Regenerative Therapies in Dentistry

Rapid scientific advances continue to contribute to novel therapies and technologies, many of which have the potential to transform dentistry. Regenerative Therapies are a multidisciplinary field encompassing molecular biology, genetics, tissue engineering, and nanotechnology. It has been successfully integrated into different clinical disciplines over the last 20 years. Regenerative dentistry focuses on the regeneration of soft and hard tissues by incorporating tissue engineering approaches. It is an interdisciplinary field that applies the principles of both engineering and life sciences toward developing biological substitutes. It restores, maintains, or improves tissue function.

When Will Dentists Be Able to Use Regenerative Dentistry?

In dentistry, regenerative therapies are thought of as a future rather than a current modality. However, dentists have been using regenerative therapies for decades, one example being vital pulp therapy. Vital pulp therapy was first introduced in the 17th century. It relies on the regenerative and reparative capabilities of the tooth. More recently, clinicians have used other regenerative approaches. For instance, oral surgeons, periodontists, and implantologists have used bone grafting and guided tissue regeneration (GTR) therapies. The well-validated techniques that use biocompatible scaffolds to aid tissue regeneration, for many years. Moreover, although less well-evidenced, regenerative endodontic therapies aim to revitalize the damaged dental pulp. They have now to some extent been clinically translated and have been used by many endodontists and pediatric dentists worldwide. The application of regenerative therapies still produces unpredictable outcomes; thus, clinicians and researchers require keeping abreast of advances in evidence-based regenerative materials.

A Glimpse Into “Regenerative Dentistry”

Advances in regenerative dentistry research over recent years have seen whole tooth bioengineering and the use of dental stem cells in a wide array of promising therapies. The discovery of how epithelial and mesenchymal cells interact to initiate a cascade of developmental processes to generate whole organs initiated many efforts to exploit these processes. These pioneering innovations include the first bioengineered tooth via embryonic and adult cell recombination, the characterization of dental pulp stem cells (DPSCs), the first bioengineered tooth grown in a rat jaw, to more recent experiments fabricating bi-layered hydrogel tooth buds. Tooth primordium forms by combining adult and embryonic stem cells from humans and mice. Furthermore, when surgically transplanted in edentulous areas in mice, these constructs develop and erupt into fully functional teeth. Thus, in principle, tooth organ bioengineering is already a reality.

The Ultimate Goal of Regenerative Dentistry

Although the ultimate goal of regenerative dentistry is to regenerate a whole tooth, studies into tooth regeneration also provide other new therapeutic opportunities. Some focus on regenerating specific dental tissues such as dentine, pulp tissues, or enamel using either cell-based approaches, scaffold-based approaches, or both. One recent example is the demonstration that certain compounds developed for Alzheimer’s disease, namely the small molecule GSK-3 inhibitor tideglusib, can activate dentine reparative mechanisms. Low concentrations of these molecules embedded into injectable collagen sponges which, when placed in contact with vital pulp tissues, stimulated intracellular signaling, stem cell differentiation into odontoblasts, and eventually the production of reparative dentine in its former configuration. It is of particular importance since current materials, mainly tricalcium silicate-based cement, replace dentine rather than regenerate it.

As noted above, pulp regeneration is a regenerative endodontic therapy. It has been clinically translated and documented. With respect to enamel, the cell that forms it, ameloblasts, die after producing it, making enamel rather difficult to regenerate. However, considerable efforts are being made to mimic or regenerate enamel hydroxyapatite crystals via biologically-inspired materials or cell-based approaches.

While these are some examples of many aiming to regenerate specific dental tissues, other groups have focused on exploiting the regenerative potential of DPSCs, a highly pluripotent and accessible cell type. These studies have primarily focused on neural repair, smooth muscles regeneration, bladder tissue repair, retinal tissue repair, and bone regeneration, to name a few.

Dentists in 2030—A Call for Change

Many clinical treatments have emerged from an in-depth understanding of the underlying molecular biology and genetics. Exposing young dentists to these principles is of prime importance. Dental undergraduates forced to primarily focus on the clinical aspects of dentistry and skills acquisition. They are very important. However, due to the current rapid pace of innovation and advances in regenerative dentistry, dentists expose to at least its basics at an early stage. Failing to do so will make it harder for future dentists to catch up.

One of the authors’ personal experiences of studying Regenerative Dentistry at King’s College London highlight some of the salient issues. All first and second-year dental undergraduates study basic biology. However, later years at dental school mainly focus on the clinical aspects of dentistry, leaving basic science marginalized. Students applying for the RD Program have a moderate understanding of molecular biology, genetics, and biomaterial sciences. Lack of early exposure to these subjects as undergraduates leads graduate students to enroll in these postgraduate programs. Because they experience difficulties with the course materials. Eventually hinders their progress and diverts time away from applying knowledge to research. If, however, undergraduate students were provided with sufficient knowledge of the underlying principles of regenerative dentistry, they would have time to focus on research and innovation.