Rajasekar Vidhyashree, Abdalla Mohamed Mahmoud, Neelakantan Prasanna, Yiu Cynthia K Y
Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, Hong Kong.
Dental Biomaterials, Faculty of Dental Medicine Al-Azhar University, Cairo, Egypt.
Int Endod J. 2025 Sep;58(9):1354-1383. doi: 10.1111/iej.14261. Epub 2025 Jun 9.
Bioactive molecules have gained significant attention in regenerative medicine due to their ability to boost the reparative properties of stem cells, including those in the dental pulp. This narrative review aims to deepen our understanding of the dynamics of bioactive molecules in the dental pulp and their role in enhancing hard tissue reparative processes.
(i) To discuss the role of different cells and the critical pathways involved in dentine formation through direct (reparative) or indirect (infection control and immunomodulatory) mechanisms. (ii) To highlight how innovative therapeutic strategies could be employed to target key molecules for successful dentine repair and regeneration.
The review encompassed all years up to the search period. Databases such as PubMed, Scopus and Medline were utilized to gather relevant studies. The search strategy involved specific signalling molecules such as Transforming growth factor-β1 (TGF-β), Bone Morphogenetic Proteins (BMP), Small Integrin Binding Ligand N-linked Glycoproteins (SIBLING) and growth factors. Cell types including odontoblasts, fibroblasts, immune cells and dental pulp stem cells (DPSCs) were of interest. Additionally, signalling pathways like Wnt, Notch, Shh, amongst others, were investigated for their roles in repair mechanisms. Key terms were combined using Boolean operators [Cell type] AND [signalling molecules] AND/OR [dentine], [Cell type] AND/OR [signalling pathways] AND/OR [dentine] to include studies addressing the interaction of these components in enhancing repair processes.
Key molecules such as TGF-β1, BMP and SIBLING proteins effectively enhance the dentine reparative response, whilst other molecules such as complement proteins and antimicrobial peptides primarily activate immune cells and facilitate pathogen clearance to promote the regenerative capabilities of DPSCs. This well-orchestrated interaction emphasizes the need to investigate the effects of these molecules on all cells within the dental pulp. Morphogenic signalling molecules such as BMP-2, -4 and -7, and Wnt show temporal, yet significant regenerative properties, whilst Shh and Notch present inconsistent effects on dentine regeneration, and a consensus on their roles and properties in dentine repair has yet to be reached.
This review highlights the critical role of bioactive molecules in dentine repair to guide the development of next-generation bioinspired therapeutics for vital pulp therapy.
生物活性分子因其能够增强干细胞(包括牙髓干细胞)的修复特性,在再生医学中受到了广泛关注。本叙述性综述旨在加深我们对牙髓中生物活性分子动态及其在增强硬组织修复过程中作用的理解。
(i)讨论不同细胞的作用以及通过直接(修复)或间接(感染控制和免疫调节)机制参与牙本质形成的关键途径。(ii)强调如何采用创新治疗策略来靶向关键分子以实现成功的牙本质修复和再生。
该综述涵盖了截至检索期的所有年份。利用PubMed、Scopus和Medline等数据库收集相关研究。检索策略涉及特定的信号分子,如转化生长因子-β1(TGF-β)、骨形态发生蛋白(BMP)、小整合素结合配体N-连接糖蛋白(SIBLING)和生长因子。感兴趣的细胞类型包括成牙本质细胞、成纤维细胞、免疫细胞和牙髓干细胞(DPSC)。此外,还研究了Wnt、Notch、Shh等信号通路在修复机制中的作用。使用布尔运算符[细胞类型] AND [信号分子] AND/OR [牙本质]、[细胞类型] AND/OR [信号通路] AND/OR [牙本质]组合关键词,以纳入涉及这些成分在增强修复过程中相互作用的研究。
TGF-β1、BMP和SIBLING蛋白等关键分子可有效增强牙本质修复反应,而补体蛋白和抗菌肽等其他分子主要激活免疫细胞并促进病原体清除,以提高DPSC的再生能力。这种精心协调的相互作用强调了研究这些分子对牙髓内所有细胞影响的必要性。BMP-2、-4和-7以及Wnt等形态发生信号分子表现出暂时但显著的再生特性,而Shh和Notch对牙本质再生的影响不一致,关于它们在牙本质修复中的作用和特性尚未达成共识。
本综述强调了生物活性分子在牙本质修复中的关键作用,以指导下一代生物启发疗法用于牙髓活力治疗的开发。