三维打印抗炎生物支架调控Wnt/β-catenin 信号通路促进牙周组织再生

Periodontal regeneration is a specialized regenerative process for soft and hard tissues (including alveolar bone, cementum and periodontal ligament) that surround and support the tooth. It is a highly regulated process controlled by a complex network of cell signalling pathways. Our previous studies have shown that the Wnt/β-catenin signalling pathway can be activated by local injection of lithium chloride (LiCl), further regulating the biological function of the periodontal ligament cells and promoting osteogenesis and cementogenesis. Taken into account that periodontitis is an inflammatory disease of the periodontium caused by multiple periodontal pathogens, the new generation of bioactive scaffolds should possess not only complex structures to facilitate the regeneration of periodontium but also antibacterial and immunoregulatory properties to create an optimal microenvironment. The purpose of this study is to use advanced 3D printing technique to develop multifunctional bioactive scaffolds with macroporous and microtubule structures, which can activate the Wnt/β-catenin signalling pathway through the controlled release of lithium (Li) ions in the microenvironment, inhibit bacterial growth and regulate immune response, thereby promoting the reconstruction of alveolar bone and cementum to achieve the ultimate goal of periodontal tissue regeneration.

牙周再生是一个高度特化的牙齿支持组织（包括牙槽骨、牙骨质和牙周膜）重建过程，需要一系列信号分子网络的调控，目前仍是医学界的难题。我们的前期研究表明，通过局部注射氯化锂（LiCl）试剂，可以激活Wnt/β-catenin信号通路，调控牙周膜细胞的生物学功能，促使成骨及成牙骨质分化。考虑到牙周炎是由多种牙周致病菌协同引起的炎症破坏性疾病，新型生物支架除具备复杂结构促使牙周组织重建外，还应具备抑菌以及调控免疫反应的性能。本课题拟在前期研究基础上，采用三维打印技术制备具有联通大孔结构以及微管结构的生物活性支架，通过可控释放微量营养元素锂离子（Li）激活Wnt/β-catenin信号通路，调控微环境，诱导牙周膜细胞成骨/成牙骨质分化，抑制牙周致病菌生长，以及调控巨噬细胞免疫应答，从而达到修复牙周组织复杂结构的目的。

牙周病治疗的最终目的是停止疾病的病程，促进被炎症破坏和吸收的软硬组织的重建，从而实现牙周组织的再生。本研究不仅旨在探讨惨锂生物活性玻璃(Li-BGS)对人类牙周膜干细胞的成骨、成牙骨质和牙周组织再生的影响以及相应的机制,而且同时探讨Li-BGS培养后PDLCs的成骨/成骨分化能力及RAW 264.7细胞在炎症环境下的抗炎作用。同时，我们进一步研究了Wnt/β-catenin信号通路在这一过程中的参与机制。体内实验中，比较Li-BGS和BGS粉末对大鼠牙槽骨缺损再生的影响。结果表明，Li-BGS浸提液对RAW 264.7细胞具有抗炎作用。此外，我们观察到一定浓度的Li-BGS浸提液通过激活Wnt/β-catenin信号通路，不仅可以显著促进PDLCs的直接成骨/成骨分化，还可以调节有利的炎症微环境、巨噬细胞极化，从而间接促进牙周组织再生。体内实验结果表明，在大鼠牙周缺损模型中，与BGS相比，Li-BGS可显著促进骨缺损和牙周缺损的再生。.因此，Li-BGS被认为是一种很有前途的牙周组织再生生物活性材料，从而为牙周炎相关疾病的治疗提供了一种很有前途的策略。