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Magnesium-Based Resorbable Biomaterials: Biological Effects to Clinical Use. 镁基可吸收生物材料:临床应用的生物学效应。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251368274
N Lacin,C Sfeir
Magnesium (Mg) has emerged as a promising biomaterial, drawing significant attention for its potential in biomedical applications. As Mg-based products are in several clinical trials and in clinical use, it is timely to summarize the current knowledge of the biological effects and clinical potential with a special emphasis on oral and craniomaxillofacial applications. Mg-based biomaterials offer biocompatibility, biodegradability, and mechanical properties suitable for various clinical applications. These characteristics make them promising alternatives to polymers and permanent metals used in implantable devices, meshes, and fixation plates, effectively addressing challenges such as stress shielding, inflammation, and the need for removal surgeries. Their degradation enables gradual native tissue replacement while providing initial support, which is why most of the devices were developed for bone fixation applications. Clinically, Mg-based biomaterials such as resorbable membranes and bone grafts show potential in guided bone/tissue regeneration. In the United States, there is one FDA-approved Mg-based device for orthopedic applications compared with more regulatory approvals in Europe and Asia (at the time of writing). The main limitations that have delayed their widespread clinical use are the variable site-dependent degradation of Mg and Mg's effect as a biological agent, which adds another layer to the regulatory process. Studies show Mg's pro-osteogenic, anti-osteoclastic, and anti-inflammatory properties. Mg enhances bone regeneration by activating signaling pathways in mesenchymal stem cells and modulating the immune response. As research progresses, innovative Mg delivery systems leveraging its biological properties may utilize the potential of Mg-based biomaterials for advancing regenerative therapies. This review explores the following: (1) the current status of Mg-based biomaterials in clinical applications, (2) the corrosion properties of Mg metal devices and the biological interactions of degradation by-products, (3) the biological and immunomodulatory role of Mg in bone regeneration, and (4) the use of Mg-based biomaterials in oral and maxillofacial bone regeneration.
镁(Mg)作为一种很有前途的生物材料,其在生物医学领域的应用潜力引起了人们的广泛关注。由于镁基产品正在进行多项临床试验和临床应用,因此总结目前对其生物学效应和临床潜力的了解是及时的,并特别强调口服和颅颌面应用。镁基生物材料具有生物相容性、生物可降解性和适合各种临床应用的机械性能。这些特性使其有望替代聚合物和永久性金属用于植入式装置、网片和固定板,有效地解决诸如应力屏蔽、炎症和移除手术的需求等挑战。它们的降解可以在提供初始支持的同时逐渐替代原生组织,这就是为什么大多数设备都是为骨固定应用而开发的。临床上,镁基生物材料如可吸收膜和骨移植物在引导骨/组织再生中显示出潜力。在美国,有一种fda批准的基于mg的器械用于骨科应用,相比之下,欧洲和亚洲的监管部门批准更多(在撰写本文时)。延迟其广泛临床应用的主要限制是Mg的可变位点依赖性降解和Mg作为生物制剂的作用,这为监管过程增加了另一层。研究表明镁具有促骨、抗破骨和抗炎的特性。镁通过激活间充质干细胞的信号通路和调节免疫反应来促进骨再生。随着研究的进展,利用其生物学特性的创新型镁递送系统可能会利用镁基生物材料的潜力来推进再生治疗。本文就以下方面进行了综述:(1)镁基生物材料的临床应用现状;(2)镁金属器件的腐蚀特性及其降解副产物的生物相互作用;(3)镁在骨再生中的生物和免疫调节作用;(4)镁基生物材料在口腔颌面骨再生中的应用。
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引用次数: 0
Mir-27 Promotes Periodontal Regeneration via Osteogenesis/Angiogenesis. Mir-27通过成骨/血管生成促进牙周再生。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251366279
Y Ding,J Luan,H S Malmstrom,X Luan,T G H Diekwisch
