Li Xiaochan, Heng Boon Chin, Bai Yunyang, Wang Qianqian, Gao Min, He Ying, Zhang Xinwen, Deng Xuliang, Zhang Xuehui
Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
Bioact Mater. 2022 May 21;20:81-92. doi: 10.1016/j.bioactmat.2022.05.007. eCollection 2023 Feb.
Stem cells from human exfoliated deciduous teeth (SHED) uniquely exhibit high proliferative and neurogenic potential. Charged biomaterials have been demonstrated to promote neural differentiation of stem cells, but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated. Here, by utilizing different annealing temperatures prior to corona poling treatment, BaTiO/P(VDF-TrFE) ferroelectric nanocomposite membranes with varying charge polarization intensity ( ≈ 0, 4, 12 and 19 pC N) were fabricated. Enhanced expression of neural markers, increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation. Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx, focal adhesion formation, FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge. Hence, this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.
人脱落乳牙干细胞(SHED)独特地表现出高增殖和神经生成潜力。带电生物材料已被证明可促进干细胞的神经分化,但这些材料的电刺激对SHED神经分化的剂量反应效应仍有待阐明。在此,通过在电晕极化处理之前利用不同的退火温度,制备了具有不同电荷极化强度(≈0、4、12和19 pC N)的BaTiO/P(VDF-TrFE)铁电纳米复合膜。随着纳米复合膜表面电荷增加,观察到神经标志物表达增强、细胞伸长增加以及更显著的神经突生长,表明表面电荷对SHED神经分化具有剂量反应效应。对潜在分子机制的进一步研究表明,细胞内钙内流、粘着斑形成、FAK-ERK机械传感途径和神经生成相关的ErbB信号通路与表面电荷增强SHED神经分化有关。因此,本研究证实了生物材料表面电荷对SHED神经分化的剂量反应效应,并为所涉及的分子机制和信号通路提供了初步见解。