Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel.
Promoting Induced Pluripotent Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel.
复制标题
DOI：
10.1038/s41598-017-18415-6
复制
发表时间：
2018-01-08
影响因子：
4.6
通讯作者：
Lo WL
中科院分区：
文献类型：
--
作者：
Chien KH;Chang YL;Wang ML;Chuang JH;Yang YC;Tai MC;Wang CY;Liu YY;Li HY;Chen JT;Kao SY;Chen HL;Lo WL
牙周病可引起牙槽骨、牙周韧带和牙骨质的严重破坏，甚至导致进行性口腔功能障碍。牙周组织再生是牙周病治疗的最终目标，以重建牙周组织的结构和功能。然而，再生效率低，可能是由于缺乏适当的牙周微环境。在这项研究中，我们应用了可注射和热敏性壳聚糖/明胶/磷酸甘油水凝胶，为移植的干细胞提供3D环境，并增强干细胞的输送和植入。iPSCs-BMP-6-水凝胶复合物促进骨生成和新结缔组织的分化以及PDL形成。在上颌骨-磨牙缺损的动物模型中，iPSCs-BMP-6-水凝胶处理组显示出显著的矿化，骨体积、骨小梁数量和骨小梁厚度增加。iPSCs和BMP-6的协同作用增加了骨和牙骨质的形成。IPSCs-BMP-6-水凝胶处理的动物显示新的骨合成（增加的ALP和TRAP阳性细胞）、新的PDL再生（通过Masson三色染色和定性测定显示）和降低的炎性细胞因子水平。这些发现表明，水凝胶包封的iPSCs与BMP-6结合提供了一种新的策略，以增强牙周再生。这种组合不仅促进了干细胞衍生的移植物植入，而且最大限度地减少了炎症的进展，这导致了牙周再生的可能性很高。
Periodontal disease may cause considerable destruction of alveolar bone, periodontal ligaments (PDLs) and cementum and even lead to progressive oral dysfunction. Periodontal tissue regeneration is the ultimate goal of periodontal disease treatment to reconstruct both structures and functions. However, the regenerative efficiency is low, possibly due to the lack of a proper periodontal microenvironment. In this study, we applied an injectable and thermosensitive chitosan/gelatin/glycerol phosphate hydrogel to provide a 3D environment for transplanted stem cells and to enhance stem cell delivery and engraftment. The iPSCs-BMP-6-hydrogel complex promoted osteogenesis and the differentiation of new connective tissue and PDL formation. In animal models of maxillary-molar defects, the iPSCs-BMP-6-hydrogel-treated group showed significant mineralization with increased bone volume, trabecular number and trabecular thickness. Synergistic effects of iPSCs and BMP-6 increased both bone and cementum formation. IPSCs-BMP-6-hydrogel-treated animals showed new bone synthesis (increased ALP- and TRAP-positive cells), new PDL regeneration (shown through Masson’s trichrome staining and a qualification assay), and reduced levels of inflammatory cytokines. These findings suggest that hydrogel-encapsulated iPSCs combined with BMP-6 provide a new strategy to enhance periodontal regeneration. This combination not only promoted stem cell-derived graft engraftment but also minimized the progress of inflammation, which resulted in highly possible periodontal regeneration.
登录
查看更多内容
影响因子：
9.7
作者：
Garripelli, Vivek Kumar;Kim, Jin-Ki;Son, Sejin;Kim, Won Jong;Repka, Michael A.;Jo, Seongbong
通讯作者：
Jo, Seongbong
影响因子：
23.9
作者：
Hiler D;Chen X;Hazen J;Kupriyanov S;Carroll PA;Qu C;Xu B;Johnson D;Griffiths L;Frase S;Rodriguez AR;Martin G;Zhang J;Jeon J;Fan Y;Finkelstein D;Eisenman RN;Baldwin K;Dyer MA
通讯作者：
Dyer MA
影响因子：
14
作者：
Cheng, Yung-Hsin;Lin, Feng-Huei;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
4.9
作者：
Hewitt, Kyle J.;Shamis, Yulia;Garlick, Jonathan A.
通讯作者：
Garlick, Jonathan A.
影响因子：
14
作者：
Chien, Yueh;Liao, Yi-Wen;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa