2022, Vol. 26 ›› Issue (30): 4904-4911

Advances focusing on strategies of promoting vascularization in dental pulp regeneration

Wang Ge1, 2, Xie Li1, 2, Tian Weidong1, 2, 3   

Abstract: BACKGROUND: Revascularization plays an important role in tissue engineering. Dental pulp chamber has its unique anatomy structure, which is surrounded by hard dentin. The blood supply of dental pulp only comes from the narrow apical opening, which makes revascularization more difficult in dental pulp regeneration.  
OBJECTIVE: To conclude the research advances focusing on the designs of signal molecules, scaffolds and cells in promoting vascularization in dental pulp regeneration.
METHODS: We searched the articles on PubMed and CNKI databases with the keywords of “dental pulp regeneration, revascularization, growth factor, material, scaffold, dental pulp stem cell, prevascularization, coculture” in Chinese and English, respectively. Finally, 69 articles met the criteria for review.  
RESULTS AND CONCLUSION: (1) Vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor are the most studied pro-angiogenic factors, which promote angiogenesis by promoting the proliferation and migration of endothelial and perivascular cells, the recruitment of stem cells and their differentiation to endothelial cells. (2) To maintain the appropriate concentration of pro-angiogenic factors in the microenvironment, the addition of heparin, laponite and cellulose nanocrystals to the scaffolds can solubilize, encapsulate, adsorb, and covalently cross-link signal molecules, which mimic in vivo storage and release mechanisms. Natural materials including decellularized dental pulp matrix, platelet-rich plasma, and platelet-rich fibrin are rich in bio-active molecules and their structures can protect and control the release of these signal molecules. (3) Different cell sub-populations of dental pulp stem cells have different angiogenic potentials. Moreover, stem cells can be transfected by biological and chemical vectors to improve the cells’ ability to secrete signal molecules and to promote the transformation of stem cells to endothelial cells. Therefore, the angiogenic capacity of transfected cells is significantly enhanced. Co-implantation of stem cells and endothelial cells can also enhance angiogenic capacity. (4) Prevascularization may be the most powerful means to promote rapid vascularization of dental pulp regeneration. In vitro co-culture of endothelial cells and stem cells with a certain ratio can form microtissues containing vascular structures. Microvascular fragments can be obtained by enzymatic digestion of adipose tissue, in which tubular structures and functional cells can promote the development of new blood vessels and anastomosis with host vessels. (5) Current clinical studies on revascularization of dental pulp are limited to dental pulprevascularization, where signal molecules are added while stimulating the formation of blood clots in the root canal and the effects are observed. While other research directions mainly involve in vivo trials in small and large animals, and further clinical trials are still needed to observe regenerative effects, mitigate side effects, and optimize the preparation process.
Key words: dental pulp regeneration, revascularization, growth factor, material, scaffold, dental pulp stem cell, prevascularization, coculture