journal article·2021-09-13Open access

In Vivo Evaluation of Decellularized Human Tooth Scaffold for Dental Tissue Regeneration

Ik-Hwan Kim, Mijeong Jeon, Kyounga Cheon, Sun Kim, Han-Sung Jung, Yooseok Shin, Chung Kang, Seong-Oh Kim, Hyung-Jun Choi, Hyo-Seol Lee, Ko Lee, Je Song

Applied Sciences· Volume 11· Issue 18

Abstract

Conventional root canal treatment may result in loss of tooth vitality, which can lead to unfavorable treatment outcomes. Notably, a ceased tooth development of immature permanent teeth with open apices, regeneration of periodontal ligaments (PDL), and pulp is highly expected healing process. For regeneration, the scaffold is one of the critical components that carry biological benefits. Therefore, this study evaluated a decellularized human tooth as a scaffold for the PDL and pulp tissue regeneration. A tooth scaffold was fabricated using an effective decellularization method as reported in previous studies. PDL stem cells (PDLSCs) and dental pulp stem cells (DPSCs) obtained from human permanent teeth were inoculated onto decellularized scaffolds, then cultured to transplant into immunosuppressed mouse. After 9 weeks, PDLSCs and DPSCs that were inoculated onto decellularized tooth scaffolds and cultured in an in vivo demonstrated successful differentiation. In PDLSCs, a regeneration of the cementum/PDL complex could be expected. In DPSCs, the expression of genes related to revascularization and the hard tissue regeneration showed the possibility of pulp regeneration. This study suggested that the potential possible application of decellularized human tooth could be a scaffold in regeneration PDL and pulp tissue along with PDLSCs and DPSCs, respectively, as a novel treatment method.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Tissue Engineering and Regenerative Medicine · Electrospun Nanofibers in Biomedical Applications · Dental Trauma and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatric Dentistry, College of Dentistry, Yonsei University, Seoul 03722, Korea

Oral Science Research Center, College of Dentistry, Yonsei University, Seoul 03722, Korea

Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA

Division in Anatomy & Developmental Biology, Department of Oral Biology, College of Dentistry, Yonsei University, Seoul 03722, Korea

Department of Conservative Dentistry, College of Dentistry, Yonsei University, Seoul 03722, Korea

Department of Pediatric Dentistry, Kyung Hee University Dental Hospital, Seoul 02447, Korea

Institute of Craniofacial Deformity, College of Dentistry, Yonsei University, Seoul 03722, Korea

Funding

Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education · National Institutes of Health/National Institute of Dental and Craniofacial Research

References (73)

