Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix
Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix
复制标题
通过调节仿生基质的硬度来完成牙髓牙本质复合物的再生。
DOI：
10.1016/j.actbio.2015.01.029
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发表时间：
2015-04-01
影响因子：
9.7
通讯作者：
Liu, Xiaohua
中科院分区：
文献类型：
--
作者：
Qu, Tiejun;Jing, Junjun;Liu, Xiaohua
龋齿是所有人群中最普遍的慢性疾病之一。利用支架材料进行牙髓组织的再生是一种很有前途的替代受损牙体结构并恢复其生物学功能的方法。然而，目前用于牙髓牙本质再生的支架设计没有考虑到牙髓和牙本质之间的明显差异，因此无法再生完整的牙齿样牙髓牙本质复合体。在这项研究中，我们确定，支架刚度是一个重要的生物物理线索，以调节牙髓干细胞（DPSC）分化。高刚度三维（3D）纳米纤维明胶（NF-明胶）支架上的DPSC具有更有组织的细胞骨架和更大的扩展面积比低刚度NF-明胶支架。在相同的分化培养基中，高刚度的NF-明胶促进DPSC分化形成矿化组织，而低刚度的NF-明胶促进DPSC形成软髓样组织。然后开发了一种简便的方法，将低硬度和高硬度明胶基质整合到单个支架（S支架）中，用于牙髓牙本质复合体再生。4周的体外实验表明，生物矿化只发生在高刚度的周边区域，并形成一个环状结构周围的非矿化的DPSC/S-支架结构的中心区域。将DPSC/S-支架植入裸鼠皮下4周后，成功地再生出类似于天然牙髓的完整牙髓复合物。组织学染色显示，在新形成的牙髓牙本质复合体中形成了大量的细胞外基质（ECM），并且在牙髓组织中观察到了许多血管。总之，这项工作表明，调节NF-明胶支架的刚度是一种成功的方法来再生一个完整的牙齿样牙髓复合物。由Elsevier Ltd.代表Acta Materialia Inc.出版。
Dental caries is one of the most prevalent chronic diseases in all populations. The regeneration of dentin-pulp tissues (pulpodentin) using a scaffold-based tissue engineering strategy is a promising approach to replacing damaged dental structures and restoring their biological functions. However, the current scaffolding design for pulpodentin regeneration does not take into account the distinct difference between pulp and dentin, therefore, is incapable of regenerating a complete tooth-like pulpodentin complex. In this study, we determined that scaffolding stiffness is a crucial biophysical cue to modulate dental pulp stem cell (DPSC) differentiation. The DPSCs on a high-stiffness three-dimensional (3D) nanofibrous gelatin (NF-gelatin) scaffold had more organized cytoskeletons and a larger spreading area than on a low-stiffness NF-gelatin scaffold. In the same differentiation medium, a high-stiffness NF-gelatin facilitated DPSC differentiation to form a mineralized tissue, while a low-stiffness NF-gelatin promoted a soft pulp-like tissue formation from the DPSCs. A facile method was then developed to integrate the low- and high-stiffness gelatin matrices into a single scaffold (S-scaffold) for pulpodentin complex regeneration. A 4-week in vitro experiment showed that biomineralization took place only in the high-stiffness peripheral area and formed a ring-like structure surrounding the non-mineralized central area of the DPSC/S-scaffold construct. A complete pulpodentin complex similar to natural pulpodentin was successfully regenerated after subcutaneous implantation of the DPSC/S-scaffold in nude mice for 4 weeks. Histological staining showed a significant amount of extracellular matrix (ECM) formation in the newly formed pulpodentin complex, and a number of blood vessels were observed in the pulp tissue. Taken together, this work shows that modulating the stiffness of the NF-gelatin scaffold is a successful approach to regenerating a complete tooth-like pulpodentin complex. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.