Читать книгу Endodontic Materials in Clinical Practice - Группа авторов - Страница 42

In order to improve the clinical outcomes of VPT, several experimental therapies that have shown promise in tissue regeneration elsewhere have been explored. Bioactive glasses composed of silica, sodium oxide, calcium oxide, and phosphorus pentoxide are well studied in biomaterials [200]. Originally, such glasses were used to repair bone fractures in order to stimulate the body's own regenerative capacity. Bioactive glass dissolves in the normal physiological environment and activates genes controlling osteogenesis and growth factor production [201], leading to bone growth of equivalent quality to that of natural bone [202]. Attempts have been made to assess bioactive glasses as pulp‐capping materials [203], but they have never been significantly more successful than their controls [204].

Emdogain is an enamel matrix derivative originating from unerupted porcine tooth buds which contain amelogenins of various weights. It has proved successful in regenerating periodontal tissues when treating infrabony defects caused by periodontal disease [205]. However, the evidence is less convincing for pulpal tissues: the limited animal and human research conducted to this point shows that, at best, it is no better than calcium hydroxide or MTA [206].

There are several different growth factors and naturally occurring bioactive signalling molecules that are sequestered in dentine during tooth development [178] which have been considered for use as pulp‐capping agents [207]. Bone morphogenetic protein‐2 (BMP‐2), a member of the TGF‐β super family, has been approved by the US Food and Drug Administration (FDA) for clinical use in bone grafting [208] and is known to induce differentiation of DPSCs to an odontoblast phenotype [209]. However, very few other recombinant cytokines have made it past the animal research stage to become candidates for clinical trials. Fibroblast growth factor‐2 (FGF‐2)‐incorporated gelatin hydrogels with collagen sponge have been used on the amputated pulp surface of a rat upper first molar [210, 211]; controlled release of FGF‐2 from the hydrogel induced regeneration of pulp tissue and osteodentin‐like hard tissue in the defect area. In vitro research shows that there is huge promise in the use of these naturally occurring bioactive signalling molecules [38].

The therapeutic use of pharmacological inhibitors to modulate epigenetic ‘marks’ on cellular chromatin has also been shown to alter mineralization response, with inhibitors targeted at DNA‐methylation [212] and histone acetylation shown to promote odontoblast‐like cell differentiation and mineralized tissue formation [51, 213]. Acetylation of histone tails on chromatin is controlled by histone deacetylase (HDAC) and histone acetyl‐transferase enzymes, which if altered by HDAC‐inhibitors (HDACis) result in the promotion of gene expression and a change in cell phenotype [214]. Application of HDACis to rat and human DPSC cultures enhanced mineralization processes, accompanied by an upregulation of genes associated with odontoblast differentiation and mineralization, such as TGF‐β1, BMPs, and DSPP [213, 215, 216]. In addition to the direct regulation of cellular processes, HDACis also induced bioactive DMC release from dentine [45]. Finally, an in vivo study analysed the development of the dentine–pulp complex after systemic injection of trichostatin A (TSA) into prenatal mice and highlighted an increase in odontoblasts and dentine thickness compared with control samples [217].