基于载SDF-1水凝胶微孔道系统构建血管化牙髓组织的研究

Dental pulp disease is a non-infectious disease with high incidence. Traditional root canal treatment will render teeth losing the blood and nutrition supply, which makes teeth brittle and leads to tooth fracture. Regenerative endodontic procedure aims to preserve pulp vitality, inducing the formation of pulp-liked tissue to replace the infected pulp. However, the adult dental pulp merely connects with the body through a quite narrow apical foramen, which makes the treatment with simple cell transplantation easily to fail due to a lack of blood supply and nutrition support. In that case, necrosis at an early stage may occur, followed by the failure of the regenerative therapy. The present project uses stem cells from apical papilla as seeding cells, and adopts the method of 3D bioprinting to build a microchannel system in hydrogel scaffold, aiming to improve the efficiency of the nutrient exchange in the scaffold. At the same time, by adding exogenous growth factor SDF-1, we plan to promote cell migration and the differentiation towards vascularization in the dental pulp regeneration process. Through the above-mentioned strategy, we may promote vascularization in the early stage of dental pulp tissue reconstruction, and improve the outcome of pulp regeneration. Besides, this may provide reference for the vascularization of other larger tissue.

牙髓病是发病率最高的非传染性疾病之一，传统的根管治疗使牙齿失去牙髓的血供和营养，易导致牙体变脆而发生牙折。再生性牙髓治疗目的是保存活髓，诱导牙髓样组织形成以替代感染的牙髓，然而成体牙髓组织仅通过狭小的根尖孔与机体相连，使得单纯的细胞移植易因血供和营养支持不佳，导致再生治疗的预后较差。本项目以根尖牙乳头细胞作为牙髓再生种子细胞，采用3D生物打印的方法在水凝胶支架中设计微孔道系统，通过预先构建的微孔道来提高支架材料内部营养物质交换的效率；同时，通过加入外源性生长因子SDF-1促进牙髓再生过程中的细胞迁移和血管向分化，以促进牙髓组织重建中的早期血管化。通过以上策略，有望改善再生牙髓组织的转归，实现血管化牙髓组织的再生，并可为其他大块组织的血管化提供可能参考策略。

牙髓病是发病率最高的非传染性疾病之一，传统的根管治疗使牙齿失去牙髓的血供和营养，易导致牙体变脆而发生牙折。再生性牙髓治疗目的是保存活髓，诱导牙髓样组织形成以替代感染的牙髓，然而成体牙髓组织仅通过狭小的根尖孔与机体相连，使得单纯的细胞移植易因血供和营养支持不佳，导致再生治疗的预后较差。本项目针对牙髓疾病的传统清创式治疗及目前再生性牙髓治疗血管化不足的弊端，提出一种创新式的解决方案。利用3D打印的GelMA水凝胶构建微孔道系统，为再生性牙髓治疗初期提供营养和支持，同时，为了提高再生牙髓中的血管化重建效果，在微孔道系统中加载了牙髓组织来源的外泌体，其加入可促进局部细胞的迁移与血管向分化，从而达到重建血管化牙髓组织的目的。