Show source-provided references
1. Dental pulp stem cells: Their potential in reinnervation and angiogenesis by using scaffolds10.1016/j.joen.2017.06.001 ↗
2. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth10.1016/j.joen.2008.04.009 ↗
3. Magnesium-containing nanostructured hybrid scaffolds for enhanced dentin regeneration10.1089/ten.tea.2013.0741 ↗
4. Participation of periodontal ligament cells with regeneration of alveolar bone10.1902/jop.2001.72.3.314 ↗
5. Regeneration of teeth using stem cell-based tissue engineering10.1517/14712598.6.1.9 ↗
6. Stem cell-based tooth and periodontal regeneration10.1111/odi.12703 ↗
7. Dental pulp regeneration via cell homing10.1111/iej.12868 ↗
8. Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: A pilot clinical study10.1186/s13287-017-0506-5 ↗
9. Biomaterials in tissue engineering
10. Stem cells in tissue engineering10.1038/35102181 ↗
11. Stem and progenitor cells: Origins, phenotypes, lineage commitments, and transdifferentiations10.1146/annurev.cellbio.17.1.387 ↗
12. Therapeutic potential of dental stem cells10.1177/2041731417702531 ↗
13. Stem cells in dentistry–part i: Stem cell sources10.1016/j.jpor.2012.06.001 ↗
14. Dental mesenchymal stem cells10.1242/dev.134189 ↗
15. Nii, T., and Katayama, Y. (2021). Biomaterial-assisted regenerative medicine. Int. J. Mol. Sci., 22.10.3390/ijms22168657 ↗
16. Role of synthetic extracellular matrix in development of engineered dental pulp10.1163/156856298X00127 ↗
17. Scaffold techniques and designs in tissue engineering functions and purposes: A review10.1155/2019/3429527 ↗
18. Naturally derived proteins and glycosaminoglycan scaffolds for tissue engineering applications10.1016/j.msec.2017.04.016 ↗
19. Scaffolds and cells for tissue regeneration: Different scaffold pore sizes—Different cell effects10.1007/s10616-015-9895-4 ↗
20. Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration10.1016/j.carbpol.2011.07.058 ↗
21. A customized self-assembling peptide hydrogel for dental pulp tissue engineering10.1089/ten.tea.2011.0222 ↗
22. Decellularized tooth bud scaffolds for tooth regeneration10.1177/0022034516689082 ↗
23. Son, H., Jeon, M., Choi, H.J., Lee, H.S., Kim, I.H., Kang, C.M., and Song, J.S. (2019). Decellularized human periodontal ligament for periodontium regeneration. PLoS ONE, 14.10.1371/journal.pone.0221236 ↗
24. Decellularized human dental pulp as a scaffold for regenerative endodontics10.1177/0022034517693606 ↗
25. Stem/progenitor cell–mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model10.1089/ten.tea.2009.0518 ↗
26. Regeneration of dental pulp following pulpectomy by fractionated stem/progenitor cells from bone marrow and adipose tissue10.1016/j.biomaterials.2011.11.056 ↗
27. Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro10.1016/0003-9969(92)90009-W ↗
28. The effects of growth factors on DNA synthesis, proteoglycan synthesis and alkaline phosphatase activity in bovine dental pulp cells10.1016/0003-9969(92)90093-N ↗
29. Platelet-derived growth factor exerts disparate effects on odontoblast differentiation depending on the dimers in rat dental pulp cells10.1007/s00441-003-0839-5 ↗
30. Role of exogenous tgf-β in induction of reparative dentinogenesis in vivo10.1111/j.1600-0722.1998.tb02175.x ↗
31. Dental pulp stem cell migration10.1016/j.joen.2010.08.046 ↗
32. Connective tissues of the periodontium: A summary of current work10.1016/S0174-173X(83)80047-8 ↗
33. Periodontal ligament stem cells for periodontal regeneration10.1007/s40496-015-0060-0 ↗
34. Zhu, W., and Liang, M. (2015). Periodontal ligament stem cells: Current status, concerns, and future prospects. Stem Cells Int., 2015.10.1155/2015/972313 ↗
35. Tissue-engineering-based strategies for regenerative endodontics10.1177/0022034514549809 ↗
36. Regenerative endodontics: A way forward10.1016/j.adaj.2016.01.009 ↗
37. Complete pulp regeneration after pulpectomy by transplantation of cd105+ stem cells with stromal cell-derived factor-110.1089/ten.tea.2010.0615 ↗
38. A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for total pulp regeneration10.5966/sctm.2012-0132 ↗
39. Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte-colony stimulating factor10.1111/odi.12227 ↗
40. Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method10.1006/meth.2001.1262 ↗
