaro J, Romanos G, Tarnow D. Clinical recommendations for avoiding and managing surgical complications associated with implant dentistry: a review. J Periodontol 2008; 79(8):1317-29. https://doi.org/10.1902/jop.2008.070067
https://doi.org/10.1902/jop.2008.070067...
. This treatment modality is standard because the approach focuses on rapid recovery from tooth loss and promises a natural appearance. Nevertheless, differences exist between a natural tooth and an artificial implant, which might frequently cause alveolar tooth loss [2][2] Greenstein G, Cavallaro J, Romanos G, Tarnow D. Clinical recommendations for avoiding and managing surgical complications associated with implant dentistry: a review. J Periodontol 2008; 79(8):1317-29. https://doi.org/10.1902/jop.2008.070067
https://doi.org/10.1902/jop.2008.070067...
.

Around 64% of the patients undergo alveolar bone loss after receiving a dental implant within two months of the treatment [3][3] Cassetta M, Pranno N, Calasso S, Di Mambro A, Giansanti M. Early peri-implant bone loss: a prospective cohort study. Int J Oral Maxillofac Surg 2015; 44(9):1138-45. https://doi.org/10.1016/j.ijom.2015.04.002
https://doi.org/10.1016/j.ijom.2015.04.0...
. To solve the issues, researchers are working on developing cell-based artificial teeth that have the same physiological properties as natural teeth, which can be used as an alternative to dental implants.

Tooth Regeneration

The demand for tissue regeneration and transplantation of tissues and organs is increasing with every passing day. Recent advancements in the field of bioengineering, along with regenerative medicine, have made it possible to regenerate various damaged body parts of functioning organs. 3D bioprinting has made it possible to rehabilitate tissues and organs. It has revolutionized the world of tissue engineering over the past few decades. Since 1990 researchers have been working on skin regeneration, tissue grafting, and bio-fabrication. For decades 3D bioprinting has been used by micro engineers in manufacturing tissue structures from stem cells [4[4] Duarte Campos DF, Zhang S, Kreimendahl F, Köpf M, Fischer H, Vogt M, et al. Hand-held bioprinting for de novo vascular formation applicable to dental pulp regeneration. Connect Tissue Res 2020; 61(2):205-15. https://doi.org/10.1080/03008207.2019.1640217
https://doi.org/10.1080/03008207.2019.16...
,5[5] Han J, Kim DS, Jang H, Kim HR, Kang HW. Bioprinting of three-dimensional dentin-pulp complex with local differentiation of human dental pulp stem cells. J Tissue Eng 2019; 10:2041731419845849. https://doi.org/10.1177/2041731419845849
https://doi.org/10.1177/2041731419845849...
]. In recent decades, 3D printing has been used in the bio-fabrication of functional organs and working tissues advancing the medical field. Bio inks used in 3D printing grafting require various properties essential for the selection. Combining multiple methods and improved properties is necessary for developing successful bio-inks for 3D grafting of functional tissues and tooth pulp regeneration from stem cells [5][5] Han J, Kim DS, Jang H, Kim HR, Kang HW. Bioprinting of three-dimensional dentin-pulp complex with local differentiation of human dental pulp stem cells. J Tissue Eng 2019; 10:2041731419845849. https://doi.org/10.1177/2041731419845849
https://doi.org/10.1177/2041731419845849...
.

To date, researchers have made many efforts to grow teeth based on stem cells and inculcate regeneration of teeth along with surrounding tissues like alveolar bones and periodontal ligaments [6][6] 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(3):227-30. https://doi.org/10.1038/nmeth1012
https://doi.org/10.1038/nmeth1012...
. In addition, bioengineers and oral biologists frequently carry out studies based on tooth germ, aiming to implant stem cells into animals and study successive tooth formation [7][7] Ono M, Oshima M, Ogawa M, Sonoyama W, Hara ES, Oida Y, et al. Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model. Sci Rep 2017; 7:44522. https://doi.org/10.1038/srep44522
https://doi.org/10.1038/srep44522...
. These methods ensure the formation of composite tissue, which is similar to a real-life human tooth (Figure 1).

Figure 1
The Bio-engineering process.

Scaffold-based methods are commonly introduced for artificial tooth regeneration stem cells [8][8] AbdulQader ST, Kannan TP, Rahman IA, Ismail H, Mahmood Z. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells. Mater Sci Eng C Mater Biol Appl 2015; 49:225-33. https://doi.org/10.1016/j.msec.2014.12.070
https://doi.org/10.1016/j.msec.2014.12.0...
. These methods have been reported to be successful in producing somewhat tooth-shaped tissues but failed to produce a patient-specific tooth shape composite tissue composed of pulp, dentin, and enamel [9][9] Chalisserry EP, Nam SY, Park SH, Anil S. Therapeutic potential of dental stem cells. J Tissue Eng 2017; 8:2041731417702531. https://doi.org/10.1177/2041731417702531
https://doi.org/10.1177/2041731417702531...
. Studies focused on achieving structural and compositional similarities between a fabricated tooth and a three-dimensional (3D) patient-specific tooth is pivotal for future clinical applications. Furthermore, there are limitations to tooth germ-based approaches; it is difficult to control the size and shape of the tooth, and it is hard to culture the primary biological sources for the preparation of germ structures. Lastly, scaffold-based methods are not suitable for regenerating tooth alike tissues for the reason that it cannot meticulously replace various cells in a proper pre-defined manner.

