牙髓-牙本质复合体再生的影响因素及其生物学策略  

Influencing factors of pulp-dentin complex regeneration and related biological strategies

作　　者：邹杰林 毛靖[1,2,3] 石鑫 ZOU Jielin;MAO Jing;SHI Xin(Center of Stomatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;School of Stomatology,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属同济医院口腔医学中心,湖北武汉430030 [2]华中科技大学同济医学院口腔医学院,湖北武汉430030 [3]口腔颌面发育与再生湖北省重点实验室,湖北武汉430022

出　　处：《浙江大学学报（医学版）》2022年第3期350-361,共12页Journal of Zhejiang University(Medical Sciences)

基　　金：中华口腔医学会中西部口腔正畸临床研究项目(CSA-MW02021-03);口腔颌面发育与再生湖北省重点实验室开放基金(2020kqhm002)。

摘　　要：再生性牙髓治疗利用组织工程方法修复缺损牙本质和牙髓组织,再生具有正常生理功能的牙髓-牙本质复合体,以期恢复牙髓的血管神经化和免疫功能并重建管样牙本质。显著影响再生性牙髓治疗效能的因素包括干细胞、生物信号分子和生物支架材料。根据是否来自牙源性组织,干细胞可分为牙源性干细胞(如牙髓干细胞)和非牙源性干细胞(如骨髓间充质干细胞)。鉴于干细胞具有倾向分化为其原始来源组织的特性,牙源性干细胞在再生性牙髓治疗中展现出一定优势。联合应用多种信号分子并通过激活信号转导通路如Wnt/β-catenin、BMP/Smad,对改善干细胞迁移、增殖、成牙本质细胞分化和血管神经再生潜能发挥关键作用。适用于再生性牙髓治疗的生物支架材料包括自然来源材料和人工合成材料,人工合成材料应模仿天然组织进行生物仿生修饰,以营造适宜的再生微环境并实现对信号转导通路的时空调控。牙髓-牙本质复合体再生的真正实现有赖于干细胞移植和干细胞归巢两大策略。干细胞归巢策略因可避免干细胞的体外分离和培养而在临床操作上更具优势,但如何提高干细胞归巢成功率并促进其增殖和分化以实现牙髓-牙本质复合体真正再生仍有待解决。本文介绍了诱导牙髓-牙本质复合体再生的影响因素,探讨其科学、可行的生物学策略,并展望再生性牙髓治疗未来的研究方向,以期为再生性牙髓治疗临床转化和推广应用提供参考。Regenerative endodontic therapy(RET)utilizing tissue engineering approach can promote the regeneration of pulp-dentin complex to restore pulp vascularization,neuralization,immune function and tubular dentin,therefore the regenerated pulp-dentin complex will have normal function.Multiple factors may significantly affect the efficacy of RET,including stem cells,biosignaling molecules and biomaterial scaffolds.Stem cells derived from dental tissues(such as dental pulp stem cells)exhibit certain advantages in RET.Combined application of multiple signaling molecules and activation of signal transduction pathways such as Wnt/β-catenin and BMP/Smad play pivotal roles in enhancing the potential of stem cell migration,proliferation,odontoblastic differentiation,and nerve and blood vessel regeneration.Biomaterials suitable for RET include naturally-derived materials and artificially synthetic materials.Artificially synthetic materials should imitate natural tissues for biomimetic modification in order to realize the temporal and spatial regulation of pulpdentin complex regeneration.The realization of pulp-dentin complex regeneration depends on two strategies:stem cell transplantation and stem cell homing.Stem cell homing strategy does not require the isolation and culture of stem cells in vitro,so is better for clinical application.However,in order to achieve the true regeneration of pulp-dentin complex,problems related to improving the success rate of stem cell homing and promoting their proliferation and differentiation need to be solved.This article reviews the influencing factors of pulp-dentin complex regeneration and related biological strategies,and discusses the future research direction of RET,to provide reference for clinical translation and application of RET.

关 键 词：牙髓-牙本质复合体再生 干细胞 生物信号分子 生物支架材料 细胞移植 细胞归巢 综述 

分 类 号：R318[医药卫生—生物医学工程] R781[医药卫生—基础医学]