The interplay between osteogenesis and angiogenesis is an important prerequisite for successful bone regeneration as it provides capillary supply to the initial bone lamellae involved in skeletogenesis. The Wnt signaling pathway is one of the key signaling pathways promoting both osteogenesis and angiogenesis. In the present study, we evaluated the regenerative potential of microRNA-27 (miR-27) by delivering miR-27 mimic via lipid nanoparticles (LNPs) to enhance periodontal tissue repair through the targeted modulation of Secreted Frizzled-Related Protein 1 (SFRP1). Our study demonstrated that inflammatory conditions inhibit the expression and function of miR-27 in a periodontitis model. miR-27 treatment significantly upregulated key modulators of periodontal regeneration, including osteogenic markers (ALP, RUNX2, and COL1) and angiogenic factors (CD31, CD34, and VEGF). This treatment also resulted in increased alkaline phosphatase activity and enhanced mineral deposition, alongside improved spheroid sprouting and tube formation in Matrigel cultures. LNPs were applied to optimize miR-27 delivery for efficient transfection. In vivo implantation revealed that miR-27 accelerated extracellular matrix remodeling in subcutaneous implants, induced a 6-fold increase in neovascularization, and significantly enhanced periodontal tissue formation and bone regeneration, as evidenced by a 43.9% reduction in the distance between the alveolar bone ridge and the cementoenamel junction. Mechanistically, miR-27 promoted osteogenic and angiogenic responses by suppressing SFRP1, a known Wnt signaling inhibitor and validated target of miR-27, thereby activating the Wnt pathway. Together, these studies demonstrate that miR-27 mimic functioned as a bioactive molecule promoting periodontal tissue regeneration through angiogenesis coinciding with osteogenesis. Our study also suggests that the miR-27-LNPs/scaffold combination is an exciting novel agent for the treatment of periodontal disease.
骨生成和血管生成之间的相互作用是骨再生成功的重要前提,因为它为参与骨生成的初始骨片提供了毛细血管供应。Wnt信号通路是促进骨生成和血管生成的关键信号通路之一。在本研究中,我们通过脂质纳米颗粒(LNPs)递送miR-27模拟物,通过靶向调节分泌卷曲相关蛋白1 (SFRP1)来增强牙周组织修复,从而评估了microRNA-27 (miR-27)的再生潜力。我们的研究表明,炎症条件抑制了牙周炎模型中miR-27的表达和功能。miR-27处理显著上调牙周再生的关键调节因子,包括成骨标志物(ALP、RUNX2和COL1)和血管生成因子(CD31、CD34和VEGF)。该处理还增加了碱性磷酸酶活性,增强了矿物质沉积,同时改善了基质培养中的球形发芽和管状形成。LNPs用于优化miR-27的传递,以实现高效转染。体内植入实验表明,miR-27加速了皮下种植体的细胞外基质重塑,诱导新生血管增加6倍,并显著促进牙周组织形成和骨再生,牙槽骨嵴与牙釉质交界处之间的距离减少43.9%。在机制上,miR-27通过抑制已知的Wnt信号抑制剂SFRP1促进成骨和血管生成反应,从而激活Wnt通路。总之,这些研究表明,miR-27模拟物作为一种生物活性分子,通过血管生成和成骨作用促进牙周组织再生。我们的研究还表明,miR-27-LNPs/支架组合是一种令人兴奋的治疗牙周病的新药物。
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引用次数: 0
Cationic Polymer for Aligner and Oral Biofilm Removal via Osmotic Mechanism. 阳离子聚合物对口腔生物膜的渗透去除作用。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251368263
K Seo,J Moon,R Bhat,U Mangal,S-H Choi,J-S Kwon
Dental caries caused by cariogenic biofilms is a significant challenge in modern dentistry, especially with aligner treatments, where biofilms can easily build up during prolonged use and lead to serious risks. Traditional antimicrobial methods focus on bacterial killing and often overlook the vital task of removing the biofilm matrix, allowing the quick reattachment of bacteria. In this study, we introduce an osmotic-driven biofilm removal strategy that harnesses osmotic dynamics to remove entire biofilm structures physically. Internal osmotic pressure is generated by a precisely designed cationic copolymer, triggering controlled detachment of the biofilm matrix. When tested in vitro on Streptococcus mutans biofilms grown on dental aligners and in hard-to-reach interproximal spaces, our method eliminated biofilms more efficiently than traditional cleaning methods. The technique showed concentration-dependent cytotoxicity, highlighting the need for further polymer optimization. Overall, our osmotic-driven biofilm removal strategy significantly advances biofilm control strategies, offering a novel solution for improving oral health and presenting a potential physical removal method for medical settings.
