期刊
CHEMICAL ENGINEERING JOURNAL
卷 431, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.133220
关键词
Periodontal regeneration; Biomineralization; Cell microspheroids; Dental pulp stem cells; TGF-beta 1
资金
- National Natural Science Foundations of China [81871492, 81901053]
- Ten-Thousand Talents Program [QNBJ2019-2]
- Key R&D Plan of Ningxia Hui Autonomous Region [2020BCG01001]
- China Postdoctoral Science Foundation [2020M680263]
- Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences (2020)
- Peking University Medicine Fund of Fostering Young Scholars' Scientific & Technological Innovation
- Fundamental Research Funds for the Central Universities [BMU2018PYB017]
Stem cell therapies using endogenous extracellular matrix show promise in achieving structural and functional periodontal regeneration. MMCMs, developed to mimic native mesenchymal microspheroids, regenerate complete periodontium and promote functional periodontal regeneration through activation of the TGF-beta 1/Smad3 signaling pathway.
Engineering complete periodontal tissue regeneration remains a considerable clinical challenge because the native periodontium is composed of hard mineralized and soft unmineralized tissues. Stem cell therapies that use endogenous extracellular matrix (ECM) have the potential for structural and functional periodontal regeneration. Here, mineralized ECM/dental pulp stem cell microspheroids (MMCMs) mimicking native mesenchymal microspheroid precursors were developed, and showed an enhanced Young's modulus ranging from 0.4 GPa to 1.9 GPa. Furthermore, biomineralization promoted cell viability, inhibited cell apoptosis, and enhanced ECM secretion and osteogenic differentiation potential in dental pulp stem cells. After implantation in the full peri-odontal defect, MMCMs regenerated complete periodontium with native-like hierarchically organized peri-odontal ligament collagen fibers inserted into the newly formed alveolar bone and cementum; they also recruited CD90(+)CD73(+) host mesenchymal stem cells. Mechanistically, MMCMs promoted functional periodontal regen-eration through activation of the transforming growth factor beta 1 (TGF-beta 1)/Smad3 signaling pathway. Inhi-bition of TGF-beta 1 signaling pathway significantly impaired osteogenic potential and matrix secretion of MMCMs, while exogenous TGF-beta 1 treatment enhanced the osteogenesis and periodontal regeneration outcomes of MMCMs. These results indicate the promising application of MMCMs in complex tissue regeneration.
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