Tooth loss is a major problem of humanity. It may lead to physical and mental discomfort, compromising the quality of life and social interactions. First attempts of dealing with tooth loss appeared in the 600 AD in Mayan civilization. In 1931 archaeologists found a mandible fragment of a Mayan woman with tooth-shaped pieces of seashell as a substitute for natural lower incisors. Contemporary dental implants are nothing like the Mayan shells. They consist of titanium root with the ability of osseointegration and a prosthetic crown of aesthetic features.
Nonetheless the fairytale of dental implants being the ideal, artificial copy of human teeth has been exposed a long time ago, when the first treatment failures have been reported: osseointegrity failures, periimplantitis, progressive bone loss. There are also several major contradictions for the use of dental implants, so the treatment is not as widely available as it seems. Every researchers’ dream is to design a perfect restoration that would never be rejected by the organism and could efficiently replace the missing hard tissues.
The first attempts of tooth regeneration took place in early 2000′s. Cell delivery was then the main stream of dental tissue regeneration, but the method faced many serious obstacles. First of all autologous embryonic tooth germ are not available for human applications, whereas xenogenic embryonic tooth germ cells are being rejected most of the times by the host organism. As for autologous post natal tooth germ cells, or dental pulp stem cells – they are both of limited accessibility. That is why scientists around the world struggle to find another solution. It looks like they have found at last one of great expectations.
Cell homing is a new method which allows to regenerate anatomically correct teeth in special 3D bioprinted scaffolds. The scaffold is made of poly-ε-caprolactone (80%) and hydroxyapatite (20%) and is infused with growth factors and then inserted into a live organism. It contains many special microchannels to enable the endogenous cell migration.
Scientists from Columbia University College of Dental Medicine in New York have succeeded in growing an anatomically shaped human tooth in just 9 weeks. A permanent mandibular first molar scaffold has been infused with SDF1 and BMP7. SDF1 was selected because of its ability to bind to CXCR4 receptors of multiple cell lineages, among others mesenchymal stem/progenitor cells. Meanwhile BMP7 was chosen owing to its effect on dental pulp cells, fibroblasts and osteoblasts in elaborating mineralization. The growth factors have been inserted into the microchannels by the use of micropipettes. Human mandibular molar scaffolds have been implanted into subcutaneous pouches created surgically in rats’ dorsum. Nine weeks after the surgery the scaffolds were removed from rats’ organisms and prepared for the tissue analysis by special staining.
The analysis revealed that angiogenesis took place without any trouble as well as it confirmed an ectopic mineralization. Putative periodontal ligament has been regenerated as well as the newly formed alveolar bone structure. SDF1 has homed mesenchymal and endothelial stem/progenitor cells, whereas BMP7 had a great influence on osteoblast differentiation. Same scientists managed to regenerate rats’ incisor in its original socket- after the regeneration it was not possible to separate the scaffold from the surrounding tissues, which gives a hope for a perfect integration with hosts’ tissues also in the future human studies.
Cell homing offers a different approach to the dental tissue regeneration. It appears that further investigation may be rewarding in the near future. Will 3D scaffolds become an alternative to contemporary implants?
Written by: Maria Bilińska
1. Anatomically Shaped Tooth and Periodontal Regeneration by Cell Homing Rapid Communication, Biomaterials and Bioengineering K. Kim+, C.H. Lee+, B.K. Kim and J.J. Mao, May 6, 2010
2. Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T (2008). Cell Stem Cell 2:566-575