Xenogeneic dentin matrix as a scaffold for biomineralization and induced odontogenesis
Xenogeneic dentin matrix as a scaffold for biomineralization and induced odontogenesis
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异种牙本质基质作为生物矿化和诱导牙发育的支架
DOI：
10.1088/1748-605x/abfbbe
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发表时间：
2021-07-01
影响因子：
4
通讯作者：
Yu, Riyue
中科院分区：
文献类型：
--
作者：
Li, Hui;Ma, Bo;Yu, Riyue
基于异种细胞外基质的再生医学的公认机制包括及时降解、释放生物活性分子、诱导干细胞分化和良好控制炎症。该过程对于基质组织重建是最可行的，但不适用于不可降解的支架和预制形状的组织再生，如牙形成。经处理的牙本质基质（TDM）已被确定为牙本质再生的生物活性支架。本研究旨在探讨异种猪TDM（pTDM）诱导牙胚发育的可行性。比较pTDM与人TDM（hTDM）的生物学特性。为研究其在炎症微环境中对同种异体牙囊细胞（DFC）的生物诱导能力，将人DFC转染的pTDM与人外周血单个核细胞（hPBMC）共培养，并将大鼠DFC转染的pTDM移植到大鼠皮下模型。结果表明，pTDM具有与hTDM相似的矿物相和生物活性分子。hDFCs在pTDM和hTDM的诱导下表达相似的col-I、骨桥蛋白和碱性磷酸酶（ALP）（均由成牙本质细胞表达）。而与hPBMC共培养后，col-I、牙本质基质蛋白-1（dentinmatrixprotein-1，DNT-1）和骨唾液酸蛋白（bonesialoprotein，BSP）的表达下调。异种移植物在体内不可避免地引发Th1炎症（上调CD8、TNF-α、IL-1 β等）。但牙本质和牙骨质的生物矿化仍在进行，胶原纤维、成牙本质细胞样细胞、成纤维细胞参与牙本质的形成。虽然在3周时部分吸收，但种植体阳性表达牙发生相关蛋白，如col-I和p53 - 1。总之，异种TDM保存了将同种异体DFC引入牙向分化的超微结构和分子，并促进体内牙发生和生物矿化。然而有效的免疫调节方法值得进一步探索。
Commonly recognized mechanisms of the xenogeneic-extracellular matrix-based regenerative medicine include timely degradation, release of bioactive molecules, induced differentiation of stem cells, and well-controlled inflammation. This process is most feasible for stromal tissue reconstruction, yet unsuitable for non-degradable scaffold and prefabricated-shaped tissue regeneration, like odontogenesis. Treated dentin matrix (TDM) has been identified as a bioactive scaffold for dentin regeneration. This study explored xenogeneic porcine TDM (pTDM) for induced odontogenesis. The biological characteristics of pTDM were compared with human TDM (hTDM). To investigate its bioinductive capacities on allogeneic dental follicle cells (DFCs) in the inflammation microenvironment, pTDM populated with human DFCs were co-cultured with human peripheral blood mononuclear cells (hPBMCs), and pTDM populated with rat DFCs were transplanted into rat subcutaneous model. The results showed pTDM possessed similar mineral phases and bioactive molecules with hTDM. hDFCs, under the induction of pTDM and hTDM, expressed similar col-I, osteopontin and alkaline phosphatase (ALP) (all expressed by odontoblasts). Whereas, the expression of col-I, dentin matrix protein-1 (DMP-1) and bone sialoprotein (BSP) were down-regulated when cocultured with hPBMCs. The xenogeneic implants inevitably initiated Th1 inflammation (up-regulated CD8, TNF-α, IL-1β, etc) in vivo. However, the biomineralization of pre-dentin and cementum were still processed, and collagen fibrils, odontoblast-like cells, fibroblasts contributed to odontogenesis. Although partially absorbed at 3 weeks, the implants were positively expressed odontogenesis-related-proteins like col-I and DMP-1. Taken together, xenogeneic TDM conserved ultrastructure and molecules for introducing allogeneic DFCs to odontogenic differentiation, and promoting odontogenesis and biomineralization in vivo. Yet effective immunomodulation methods warrant further explorations.