生物膜引起的龋齿是现代牙科的一个重大挑战,特别是在校正器治疗中,生物膜在长期使用中很容易积聚并导致严重的风险。传统的抗菌方法侧重于杀死细菌,往往忽略了去除生物膜基质的重要任务,使细菌能够快速重新附着。在这项研究中,我们介绍了一种渗透驱动的生物膜去除策略,该策略利用渗透动力学来物理去除整个生物膜结构。内部渗透压由精确设计的阳离子共聚物产生,触发生物膜基质的受控脱离。当对生长在牙齿矫正器和难以触及的近端间隙中的变形链球菌生物膜进行体外测试时,我们的方法比传统的清洁方法更有效地消除了生物膜。该技术显示出浓度依赖性的细胞毒性,强调了进一步优化聚合物的必要性。总的来说,我们的渗透驱动生物膜去除策略显著推进了生物膜控制策略,为改善口腔健康提供了一种新的解决方案,并为医疗环境提供了一种潜在的物理去除方法。
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引用次数: 0
Activating Endogenous Condylar Stem Cells to Enhance TMJ Repair. 激活内源性髁突干细胞促进TMJ修复。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251363561
T Tuwatnawanit,N Anthwal,A S Tucker
The temporomandibular joint (TMJ) plays a critical role in the daily activities of mastication and communication, with disorders of the TMJ significantly impairing quality of life. Temporomandibular disorders (TMDs) are highly prevalent, presenting a pressing need for regenerative therapies. The TMJ's key components-condyle, TMJ disc, and glenoid fossa-are crucial for proper function; however, the limited self-repair capability of these tissues makes managing TMJ pathology particularly challenging. Emerging research in animal models has emphasized the importance of fibrocartilage stem/progenitor cells (FCSCs) located in and around the superficial layers of the condyle. Lineage tracing of condylar FCSCs in vivo has identified subpopulations with different contributions to growth and homeostasis, providing potential targets for regenerative therapies. In addition to the FCSCs, niche-supporting cells have been recently identified in the superficial layers of the condyle, further highlighting the complex cellular environment of the TMJ. Several signaling pathways, including Wnt, Hedgehog, and Notch, play pivotal roles in establishing cell fate in the developing and growing TMJ and have been additionally implicated in both the control of FCSC populations and progression of TMDs. Recent research has used this understanding of the signaling pathways involved in the creation of the joint to stimulate the endogenous stem cells/FCSCs of the adult in vivo, leading to enhancement of regenerative capacity in mouse, rat, rabbit, and porcine injury and disease models. Manipulation of signaling pathways has been combined with advanced bioengineering techniques, providing scaffolds to allow controlled dispersal of activators and inhibitors. Such advances in understanding the triggers and molecular mechanisms that control TMJ FCSCs, combined with improved targeting of specific signaling pathways, have opened new avenues for regenerative therapies. These insights have begun to be leveraged in the development of novel hydrogel-based injectable regenerative therapeutic approaches to not only alleviate symptoms but also promote true regeneration of TMJ structures.
颞下颌关节(TMJ)在咀嚼和交流的日常活动中起着至关重要的作用,颞下颌关节疾病严重影响生活质量。颞下颌紊乱(TMDs)非常普遍,迫切需要再生治疗。TMJ的关键组成部分——髁突、TMJ椎间盘和盂窝——对正常功能至关重要;然而,这些组织有限的自我修复能力使得管理TMJ病理特别具有挑战性。动物模型的新兴研究强调了位于髁状突浅层及其周围的纤维软骨干/祖细胞(FCSCs)的重要性。体内髁突FCSCs的谱系追踪已经确定了对生长和体内平衡有不同贡献的亚群,为再生治疗提供了潜在的靶点。除了FCSCs外,最近在髁状突的浅层中也发现了支持细胞,进一步强调了TMJ复杂的细胞环境。几种信号通路,包括Wnt、Hedgehog和Notch,在TMJ的发育和生长中起着关键作用,并且在FCSC群体的控制和TMDs的进展中也起着重要作用。最近的研究利用这种对参与关节形成的信号通路的理解来刺激体内成体的内源性干细胞/FCSCs,从而增强小鼠、大鼠、兔和猪损伤和疾病模型的再生能力。信号通路的操纵与先进的生物工程技术相结合,为激活剂和抑制剂的可控分散提供了支架。在了解控制TMJ FCSCs的触发因素和分子机制方面的这些进展,以及对特定信号通路的靶向性的改进,为再生治疗开辟了新的途径。这些见解已经开始被用于开发新的基于水凝胶的可注射再生治疗方法,不仅可以缓解症状,还可以促进TMJ结构的真正再生。
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引用次数: 0
A Biomimetic Li2Si2O5 Composite with High Energy Absorption for Endocrowns. 仿生高吸能Li2Si2O5复合材料的研究。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251368752
Z Ye,X Zhou,J Yu,X Chen,Y Huang,Q Xia,Y Xie,X Tong,Z Chen,Y Li,L Zhu,C Wen,J Lin,J Ma
