基于生物打印技术研制生物活性可降解牙周缺损修复材料

More than 80% adults in China suffer from the periodontal disease with varying degrees. Periodontal disease can result in periodontal defects, which leads to alveolar bone destruction. Hence, repair of periodontal defects is an urgent problem to be deal with in the field of periodontal disease treatment, which has an important academic value and social significance. At present, the design of periodontal defects repair materials (PDRM) is originated from the traditional method of bone repair, which is unable to fully meet the clinical requirements for periodontal defects repair. In this project, bio-printing technology and method of tissue engineering were employed to develop a kind of biomedical material dedicated to repairing periodontal defects based on the evaluation of stem cells differentiation. First of all, two kinds of the photo-crosslinking macromolecules were used to prepare hydrogel, and then the optimal material composition of the hydrogel was selected by charactering the biocompatibility and degradability. Secondly, the effect of several PDRM based on pearl water soluble matrix, in-vitro mineralized calcium phosphate and the photo-crosslinking hydrogel on human gingival mesenchymal stem cells differentiation to osteoblasts was investigated by the bio-printing platform. At last, dog periodontal disease model was built to evaluate the in-vivo repair ability of PDRM. Tissue engineering and bio-printing technology were combined in this project to discuss a novel method to investigate the cell/material interaction, develop a new material for repairing periodontal defects and lay the foundation for its clinical application.

我国80%以上成年人患有不同程度的牙周病，它会引发牙周组织缺损，破坏牙槽骨。因此，修复牙周缺损是治疗牙周病亟待解决的问题，具有重要的学术价值和社会意义。目前，国内外针对牙周缺损修复材料（PDRM）的设计均源于传统的骨修复，无法完全满足缺损修复的临床需求。项目拟用生物打印技术，基于PDRM诱导干细胞定向分化的评价，研制专用于牙周缺损修复的生物材料。首先，拟采用两种具有光交联特性的材料制备水凝胶并通过表征其生物相容性及降解性，筛选最佳材料组成。其次，利用生物打印平台研究基于珍珠水溶性有机质、原位矿化磷酸钙盐及光交联水凝胶构成的几种PDRM对人牙龈间充质干细胞成骨分化的作用，探讨材料特性对干细胞分化的影响。最后，建立犬牙周病模型并评价PDRM的体内修复能力。该项目将组织工程与生物打印技术相结合，探讨一种全新的细胞/材料相互作用的研究方法，并研制新型PDRM，以期为牙周缺损修复的临床应用奠定基础。

我国80%以上成年人患有不同程度的牙周疾病。重度牙周疾病会导致牙齿支持组织破坏，直至牙齿脱落。治疗重度牙周疾病的关键在于修复已经破坏的牙槽骨。天然大分子和合成高分子均是常见的生物材料，而因其各自的缺点在一定程度上限制了它们单独用于开发医用生物材料。因此，需要结合两种材料的优势，开发复合生物材料用于缺损修复。目前，单独设计生物材料组成并采用传统的材料混合的方法筛选理想的复合材料组成非常耗时。同时，针对生物材料与干细胞相互作用的研究大部分基于体外二维模型，很难与在体三维细胞微环境相关联。因此，本研究利用自行开发的生物打印平台高通量的优势，通过控制两种水凝胶生物材料（天然大分子GelMA和合成高分子PEG）的打印体积比例，提出一种基于生物打印的策略高通量地制备具有材料组成梯度的GelMA/PEG复合水凝胶牙周缺损修复材料。首先，在三维环境下，研究了复合水凝胶材料组成对牙周膜干细胞行为及命运的调控作用，并筛选出具有4/1材料组成的GelMA/PEG复合水凝胶为最优材料组成。随后，将负载牙周膜干细胞、具有4/1材料组成的GelMA/PEG复合水凝胶注射入大鼠牙槽骨缺损模型。体内研究结果显示这种具有最优材料组成的复合水凝胶包裹牙周膜干细胞表现出最优异的新骨生成能力。本研究基于生物打印的策略不仅有助于筛选用于模拟牙周膜干细胞外基质的水凝胶材料组成，进而开发牙周缺损修复材料，而且适用于其他细胞—生物材料相互作用研究，并促进功能性组织再生。