Scaffold Materials and Dental Stem Cells in Dental Tissue Regeneration
- 65 Downloads
Purpose of Review
Tissue engineering, as a multidisciplinary approach, is a research topic in medicine, but also in dentistry, to build structures, such as enamel, the dentin-pulp complex, the periodontium, or even whole teeth. The purpose of this review is to describe the latest developments in dental tissue engineering, where some of them will change our treatment concepts in dentistry in the near future, and to discuss hurdles and challenges.
Sophisticated scaffold materials for dental tissue engineering can be fabricated today. No longer only bioinert, but tailor-made for specific applications, biomimetic and bioactive through biochemical and physical cues, growth and differentiation factors, they are able to elicit specific cellular responses, and thus control new tissue formation. Dental stem cells can not only be isolated from various sources but used for their paracrine activity, synergistic effects with epithelial cells exploited, and their behavior modulated by epigenetics. A better understanding of the interplay between cell differentiation and immune and inflammatory stimuli is crucial for the regeneration of tissues, which are constantly confronted with microorganisms. Examples for recent developments include commercially available products for the treatment of initial enamel lesions, a pilot clinical study for dentin-pulp complex regeneration, preclinical trials using cell sheets for periodontal regeneration, and the investigation of various cell sources for whole-tooth engineering.
This review highlights recent advances in dental tissue engineering, discusses some of the shortcomings and describes visions and future challenges.
KeywordsStem cells (MeSH ID: D013234) Tissue engineering (MeSH ID: D023822) Regeneration (MeSH ID: D012038)
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 6.Shekhter AB, Fayzullin AL, Vukolova MN, Rudenko TG, Osipycheva VD, Litvitsky PF. Medical applications of collagen and collagen-based materials. Curr Med Chem. 2017;25. https://doi.org/10.2174/0929867325666171205170339.
- 24.• Lv H, Li L, Zhang Y, Chen Z, Sun M, Xu T, et al. Union is strength: matrix elasticity and microenvironmental factors codetermine stem cell differentiation fate. Cell Tissue Res. 2015;361(3):657–68. https://doi.org/10.1007/s00441-015-2190-z. This review provides an overview about the differentiation along with the specific markers in stem cells that are regulated by matrix elasticity. While it explicitly includes effects observed in dental stem cells, it further sheds light on synergistic effects of matrix elasticity combined with other cues on stem cell differentiation. CrossRefPubMedGoogle Scholar
- 27.Kolind K, Kraft D, Boggild T, Duch M, Lovmand J, Pedersen FS, et al. Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures. Acta Biomater. 2014;10(2):641–50. https://doi.org/10.1016/j.actbio.2013.11.006.CrossRefPubMedGoogle Scholar
- 48.Paino F, la Noce M, Tirino V, Naddeo P, Desiderio V, Pirozzi G, et al. Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2 involvement. Stem Cells (Dayton, Ohio). 2014;32(1):279–89. https://doi.org/10.1002/stem.1544.CrossRefGoogle Scholar
- 51.• Yang R, Yu T, Zhou Y. Interplay between craniofacial stem cells and immune stimulus. Stem Cell Res Ther. 2017;8(1):147. https://doi.org/10.1186/s13287-017-0607-1. This review adds to the existing body of evidence regarding the interplay of stem cells with the immune system by focusing on craniofacial stem cells, i.e. dental stem cells together with mesenchymal stem cells derived from gingiva and from jaw bone marrow. CrossRefPubMedPubMedCentralGoogle Scholar
- 63.Gauthier P, Yu Z, Tran QT, Bhatti FU, Zhu X, Huang GT. Cementogenic genes in human periodontal ligament stem cells are downregulated in response to osteogenic stimulation while upregulated by vitamin C treatment. Cell Tissue Res. 2017;368(1):79–92. https://doi.org/10.1007/s00441-016-2513-8.CrossRefPubMedGoogle Scholar
- 64.• About I. “The stem cell fashion”: do we need only stem cells for tissue regeneration? Clin Oral Investig. 2018;22(2):553–4. https://doi.org/10.1007/s00784-017-2316-7. This short letter to the editor raises awareness of the problem that many papers referring to dental stem cells do in fact rather deal with mixed cell populations, and calls for precision with regard to the terminology. CrossRefPubMedGoogle Scholar