In tooth tissue engineering, the shape and design of the tooth must be patient-specific, as it is essential for clinical applications. Different problems can arise during some dental treatments, especially orthodontics. If the size and shape of the tooth are not matched correctly, this can also lead to diverse issues like facial asymmetry, problems in speech pronunciation, and impaired mastication [10[10] Barone S, Neri P, Paoli A, Razionale AV. Design and manufacturing of patient-specific orthodontic appliances by computer-aided engineering techniques. Proc Inst Mech Eng H 2018; 232(1):54-66. https://doi.org/10.1177/0954411917742945
https://doi.org/10.1177/0954411917742945...
,11[11] Marya A. Utilizing aligners to solve the COVID-19-affected orthodontic practice conundrum!. J Adv Oral Res 2020; 11(2):117-9. https://doi.org/10.1177/2320206820942400
https://doi.org/10.1177/2320206820942400...
]. Researchers used Computed tomography CT and applied it to data in 3D bioprinting, which was then converted to a printing code. This successfully illustrated that bio-ink and 3D hybrid bioprinting were used to design 3D patient-specific cellular components of tooth tissue in a pre-defined manner [5][5] Han J, Kim DS, Jang H, Kim HR, Kang HW. Bioprinting of three-dimensional dentin-pulp complex with local differentiation of human dental pulp stem cells. J Tissue Eng 2019; 10:2041731419845849. https://doi.org/10.1177/2041731419845849
https://doi.org/10.1177/2041731419845849...
. Researchers have developed various bio-inks to fabricate different tissues so that their characteristics match those of human body tissues and organs.

Conclusion

Despite 3D printing becoming more affordable in the past few years, there are several costs involved that include materials, equipment maintenance, and the requirement of highly skilled professionals. It also requires strict adherence to safety protocols for successful outcomes, making it difficult to employ this routinely. However, these costs should come down with time, and this technology should have an ever-increasing role in dentistry in the future.

  • Data Availability
    The data used to support the findings of this study can be made available upon request to the corresponding author.

References

  • [1]
    Hyde S, Dupuis V, Mariri BP, Dartevelle S. Prevention of tooth loss and dental pain for reducing the global burden of oral diseases. Int Dent J 2017; 67(Suppl 2):19-25. https://doi.org/10.1111/idj.12328
    » https://doi.org/10.1111/idj.12328
  • [2]
    Greenstein G, Cavallaro J, Romanos G, Tarnow D. Clinical recommendations for avoiding and managing surgical complications associated with implant dentistry: a review. J Periodontol 2008; 79(8):1317-29. https://doi.org/10.1902/jop.2008.070067
    » https://doi.org/10.1902/jop.2008.070067
  • [3]
    Cassetta M, Pranno N, Calasso S, Di Mambro A, Giansanti M. Early peri-implant bone loss: a prospective cohort study. Int J Oral Maxillofac Surg 2015; 44(9):1138-45. https://doi.org/10.1016/j.ijom.2015.04.002
    » https://doi.org/10.1016/j.ijom.2015.04.002
  • [4]
    Duarte Campos DF, Zhang S, Kreimendahl F, Köpf M, Fischer H, Vogt M, et al. Hand-held bioprinting for de novo vascular formation applicable to dental pulp regeneration. Connect Tissue Res 2020; 61(2):205-15. https://doi.org/10.1080/03008207.2019.1640217
    » https://doi.org/10.1080/03008207.2019.1640217
  • [5]
    Han J, Kim DS, Jang H, Kim HR, Kang HW. Bioprinting of three-dimensional dentin-pulp complex with local differentiation of human dental pulp stem cells. J Tissue Eng 2019; 10:2041731419845849. https://doi.org/10.1177/2041731419845849
    » https://doi.org/10.1177/2041731419845849
  • [6]
    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(3):227-30. https://doi.org/10.1038/nmeth1012
    » https://doi.org/10.1038/nmeth1012
  • [7]
    Ono M, Oshima M, Ogawa M, Sonoyama W, Hara ES, Oida Y, et al. Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model. Sci Rep 2017; 7:44522. https://doi.org/10.1038/srep44522
    » https://doi.org/10.1038/srep44522
  • [8]
    AbdulQader ST, Kannan TP, Rahman IA, Ismail H, Mahmood Z. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells. Mater Sci Eng C Mater Biol Appl 2015; 49:225-33. https://doi.org/10.1016/j.msec.2014.12.070
    » https://doi.org/10.1016/j.msec.2014.12.070
  • [9]
    Chalisserry EP, Nam SY, Park SH, Anil S. Therapeutic potential of dental stem cells. J Tissue Eng 2017; 8:2041731417702531. https://doi.org/10.1177/2041731417702531
    » https://doi.org/10.1177/2041731417702531
  • [10]
    Barone S, Neri P, Paoli A, Razionale AV. Design and manufacturing of patient-specific orthodontic appliances by computer-aided engineering techniques. Proc Inst Mech Eng H 2018; 232(1):54-66. https://doi.org/10.1177/0954411917742945
    » https://doi.org/10.1177/0954411917742945
  • [11]
    Marya A. Utilizing aligners to solve the COVID-19-affected orthodontic practice conundrum!. J Adv Oral Res 2020; 11(2):117-9. https://doi.org/10.1177/2320206820942400
    » https://doi.org/10.1177/2320206820942400

Edited by

Academic Editor: Alessandro Leite Cavalcanti

Publication Dates

  • Publication in this collection
    18 July 2022
  • Date of issue
    2022

History

  • Received
    10 Nov 2021
  • Reviewed
    17 Dec 2021
  • Accepted
    19 Dec 2021
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