Alleviate Periodontitis and Its Comorbidity Hypertension using a Nanoparticle-Embedded Functional Hydrogel System,Advanced Healthcare Materials

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Alleviate Periodontitis and Its Comorbidity Hypertension using a Nanoparticle-Embedded Functional Hydrogel System
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-03-27 , DOI: 10.1002/adhm.202203337
Shuo Xu _{1,

2} , Bin Hu _{3,

4} , Ting Dong _{2,

5} , Bo-Yan Chen ₂ , Xiao-Jian Xiong _{3,

4} , Lin-Juan Du ₂ , Yu-Lin Li ₂ , Yan-Lin Chen ₆ , Guo-Cai Tian ₂ , Xue-Bing Bai _{2,

7} , Ting Liu ₂ , Lu-Jun Zhou ₂ , Wu-Chang Zhang ₂ , Yan Liu ₂ , Qin-Feng Ding ₂ , Xue-Qing Zhang _{3,

4} , Sheng-Zhong Duan _{1,

2}

Affiliation

Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200062, China.
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200062, China.
Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, 200240, China.
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200062, China.
Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200062, China.

Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled-release composite hydrogel approach is proposed with dual antibacterial and anti-inflammatory activities as a resolution to achieve the goal of co-treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross-linked with antimicrobial peptide (AMP)-modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS-PA). Subsequently, curcumin loaded into biodegradable nanoparticles (CNP) are embedded in the hydrogel exhibiting high encapsulation efficiency and sustained release to achieve long-term anti-inflammatory activities. In a mouse model of periodontitis complicated with hypertension, CS-PA/CNP is applied to gingival sulcus and produced an optimal therapeutic effect on periodontitis and hypertension simultaneously. The therapeutic mechanisms are deeply studied and indicated that CS-PA/CNP exerted excellent immunoregulatory effects by suppressing the accumulation of lymphocytes and myeloid cells and enhanced the antioxidant capacity and thus the anti-inflammatory capacity of macrophages through the glutathione metabolism pathway. In conclusion, CS-PA/CNP has demonstrated its superior therapeutic effects and potential clinical translational value in the co-treatment of periodontitis and hypertension, and also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.

中文翻译：

使用纳米颗粒嵌入的功能性水凝胶系统缓解牙周炎及其合并症高血压

牙周炎和高血压常常作为合并症出现，需要同时治疗。为了解决这个问题，提出了一种具有双重抗菌和抗炎活性的控释复合水凝胶方法，以实现共治并发症的目标。具体来说，具有固有抗菌特性的壳聚糖（CS）与抗菌肽（AMP）修饰的聚乙二醇（PEG）交联形成双重抗菌水凝胶（CS-PA）。随后，将姜黄素负载到可生物降解纳米粒子（CNP）中，嵌入水凝胶中，表现出高封装效率和持续释放，以实现长期抗炎活性。在牙周炎并发高血压小鼠模型中，将CS-PA/CNP应用于龈沟，同时对牙周炎和高血压产生最佳治疗效果。深入的治疗机制研究表明，CS-PA/CNP通过抑制淋巴细胞和骨髓细胞的积累发挥优异的免疫调节作用，并通过谷胱甘肽代谢途径增强巨噬细胞的抗氧化能力，从而增强巨噬细胞的抗炎能力。综上所述，CS-PA/CNP在牙周炎和高血压联合治疗中表现出优越的治疗效果和潜在的临床转化价值，也可以作为药物递送平台，为发病机制复杂的牙周炎提供组合治疗选择。

更新日期：2023-03-27

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