Wang Lei, Fu Hui, Wang Wenwen, Liu Yi, Li Xumin, Yang Jijing, Li Lingli, Wu Gang, Pan Yihuai
Institute of Stomatology, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang325027, China; Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and VrijeUniversiteit Amsterdam (VU), 1081 LA, Amsterdam, the Netherlands; Wenzhou Institute of Biomaterials & Engineering, University of Chinese Academy of Science, Wenzhou, Zhejiang325027, China.
Institute of Stomatology, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang325027, China.
Acta Biomater. 2021 Mar 1;122:160-171. doi: 10.1016/j.actbio.2020.12.031. Epub 2020 Dec 26.
Pulp-capping materials are commonly adopted in the clinic to form reparative dentin and thus protect dental pulp tissues from cases of deep caries, accidentally exposed pulps or partial pulpotomy. Some traditional pulp capping materials used in the clinic include calcium hydroxide and mineral trioxide aggregates. However, there are limitations to thin restorative dentin, and a long period of time is needed to cause degenerative changes in dental pulp. In this paper, injectable colloidal gels were developed to induce the formation of reparative dentin through a simple UV method from methacrylic acid functionalized gelatin loaded with notoginsenoside R1 (Gel-MA/NGR1). The results of the physicochemical property examinations showed that the prepared Gel-MA/NGR1 hydrogel possessed an appropriate interconnected porous microarchitecture with a pore size of 10.5 micrometres and suitable mechanical properties with a modulus of 50-60 kPa, enabling cell adhesion and proliferation. The hydrogel remained hydrophilic with sustained drug release performance. In addition, Gel-MA/NGR1 significantly enhanced the odontogenetic differentiation of mouse dental papilla cells by elevating the expression levels of the dentinogenic markers ALP and OCN and extracellular matrix mineralization. In vivo stimulation was carried out by injecting the precursors into the predrilled alveolar cavity of Sprague-Dawley rats followed by immediate in situ UV crosslinking. The results showed that Gel-MA/NGR1 has a strong capacity to promote reparative dentin formation. Haematoxylin& eosin, Masson, and immunohistochemical staining (DMP-1, DSPP, OCN and RUNX2) and micro-CT were employed to illustrate the effectiveness of dentinogenesis, and the relative volumes of calcification were found to have increased ~175-fold. All of the results showed that the Gel-MA/NGR1 hydrogel promoted reparative dentin formation, which suggests that this hydrogel provides great potential as a pulp-capping material to induce dentin formation.
临床中通常采用盖髓材料来形成修复性牙本质，从而保护牙髓组织免受深龋、意外露髓或部分牙髓切断术等情况的影响。临床中使用的一些传统盖髓材料包括氢氧化钙和矿物三氧化物凝聚体。然而，修复性牙本质较薄存在局限性，并且需要较长时间才能引起牙髓的退行性变化。在本文中，通过一种简单的紫外线方法，从负载三七皂苷R1的甲基丙烯酸功能化明胶（Gel-MA/NGR1）中开发出可注射胶体凝胶，以诱导修复性牙本质的形成。物理化学性质检查结果表明，制备的Gel-MA/NGR1水凝胶具有合适的相互连通的多孔微结构，孔径为10.5微米，具有合适的力学性能，模量为50-60 kPa，能够实现细胞黏附和增殖。该水凝胶保持亲水性并具有持续的药物释放性能。此外，Gel-MA/NGR1通过提高牙本质生成标志物碱性磷酸酶（ALP）和骨钙素（OCN）的表达水平以及细胞外基质矿化，显著增强了小鼠牙乳头细胞的成牙分化。通过将前体注射到Sprague-Dawley大鼠预先钻好的牙槽腔中，然后立即进行原位紫外线交联来进行体内刺激。结果表明，Gel-MA/NGR1具有很强的促进修复性牙本质形成的能力。采用苏木精-伊红染色、Masson染色和免疫组织化学染色（牙本质基质蛋白-1、牙本质涎磷蛋白、骨钙素和RUNX2）以及显微CT来说明牙本质生成的有效性，发现钙化的相对体积增加了约175倍。所有结果表明，Gel-MA/NGR1水凝胶促进了修复性牙本质的形成，这表明这种水凝胶作为一种诱导牙本质形成的盖髓材料具有巨大潜力。
