Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release

Abstract

Tooth defect and tooth loss are common clinical diseases in stomatology. Compared with the traditional oral restoration treatment, tooth regeneration has unique advantages and is currently the focus of oral biomedical research. It is known that dozens of cytokines/growth factors and other bioactive factors are expressed in a spatial-temporal pattern during tooth development. On the other hand, the technology for spatial-temporal control of drug release has been intensively studied and well developed recently, making control release of these bioactive factors mimicking spatial-temporal pattern more feasible than ever for the purpose of tooth regeneration. This article reviews the research progress on the tooth development and discusses the future of tooth regeneration in the context of spatial-temporal release of developmental factors.

Keywords: Biodegradable materials; Cytokines; Spatial-temporal control of drug release; Tooth development; Tooth regeneration.

Fig. 1

Spatial-temporal expression of developmental signal molecules during tooth development. Tooth morphogenesis is divided into the initiation, bud, cap and bell stages. Expression of the fundamental signal molecules in the epithelium and mesenchyme are shown and corresponding to each stage

Fig. 2

Schematic representation of the bio-inspired dental regeneration strategy. The gene expression pattern during tooth development is obtained by biology and bioinformatics, and the development associated with spatial-temporal specific expression could be approached by using different control release strategies for regeneration purpose, and making the goal of tooth regeneration expectable

Fig. 3

Strategies for tooth regeneration by reactivating developmental cues. A Different control release strategies of secretory factors based on biological materials. a) Self-degradation; b) pH-responsive release; c) Magnetic release; d) Thermal release; e) 3D printing. B Small RNAs are involved in different parts of the gene expression process. C Different turn-on/off systems for spatial-temporal control of gene expression. D In vivo delivery of gene expression system. E Transplantation of genetically modified cells. FUnder the above strategies, cells from different sources can be directed to differentiate into specific cells and eventually achieve tooth regeneration

Fig. 4

In vivo gene delivery strategies. The gene expression systems could be delivered non-virally and virally, both of which have advantages and disadvantages. LV, lentivirus; AV, adenovirus; AAV, adeno-associated virus; Lipid, liposome; ArgNPs, cationic arginine gold nanoparticles