- 66.Pisciolaro RL, Duailibi MT, Novo NF, Juliano Y, Pallos D, Yelick PC, et al. Tooth tissue engineering: the importance of blood products as a supplement in tissue culture medium for human pulp dental stem cells. Tissue Eng A. 2015;21(21–22):2639–48. https://doi.org/10.1089/ten.TEA.2014.0617.CrossRefGoogle Scholar
- 67.• Bakopoulou A, Apatzidou D, Aggelidou E, Gousopoulou E, Leyhausen G, Volk J, et al. Isolation and prolonged expansion of oral mesenchymal stem cells under clinical-grade, GMP-compliant conditions differentially affects “stemness” properties. Stem Cell Res Ther. 2017;8(1):247. https://doi.org/10.1186/s13287-017-0705-0 This original research article contributes to the development of standardized GMP-grade protocols for culturing dental stem cells by comparing serum-free with conventional serum-based expansion media for dental and bone marrow stem cell maintenance. CrossRefPubMedPubMedCentralGoogle Scholar
- 69.• Galvez-Martin P, Sabata R, Verges J, Zugaza JL, Ruiz A, Clares B. Mesenchymal stem cells as therapeutics agents: quality and environmental regulatory aspects. Stem Cells Int. 2016;2016:9783408. https://doi.org/10.1155/2016/9783408. This review summarizes the needs and prerequisites for introducing stem cells as advanced therapy medicinal products in clinical therapies, including diagrams of cleanrooms and the quality tests that the cells have to undergo for being used in clinical applications. CrossRefPubMedPubMedCentralGoogle Scholar
- 72.Nakashima M, Nagasawa H, Yamada Y, Reddi AH. Regulatory role of transforming growth factor-beta, bone morphogenetic protein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells. Dev Biol. 1994;162(1):18–28. https://doi.org/10.1006/dbio.1994.1063.CrossRefPubMedGoogle Scholar
- 85.Fan Y, Sun Z, Moradian-Oldak J. Controlled remineralization of enamel in the presence of amelogenin and fluoride. Biomaterials. 2009;30(4):478–83. https://doi.org/10.1016/j.biomaterials.2008.10.019.CrossRefPubMedGoogle Scholar
- 94.Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R, et al. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration. Stem Cells Transl Med. 2013;2(7):521–33. https://doi.org/10.5966/sctm.2012-0132.CrossRefPubMedPubMedCentralGoogle Scholar
- 95.•• Nakashima M, Iohara K, Murakami M, Nakamura H, Sato Y, Ariji Y, et al. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study. Stem Cell Res Ther. 2017;8:61. https://doi.org/10.1186/s13287-017-0506-5. This pilot clinical study demonstrates that the transplantation for dentin-pulp-complex regeneration is possible. CrossRefPubMedPubMedCentralGoogle Scholar
- 106.•• Carter SD, Costa PF, Vaquette C, Ivanovski S, Hutmacher DW, Malda J. Additive biomanufacturing: an advanced approach for periodontal tissue regeneration. Ann Biomed Eng. 2017;45(1):12–22. https://doi.org/10.1007/s10439-016-1687-2. This recent review summarizes the history of periodontal regeneration with a clear focus on currently emerging technologies. It further explains the principles and the application of the cutting-edge technology of 3D printing for periodontal regeneration. CrossRefPubMedGoogle Scholar
- 107.•• Rasperini G, Pilipchuk SP, Flanagan CL, Park CH, Pagni G, Hollister SJ, et al. 3D-printed bioresorbable scaffold for periodontal repair. J Dent Res. 2015;94(9 Suppl):153s–7s. https://doi.org/10.1177/0022034515588303. This original research paper introduces the ground-breaking novelty of a patient-individual, customized scaffold that was compartmentalized according to the specific needs of the single tissues to be regenerated. The article yet is considered a benchmark paper for additive manufacturing scaffolds to be used for periodontal regeneration purposes. CrossRefPubMedGoogle Scholar
- 109.• Bright R, Hynes K, Gronthos S, Bartold PM. Periodontal ligament-derived cells for periodontal regeneration in animal models: a systematic review. J Periodontal Res. 2015;50(2):160–72. https://doi.org/10.1111/jre.12205. This systematic review provides evidence that the use of periodontal ligament-derived cells results in beneficial outcomes for periodontal regeneration in animal models and recommends to move to human studies on the efficacy, safety and feasibility of stem cell delivery. CrossRefPubMedGoogle Scholar