Endocrowns represent a minimally invasive treatment option for endodontically treated teeth. However, in the anterior dentition, they are more likely to cause fractures in the abutment teeth due to the influence of lateral forces. Developing endocrowns that closely replicate the mechanical properties of the different components of natural teeth offers a promising strategy for improving the biomechanical performance of single-component restorations. Therefore, this study reports a novel multilevel ceramic composite achieved through fabrication of a diamond-topology lithium disilicate (LD) ceramic scaffold using vat photopolymerization, followed by toughening through potassium nitrate ion exchange (IE) and epoxy resin infiltration. This ceramic composite exhibited mechanical properties close to those of human dentin and therefore can prevent catastrophic stress-induced fractures of the abutment teeth due to enhanced toughness. Heating treatment and phase analyses were conducted to determine the optimal debinding and sintering parameters. Residual stress measurements, flexural strength testing, and microhardness evaluations were performed to assess the mechanical properties of the IE-toughened LD. In addition, the elastic modulus, compressive strength, and toughness of the ceramic composite were comprehensively characterized, using Vita Enamic and human dentin as reference materials. With the optimization of the heat-treatment and IE processes, the ceramic composite achieved a maximum compressive strength of 217 ± 11.8 MPa and a minimum elastic modulus of 3.7 ± 0.1 GPa, similar to the elastic modulus of human dentin (1.9 ± 0.4 GPa). In addition, the 0.25RD (relative density) composite group showed a maximum energy absorption of 37.7 ± 1.9 MJ/m³. The quasi in situ compression test revealed that the enhanced toughness primarily resulted from microcrack aggregation, interface delamination, and macroscopic crack splitting.
牙髓冠是牙髓治疗的一种微创治疗方法。然而,在前牙列,由于侧向力的影响,它们更容易导致基牙骨折。开发能够复制天然牙齿不同成分的力学特性的内冠,为提高单成分修复体的生物力学性能提供了一种很有前途的策略。因此,本研究报告了一种新的多层陶瓷复合材料,通过还原光聚合制备金刚石拓扑二硅酸锂(LD)陶瓷支架,然后通过硝酸钾离子交换(IE)和环氧树脂渗透增韧。该陶瓷复合材料具有接近人类牙本质的力学性能,因此由于增强的韧性可以防止基牙的灾难性应力引起的断裂。通过热处理和物相分析,确定了最佳的脱脂和烧结参数。通过残余应力测试、抗弯强度测试和显微硬度评估来评估ie增韧LD的力学性能,并以Vita Enamic和人牙本质为对照材料,对陶瓷复合材料的弹性模量、抗压强度和韧性进行综合表征。通过对热处理和IE工艺的优化,陶瓷复合材料的最大抗压强度为217±11.8 MPa,最小弹性模量为3.7±0.1 GPa,与人类牙本质的弹性模量(1.9±0.4 GPa)相近。相对密度为0.25RD的复合材料组吸能最大值为37.7±1.9 MJ/m³。准原位压缩试验表明,微裂纹聚集、界面分层和宏观裂纹劈裂是增强韧性的主要原因。
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引用次数: 0
Anxiety Promotes Occlusal Interference-Induced Myalgia via the Mesolimbic System. 焦虑通过中边缘系统促进咬合干扰诱导的肌痛。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-16 DOI: 10.1177/00220345251368273
Y J Zhang,Y Li,S Y Mo,J W Liu,X T Song,K Y Fu,Q F Xie,X X Xu,Y Cao
Acute occlusal interference may induce chronic masticatory myalgia in some individuals. The potential factors and underlying mechanisms that predispose one to occlusion-related masticatory myalgia remain unclear. Anxiety has been shown to facilitate pain perception. The ventral tegmental area, a critical component of the mesolimbic dopamine circuit, is involved in the neural networks shared by anxiety and pain. Whether anxiety levels influence masticatory myalgia induced by occlusal interference and what role the ventral tegmental area plays in this interaction have yet to be fully elucidated. In this study, we quantified the inborn variability in anxiety levels of male Sprague-Dawley rats using the elevated plus maze. We observed that high anxiety levels enhanced mechanical hypersensitivity in masseter muscle following application of experimental occlusion interference. Immunofluorescence and in vivo electrophysiologic experiments revealed differences in the activity of dopaminergic neurons and low-frequency oscillations in the ventral tegmental area of rats with varying anxiety levels following occlusion interference. Chemogenetic manipulations of dopaminergic neurons in the ventral tegmental area influenced the facilitatory effect of anxiety on occlusion interference-induced masseteric hyperalgesia. These findings provide the first evidence that anxiety can facilitate occlusion interference-induced masticatory myalgia, with the ventral tegmental area playing a crucial role in this neurobiological process.
