Stem Cell and Biomaterials Research in Dental Tissue Engineering and Regeneration

The emergence of tissue engineering and regenerative medicine shed new light on the treatment of patients with degenerative disorders. These approaches combine tools from a variety of fields such as stem-cell biology, biomaterials, and developmental biology. Whereas regenerative medicine places more emphasis on cell-based therapy, particularly stem cells, to repair or replace damaged tissues/organs, tissue engineering focuses on using biomaterials with or without cells to make bioartificial tissues or organs. Various sources of stem cells have been identified and used to generate the desired specialized cell or tissue types. These stem cells are classified into 3 main types: ES cells, somatic/adult stem cells, and induced pluripotent stem cells. In addition, endothelial cells and their paracrine factors such as vascular endothelial growth factor were shown to play important roles in mediating angiogenesis to nurture engineered tissues or organs and facilitate host integration. Other growth factors and bioactive molecules such as those included in the FGF, BMP, Shh, Wnt, and Notch signaling pathways dictate various aspects of tooth morphogenesis and maturation, and thus can be used to guide the formation of engineered tooth tissues/organs in the manner recapitulating development. These key components are summarized in Fig. 3. Fig. 3 Key components of organ/tissue engineering. Key components include (1) stem cells (ie, embryonic stem cells, ES cells; somatic/adult stem cells; induced pluripotent stem cells, iPS cells) or any cells with the capacity to form the desired tissue/organ; ... Finally, in order to apply stem-cell–based therapies to the treatment of diseases, the appropriate microenvironment must be identified to guide the development of stem cells through the following 6 steps: To increase survival of stem cells in the recipient/transplant. To integrate the transplanted cells into the surrounding tissue without harming the recipient; research strategies must be created to avoid the problem of immune rejection without long-term use of immunosuppressive drugs. To increase the proliferation of stem cells to generate sufficient amounts of tissue. To induce the differentiation of stem cells into the desired cell type(s). To maintain the differentiated cells and retain their functions throughout the recipient’s life. To remove unwanted cells. ​ KEY POINTS Dental caries and periodontal disease are the most common diseases resulting in tissue loss. To replace or regenerate new tissues, various types of stem cells have been identified, including embryonic, somatic/adult, and induced pluripotent stem cells. Somatic and induced pluripotent stem cells can be obtained from teeth and periodontium. Endothelial cells and their paracrine factors mediate the formation of vasculature into engineered tissues or organs. Growth factors and bioactive molecules dictate various aspects of tooth morphogenesis and maturation and thus can be used to guide the formation of engineered tooth tissues in the manner recapitulating development. Various biomaterials can be chosen when designing a scaffold, including synthetic, natural, degradable and non-degradable materials. Advances in biomaterial sciences including microfabrication, self-assembled biomimetic peptides, and three-dimensional printing hold great promise for whole organ or partial tissue regeneration to replace teeth and periodontium. Acknowledgments Funding: The authors are supported by the NIH/NIDCR. The authors thank Dr Kerstin Seidel for help with figures, and members of the Klein and Desai laboratories for helpful discussions.