Pulp Vascularization during Tooth Development, Regeneration, and Therapy.

The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The pulp vascular system is not only responsible for nutrient supply and waste removal but also contributes actively to the pulp inflammatory response and subsequent regeneration. This review discusses the underlying mechanisms of pulp vascularization during tooth development, regeneration, and therapeutic procedures, such as tissue engineering and tooth transplantation. Whereas the pulp vascular system is established by vasculogenesis during embryonic development, sprouting angiogenesis is the predominant process during regeneration and therapeutic processes. Hypoxia can be considered a common driving force. Dental pulp cells under hypoxic stress release proangiogenic factors, with vascular endothelial growth factor being one of the most potent. The benefit of exogenous vascular endothelial growth factor application in tissue engineering has been well demonstrated. Interestingly, dental pulp stem cells have an important role in pulp revascularization. Indeed, recent studies show that dental pulp stem cell secretome possesses angiogenic potential that actively contributes to the angiogenic process by guiding endothelial cells and even by differentiating themselves into the endothelial lineage. Although considerable insight has been obtained in the processes underlying pulp vascularization, many questions remain relating to the signaling pathways, timing, and influence of various stress conditions.