急性咬合干扰可引起慢性咀嚼肌痛。潜在的因素和潜在的机制,使人倾向于咬合相关的咀嚼肌痛仍不清楚。焦虑已被证明能促进疼痛感知。腹侧被盖区是中边缘多巴胺回路的关键组成部分,它与焦虑和疼痛共享的神经网络有关。焦虑水平是否会影响咬合干扰引起的咀嚼肌痛,以及腹侧被盖区在这种相互作用中所起的作用尚未完全阐明。在这项研究中,我们量化了雄性Sprague-Dawley大鼠焦虑水平的先天变异性。我们观察到高焦虑水平会增强咬肌的机械超敏反应。免疫荧光和体内电生理实验揭示了不同焦虑水平的大鼠在闭塞干扰后腹侧被盖区多巴胺能神经元活性和低频振荡的差异。腹侧被盖区多巴胺能神经元的化学发生作用影响焦虑对咬合干扰诱发的咬痛过敏的促进作用。这些发现提供了第一个证据,表明焦虑可以促进咬合干扰引起的咀嚼肌痛,腹侧被盖区在这一神经生物学过程中起着至关重要的作用。
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引用次数: 0
Generative AI: Opportunities, Risks, and Responsibilities for Oral Sciences. 生成人工智能:口腔科学的机遇、风险和责任。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-15 DOI: 10.1177/00220345251356408
F Schwendicke,S K Sidhu,J L Ferracane,A Tichy,N S Jakubovics
Generative artificial intelligence (AI) has the capability to generate new content-including text, code, imagery, video, and speech-based on human prompts and is entering dental and oral research. By retrieving, analyzing, summarizing, and contextualizing vast datasets, generative AI offers substantial potential to enhance scientific workflows. It can improve documentation, communication, and reproducibility while saving time and accelerating discovery. However, its integration into research brings significant ethical, societal, and scientific challenges. Concerns include embedded data biases, automation bias, overreliance, and error propagation, all requiring critical human oversight. Furthermore, generative AI raises complex issues around plagiarism, fraud, attribution, and reproducibility, compounded by the potential for AI "hallucinations" or fabricated content. Addressing these concerns demands transparency, robust verification processes, ethical compliance, and clear documentation distinguishing synthetic from real-world data. Several scientific and regulatory bodies have published guidelines to support responsible AI use. Recommendations relevant to scientists in dental, oral, and craniofacial research include transparent disclosure of AI tools and methods, thorough verification of AI outputs, ethical oversight, and active monitoring. Scientists are urged to work collaboratively with stakeholders to enforce these principles and engage the public in the evolving discourse. The risk of misuse, particularly through fraudulent AI-generated publications, is growing. Paper mills exploiting generative AI can produce fabricated or manipulated articles, which may mislead the scientific community and distort evidence bases. Coordinated action, involving journals, institutions, and ethics bodies, is essential to combat these threats. As generative AI continues to evolve, adaptive and harmonized guidelines will be necessary to safeguard scientific integrity. Researchers, reviewers, and editors must play a proactive role in ensuring that AI serves to advance-not undermine-the quality and trustworthiness of dental and oral science.
