Luo Aoxiang, Yao Yao, Chen Yuejing, Li Zongbo, Wang Xiaoyan
Department of cariology and Endodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices& Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, PR China; Stomatological Center, Peking University Shenzhen Hospital, Guangdong Provincial High-level Clinical Key Specialty, Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment, The Institute of Stomatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong 518036, PR China.
Stomatological Center, Peking University Shenzhen Hospital, Guangdong Provincial High-level Clinical Key Specialty, Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment, The Institute of Stomatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong 518036, PR China.
Int J Biol Macromol. 2025 Apr;303:140434. doi: 10.1016/j.ijbiomac.2025.140434. Epub 2025 Jan 28.
Periodontitis is a chronic inflammatory condition mainly caused by the interaction between the host immune system and periodontal tissue pathogens, and may lead to consequences, such as alveolar bone defects and tooth loss. Incomplete bacterial removal, persistent inflammation and high reactive oxygen species (ROS) environment are the main challenges for periodontal tissue repair and alveolar bone regeneration. In this study, an injectable composite microgel (Gelatin methacryloyl-Phenylboronic acid/Hydroxyadamantane, GPH) loaded with antimicrobial peptide (AMP) and cerium dioxide (CeO) microspheres was developed to achieve a synergistic function of bacteriostasis, immunomodulation, and ROS removal. In vitro studies had shown that the composite microgel had an inhibitory rate of >99 % against E. coli, S. aureus and P. gingivalis and scavenged DPPH with a rate of 87.1 % ± 2.0 %, exhibiting excellent antibacterial and antioxidant properties. In addition, it was able to promote macrophage phenotypic shift from M1-type to M2-type and reduce ROS levels, and also had excellent biocompatibility. Mechanistically, the composite microgel was subjected to transcriptome sequencing analysis of gene expression levels and signaling pathways in BMSC cells, and the results showed that the microgel played an important role in regulating the PI3K-Akt and chemokine signaling pathways, which in turn inhibited the expression of inflammatory factors. In vivo the effect of composite microgel on periodontal tissue repair and alveolar bone regeneration was verified by infected alveolar bone defect model. The results showed that after 4 weeks of using the composite microgel, the bone volume per unit of tissue volume of the alveolar bone, the thickness of bone trabeculae, and the bone mineral density reached 25.94 % ± 0.03 %, 0.14 mm ± 0.01 mm, and 0.442 g/cm ± 0.003 g/cm, respectively, while those of the control group were 22.3 % ± 0.29 %, 0.07 mm ± 0.02 mm, and 0.236 g/cm ± 0.059 g/cm, respectively, and the use of the composite microgel resulted in significantly better repair results than the control group. In addition, pro-inflammatory factors were significantly suppressed and inflammation levels were significantly reduced. Overall, this composite microgel showed great potential in reducing inflammation levels and promoting alveolar bone regeneration, providing an innovative approach to the treatment of periodontitis.
牙周炎是一种慢性炎症性疾病，主要由宿主免疫系统与牙周组织病原体之间的相互作用引起，可能导致牙槽骨缺损和牙齿脱落等后果。细菌清除不完全、持续性炎症和高活性氧（ROS）环境是牙周组织修复和牙槽骨再生的主要挑战。在本研究中，开发了一种负载抗菌肽（AMP）和二氧化铈（CeO）微球的可注射复合微凝胶（甲基丙烯酰化明胶-苯硼酸/羟基金刚烷，GPH），以实现抑菌、免疫调节和ROS清除的协同功能。体外研究表明，该复合微凝胶对大肠杆菌、金黄色葡萄球菌和牙龈卟啉单胞菌的抑制率>99%，对DPPH的清除率为87.1%±2.0%，具有优异的抗菌和抗氧化性能。此外，它能够促进巨噬细胞表型从M1型向M2型转变并降低ROS水平，还具有优异的生物相容性。机制上，对复合微凝胶进行了骨髓间充质干细胞（BMSC）细胞基因表达水平和信号通路的转录组测序分析，结果表明该微凝胶在调节PI3K-Akt和趋化因子信号通路中起重要作用，进而抑制炎症因子的表达。在体内，通过感染性牙槽骨缺损模型验证了复合微凝胶对牙周组织修复和牙槽骨再生的作用。结果显示，使用复合微凝胶4周后，牙槽骨单位组织体积的骨体积、骨小梁厚度和骨密度分别达到25.94%±0.03%、0.14mm±0.01mm和0.442g/cm±0.003g/cm，而对照组分别为22.3%±0.29%、0.07mm±0.02mm和0.236g/cm±0.059g/cm，使用复合微凝胶的修复效果明显优于对照组。此外，促炎因子受到显著抑制，炎症水平显著降低。总体而言，这种复合微凝胶在降低炎症水平和促进牙槽骨再生方面显示出巨大潜力，为牙周炎的治疗提供了一种创新方法。
