Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People's Republic of China.
Department of Chemistry, Northeast Normal University, Changchun, 130024, People's Republic of China.
Int J Nanomedicine. 2024 Jul 3;19:6659-6676. doi: 10.2147/IJN.S464871. eCollection 2024.
Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue.
The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining.
In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin.
The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.
活髓治疗（VPT）被认为是一种保存龋病和外伤引起的牙髓炎中牙髓活力的保守治疗方法。然而，作为最常用的修复材料，矿物三氧化物聚合体（MTA）在炎症条件下疗效有限。本研究介绍了一种创新的纳米复合水凝胶，旨在同时靶向抗炎和牙本质矿化，以有效保存活髓组织。
通过将 L-（CaP-ZnP）/SA 纳米复合水凝胶与海藻酸钠（SA）相结合，设计了 L-（CaP-ZnP）/SA 纳米复合水凝胶，并用 TEM、SEM、FTIR、EDX、ICP-AES 和 Zeta 电位进行了表征。体外评估了细胞毒性和抗炎特性。用人牙髓干细胞（hDPSCs）培养物用脂多糖（LPS）诱导炎症反应，通过碱性磷酸酶（ALP）/茜素红 S（ARS）染色、qRT-PCR、免疫荧光染色和 Western blot 分别测量细胞成牙本质分化并探讨可能的信号通路。体内利用牙髓炎模型，通过苏木精和伊红（HE）染色和免疫组织化学染色，探讨 L-（CaP-ZnP）/SA 纳米复合水凝胶在控制牙髓炎症和增强牙本质矿化方面的潜力。
体外实验表明成功合成了纳米复合水凝胶，具有良好的生物相容性。在炎症条件下，与 MTA 相比，L-（CaP-ZnP）/SA 纳米复合水凝胶表现出更好的抗炎和成牙本质作用。此外，纳米复合水凝胶显著增加了 p38 磷酸化，提示 p38 信号通路参与牙髓修复。重要的是，在大鼠牙髓炎模型中，L-（CaP-ZnP）/SA 纳米复合水凝胶下调炎症标志物，同时上调矿化相关标志物，从而刺激形成强健的修复性牙本质。
具有良好生物相容性的 L-（CaP-ZnP）/SA 纳米复合水凝胶通过激活 p38 信号通路有效促进炎症消退和增强牙本质矿化，作为盖髓材料，为治疗牙髓炎提供了一种有前景的先进解决方案。