生成式人工智能(AI)具有根据人类提示生成新内容的能力,包括文本、代码、图像、视频和语音,并且正在进入牙科和口腔研究领域。通过检索、分析、总结和背景化大量数据集,生成式人工智能为增强科学工作流程提供了巨大的潜力。它可以改进文档、通信和再现性,同时节省时间并加速发现。然而,将其整合到研究中带来了重大的伦理、社会和科学挑战。问题包括嵌入式数据偏差、自动化偏差、过度依赖和错误传播,所有这些都需要关键的人为监督。此外,生成式人工智能还引发了抄袭、欺诈、归因和可再现性等复杂问题,并可能产生人工智能“幻觉”或捏造内容。解决这些问题需要透明度、健壮的验证过程、道德遵从,以及区分合成数据和真实数据的清晰文档。一些科学和监管机构已经发布了支持负责任地使用人工智能的指导方针。与牙科、口腔和颅面研究科学家相关的建议包括透明地披露人工智能工具和方法,彻底核实人工智能产出,道德监督和积极监测。敦促科学家与利益相关者合作,执行这些原则,并让公众参与不断发展的话语。滥用的风险,特别是通过人工智能生成的欺诈性出版物,正在增加。造纸厂利用生成式人工智能可以生产捏造或操纵的文章,这可能会误导科学界并歪曲证据基础。涉及期刊、机构和伦理团体的协调行动对于对抗这些威胁至关重要。随着生成式人工智能的不断发展,有必要制定适应性和协调一致的指导方针,以维护科学的完整性。研究人员、审稿人和编辑必须发挥积极的作用,确保人工智能能够促进而不是破坏牙科和口腔科学的质量和可信度。
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引用次数: 0
Corrigendum to Molecular Profiling of Odontoclasts during Physiological Tooth Replacement 生理性牙齿置换过程中破牙细胞分子谱的勘误
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-03 DOI: 10.1177/00220345251384972
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引用次数: 0
The Remineralization Potential of Resveratrol and Cucurbit[n]uril. 白藜芦醇和瓜类的再矿化潜力[j]。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-03 DOI: 10.1177/00220345251350135
L Huang,X Yang,Z Bai,Y Lu,J Bian,H Xie,C Chen,K Chen
The degradation of exposed collagen fibers in the deep layers of dentin during bonding procedures hampers its durability. Inducing the remineralization of demineralized dentin areas and inhibiting collagen degradation can improve bonding durability. Resveratrol, a natural polyphenol, has garnered attention for its positive effects on bonding durability. The positive effects on dentin remineralization and matrix metalloproteinase (MMP) inhibition are concentration dependent; high concentrations increase cytotoxicity. This study investigated the use of complexes of resveratrol and cucurbit[n]uril (Q[6] and Q[7]) to maintain adequate concentrations and achieve a stable rate of release in the deep dentin layers without causing cytotoxicity. Resveratrol and Q[n] complexes (Res@Q[n]) were prepared and their structures and the extent of resveratrol release were examined using analytical chemistry methods and quantum chemical analysis. In addition, the effects of resveratrol and the complexes of Res@Q[n] on cell cytotoxicity, recombinant type I collagen and dentin mineralization, microtensile bond strength (µTBS), nanoleakage, rhMMP-9 colorimetric assays, and in situ zymography were compared. Resveratrol was stably released from the Res@Q[n] complexes for nearly a month, reducing the cell cytotoxicity of high concentrations of the polyphenol, exhibiting stronger inhibition of MMPs, and facilitating more pronounced remineralization of recombinant type I collagen and dentin. Pretreating the dentin surface with complexes significantly increased the µTBS values and reduced nanoleakage and MMP activity before and after aging compared with single resveratrol. In conclusion, Res@Q[n] complexes can promote the continuous stability of the hybrid layer and improve the durability of dentin bonding compared with resveratrol alone without inducing cytotoxicity.
