Odontogenesis-related developmental microenvironment facilitates deciduous dental pulp stem cell aggregates to revitalize an avulsed tooth

  • Biomaterials. 2021 Dec:279:121223. doi: 10.1016/j.biomaterials.2021.121223.
Hao Guo  1 ,  Bei Li  2 ,  Meiling Wu  1 ,  Wanmin Zhao  3 ,  Xiaoning He  3 ,  Bingdong Sui  3 ,  Zhiwei Dong  3 ,  Ling Wang  4 ,  Songtao Shi  5 ,  Xiaoyao Huang  1 ,  Xuemei Liu  1 ,  Zihan Li  1 ,  Xiaohe Guo  6 ,  Kun Xuan  7 ,  Yan Jin  8
Affiliations
  • 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 2. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: [email protected].
  • 3. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 4. Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, Xi'an, China.
  • 5. South China Center of Craniofacial Stem Cell Research, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong, China.
  • 6. Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
  • 7. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: [email protected].
  • 8. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: [email protected].
PMID: 34736149 DOI: 10.1016/j.biomaterials.2021.121223
Abstract

Harnessing developmental processes for tissue engineering represents a promising yet challenging approach to regenerative medicine. Tooth avulsion is among the most serious traumatic dental injuries, whereas functional tooth regeneration remains uncertain. Here, we established a strategy using decellularized tooth matrix (DTM) combined with human dental pulp stem cell (hDPSC) aggregates to simulate an odontogenesis-related developmental microenvironment. The bioengineered teeth reconstructed by this strategy regenerated three-dimensional pulp and periodontal tissues equipped with vasculature and innervation in a preclinical pig model after implantation into the alveolar bone. These results prompted us to enroll 15 patients with avulsed teeth after traumatic dental injuries in a pilot clinical trial. At 12 months after implantation, bioengineered teeth led to the regeneration of functional teeth, which supported continued root development, in humans. Mechanistically, exosomes derived from hDPSC aggregates mediated the tooth regeneration process by upregulating the odontogenic and angiogenic ability of hDPSCs. Our findings suggest that odontogenic microenvironment engineering by DTM and stem cell aggregates initiates functional tooth regeneration and serves as an effective treatment for tooth avulsion.

Keywords
DTM; Functional tooth regeneration; Odontogenic microenvironment.
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