41. Scaffold design and fabrication technologies for engineering tissues—State of the art and future perspectives10.1163/156856201744489 ↗
42. Scaffold design for tissue engineering10.1002/1616-5195(20020201)2:2<67::AID-MABI67>3.0.CO;2-F ↗
43. Decellularization of tissues and organs
44. Porzionato, A., Stocco, E., Barbon, S., Grandi, F., Macchi, V., and De Caro, R. (2018). Tissue-engineered grafts from human decellularized extracellular matrices: A systematic review and future perspectives. Int. J. Mol. Sci., 19.10.3390/ijms19124117 ↗
45. Badylak, S.F., Weiss, D.J., Caplan, A., and Macchiarini, P. (2012). Retracted: Engineered Whole Organs and Complex Tissues, Elsevier.10.1016/S0140-6736(12)60073-7 ↗
46. Consequences of ineffective decellularization of biologic scaffolds on the host response10.1016/j.biomaterials.2011.10.054 ↗
47. Comparison of decellularization techniques for preparation of extracellular matrix scaffolds derived from three-dimensional cell culture10.1002/jbm.a.34150 ↗
48. Molecular cloning, expression and immunolocalization of a novel human cementum-derived protein (cp-23)10.1016/j.bone.2005.09.009 ↗
49. Characterization of recombinant human cementum protein 1 (hrcemp1): Primary role in biomineralization10.1016/j.bbrc.2009.04.072 ↗
50. Identification of secreted proteins associated with obesity and type 2 diabetes in psammomys obesus10.1038/ijo.2009.148 ↗
51. Romanos, G.E., Asnani, K.P., Hingorani, D., and Deshmukh, V.L. (2014). Periostin: Role in formation and maintenance of dental tissues. J. Cell. Physiol., 229.10.1002/jcp.24407 ↗
52. Temporal and spatial expressions of type xii collagen in the remodeling periodontal ligament during experimental tooth movement10.1177/00220345950740010501 ↗
53. Extracellular matrix in tooth cementum and mantle dentin: Localization of osteopontin and other noncollagenous proteins, plasma proteins, and glycoconjugates by electron microscopy10.1002/(SICI)1097-0185(199606)245:2<293::AID-AR13>3.0.CO;2-K ↗
54. Temporal and local appearance of alkaline phosphatase activity in early stages of guided bone regeneration. A descriptive histochemical study in humans10.1034/j.1600-0501.2001.012002121.x ↗
55. Comparison of stem-cell-mediated osteogenesis and dentinogenesis10.1177/154405910308201208 ↗
56. Influence of poly-l-lactic acid scaffold’s pore size on the proliferation and differentiation of dental pulp stem cells10.1590/0103-6440201300032 ↗
57. Osteogenic differentiation and mineralization of human exfoliated deciduous teeth stem cells on modified chitosan scaffold10.1016/j.msec.2014.04.048 ↗
58. Cementoblasts maintain expression of osteocalcin in the presence of mineral trioxide aggregate10.1097/00004770-200306000-00007 ↗
59. The roles of vascular endothelial growth factor in bone repair and regeneration10.1016/j.bone.2016.06.013 ↗
60. Vascular tissues are a primary source of bmp2 expression during bone formation induced by distraction osteogenesis10.1016/j.bone.2012.02.017 ↗
61. Co-seeding human endothelial cells with human-induced pluripotent stem cell-derived mesenchymal stem cells on calcium phosphate scaffold enhances osteogenesis and vascularization in rats10.1089/ten.tea.2016.0485 ↗
62. The periodontal ligament: A unique, multifunctional connective tissue10.1111/j.1600-0757.1997.tb00094.x ↗
63. Physiology of the human dental pulp10.1016/0030-4220(71)90258-1 ↗
64. Dental tissue regeneration–a mini-review10.1159/000314530 ↗
65. Pulp and periodontal tissue repair-regeneration or tissue metaplasia after dental trauma. A review10.1111/j.1600-9657.2011.01058.x ↗
66. An update on clinical regenerative endodontics10.1111/etp.12040 ↗
67. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing10.1089/ten.tea.2010.0181 ↗
68. A brief historical perspective on dental implants, their surface coatings and treatments10.2174/1874210601408010050 ↗
69. Pulp development, repair, and regeneration: Challenges of the transition from traditional dentistry to biologically based therapies10.1016/j.joen.2014.01.018 ↗
70. Tooth repair and regeneration10.1007/s40496-018-0196-9 ↗
71. Fully functional bioengineered tooth replacement as an organ replacement therapy10.1073/pnas.0902944106 ↗
72. The development of a bioengineered organ germ method10.1038/nmeth1012 ↗
73. Tooth regeneration: Insights from tooth development and spatial-temporal control of bioactive drug release10.1007/s12015-019-09940-0 ↗