在粘合过程中,暴露在牙本质深层的胶原纤维的降解会影响其耐久性。诱导牙本质脱矿区再矿化和抑制胶原降解可提高粘接耐久性。白藜芦醇是一种天然多酚,因其对粘合耐久性的积极影响而受到关注。对牙本质再矿化和基质金属蛋白酶(MMP)抑制的积极作用呈浓度依赖性;高浓度增加细胞毒性。本研究研究了白藜芦醇和瓜[n]脲(Q[6]和Q[7])的配合物在不引起细胞毒性的情况下,在牙本质深层维持足够的浓度并实现稳定的释放速率。制备了白藜芦醇和Q[n]配合物(Res@Q[n]),采用分析化学和量子化学方法对其结构和白藜芦醇释放度进行了表征。此外,我们还比较了白藜芦醇和Res@Q[n]复合物对细胞毒性、重组I型胶原和牙本质矿化、微拉伸键合强度(µTBS)、纳米渗漏、rhMMP-9比色和原位酶谱分析的影响。白藜芦醇从Res@Q[n]复合物中稳定释放近一个月,降低了高浓度多酚的细胞毒性,对MMPs表现出更强的抑制作用,促进重组I型胶原和牙本质更明显的再矿化。与单一白藜芦醇相比,用配合物预处理牙本质表面可显著提高老化前后的µTBS值,降低纳米渗漏和MMP活性。综上所述,与单独使用白藜芦醇相比,Res@Q[n]配合物可以促进杂化层的持续稳定性,提高牙本质结合的耐久性,而不会产生细胞毒性。
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引用次数: 0
Salivary Nitrate Maintains Mucosal Homeostasis via the Sialin-Neuropeptide Axis. 唾液硝酸盐通过唾液-神经肽轴维持粘膜稳态。
IF 7.6 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-09-22 DOI: 10.1177/00220345251362203
X Li,Z Cao,X Chen,Y Xu,H Liu,X Wang,J Wang,L Hu,S Wang
While saliva critically maintains oral homeostasis and accelerates mucosal repair, the molecular mediators driving this regenerative capacity remain unclear. Here, we identify salivary nitrate as a neuromodulatory signal coordinating oral mucosal regeneration through sensory neuron activation. In a palatal wound model, salivary nitrate depletion (via bilateral submandibular duct ligation or dietary restriction) impaired wound healing, characterized by reduced epithelial proliferation, aberrant collagen organization, and suppressed vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) expression-phenotypes rescued by nitrate supplementation. Transcriptomic profiling revealed that both nitrate-dependent upregulation of Rnf112 and the enhancement of the mucin type O-glycan biosynthesis pathway were mechanistically linked to myelinated sensory nerve modulation. Crucially, salivary nitrate promoted the reinnervation of myelinated sensory nerve fibers, upregulated the nitrate transporter sialin (Slc17a5), and stimulated the secretion of regenerative neuropeptides including calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y. In vitro, sialin knockdown abolished nitrate-induced cell proliferation and neuropeptide release in H4 cells while disrupting O-glycosylation, a key posttranslational modification for mucosal barrier function. Sensory neuron-specific sialin knockout mice (Slc17a5∆Trpv1, cKO) exhibited impaired neuropeptide release and failed to respond therapeutically to nitrate, confirming the indispensable role of sialin. These findings establish a sialin-dependent sensory neuropeptide axis wherein nitrate activates sensory neurons to drive mucosal regeneration, providing both mechanistic understanding of neuroepithelial crosstalk and a druggable target for tissue repair strategies.
虽然唾液维持口腔内稳态并加速粘膜修复,但驱动这种再生能力的分子介质尚不清楚。在这里,我们发现唾液硝酸盐是通过感觉神经元激活协调口腔粘膜再生的神经调节信号。在腭创面模型中,唾液硝酸盐消耗(通过双侧下颌下导管结扎或饮食限制)会损害创面愈合,其特征是上皮细胞增殖减少,胶原组织异常,血管内皮生长因子(VEGF)和转化生长因子-β (TGF-β)表达受到抑制。转录组学分析显示,硝酸盐依赖的Rnf112上调和粘蛋白型o -聚糖生物合成途径的增强与髓鞘感觉神经调节有机制联系。重要的是,唾液中的硝酸盐促进了有髓感觉神经纤维的再神经化,上调了硝酸盐转运蛋白sialin (Slc17a5),刺激了再生神经肽的分泌,包括降钙素基因相关肽、血管活性肠肽和神经肽y。在体外,sialin敲低可消除硝酸盐诱导的H4细胞增殖和神经肽释放,同时破坏了o糖基化。一个关键的翻译后修饰粘膜屏障功能。感觉神经元特异性sialin敲除小鼠(Slc17a5∆Trpv1, cKO)表现出神经肽释放受损,对硝酸盐没有治疗反应,证实了sialin不可或缺的作用。这些发现建立了唾液素依赖的感觉神经肽轴,其中硝酸盐激活感觉神经元以驱动粘膜再生,提供了神经上皮串音的机制理解和组织修复策略的可药物靶点。
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Journal of Dental Research
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