QuintessencePluridisciplinaire - 2012
Ingénierie tissulaire et sphère oro-faciale
Dr Gottfried Schmalz - Traditional root canal therapy has a success rate of up to 95% under optimal clinical conditions. Nevertheless, the idea of restitutio ad integrum (pulp and dentin regeneration) is tempting for a number of reasons: the wetting of dentin, new dentin formation after caries attack, transmission of pain as an indicator of tissue damage, and active tissue defense mechanisms against invading micro-organisms. Furthermore, in cases of adolescents' teeth with immature roots the risk for root fracture can be reduced if further dentin is produced by a regenerated dental pulp. Already in 1961 Nygaard-Östby showed that connective tissue is able to grow into an empty pulp space. However, new and functional odontoblast-like cells lining the dentin walls had not been shown, which, however, today is considered essential for true pulp regeneration. In the 1990s, the concept of tissue engineering was delineated by Langer and Vacanti involving stem/progenitor cells, scaffolds for cell growth, and signaling molecules. In 2000 and the following years, pulp-derived stem/progenitor cells with the potential to differentiate into odontoblast-like cells, among other cell types, were isolated and characterized. Interestingly, several clinical cases on regeneration of teeth with an immature root and pulp gangrene have been published recently: after antibacterial treatment, provocation of apical bleeding and coverage with MTA cement, continuing root development and dentin apposition were seen on follow-up x-rays. This may be an indication that pulp regeneration is possible.However, dental pulp regeneration still faces a number of challenges; first of all bacteria control. Pulp regeneration will be impaired by bacterial infection. Proof is needed that specific antibiotics or rather non-specific disinfectants have sufficient antimicrobial effects but at the same time do not interfere with the subsequent regenerative events. Mixtures of different antibiotic pastes have been used in this context with promising results.As scaffolds, both natural (e.g. collagen, fibrin) and synthetic materials (e.g. PEG, PLLA) are available. While natural scaffolds are usually biocompatible, the degradation rate is difficult to control. Synthetic materials can be designed with specific material properties, but biocompatibility is often problematic. Furthermore, the scaffold for pulp regeneration should be injectable. Self-assembling peptides have been designed for this purpose with an adequate degradation rate, sufficient mechanical properties and the possibility to couple signaling molecules to the scaffold. Signaling molecules are needed mainly to direct the differentiation of stem cells into odontoblasts (e.g. TGF-?, FGF-2) and to stimulate angiogenesis (e.g. VEGF). Interestingly, a number of growth factors is deposited in dentin and the question is how to utilize them. Finally, stem cells in conjunction with their respective microenvironment (niche) play an important role, and the exploitation of adult stem cell sources is challenging. Although stem/progenitor cells have been isolated from dental pulp, there are many unsolved problems regarding their availability for the specific patient treatment situation, the stability of the genome during extracorporeal handling and quality management. Recent studies, however, have shown that in the periapical area stem cells are present which could be recruited and thus extracorporeal cell handling would become superfluous.After combining these factors, pulp regeneration has been demonstrated in different animal models like mice and dogs. Although a number of pitfalls are still to be expected, it can be envisaged that this technique will be available for patient treatment within the near future.