GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis.
GSK3 inhibitor-loaded osteotropic Pluronic hydrogel effectively mitigates periodontal tissue damage associated with experimental periodontitis.
复制标题
载GSK3通道的Pluronic水凝胶可有效减轻实验性牙周炎相关的牙周组织损伤。
DOI：
10.1016/j.biomaterials.2020.120293
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发表时间：
2020-12
期刊：
影响因子：
14
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Almoshari Y;Ren R;Zhang H;Jia Z;Wei X;Chen N;Li G;Ryu S;Lele SM;Reinhardt RA;Wang D
牙周炎是一种慢性炎症性疾病，由宿主免疫系统和影响牙周组织完整性的病原体之间的复杂相互作用引起。为了防止疾病进展，从而保护牙槽骨结构，同时抗炎和成骨干预是必不可少的。因此，选择糖原合成酶激酶3 β抑制剂（BIO）作为有效的炎症调节剂和成骨剂，以实现该治疗目标。然而，BIO缺乏向骨性、水溶性差以及潜在的长期全身副作用阻碍了其临床应用。为了解决这些局限性，合成了焦磷酸化Pluronic F127（F127-PPi），并与常规F127混合以制备BIO的可注射和温敏水凝胶制剂（PF 127），其可以粘附于硬组织并逐渐释放BIO以局部发挥其治疗作用。与F127水凝胶相比，PF 127水凝胶表现出更强的与羟基磷灰石（HA）的结合。此外，BIO在PF 127溶液中的溶解度相对于F127溶液显著提高，并且该提高与聚合物浓度成比例。当在牙周炎大鼠模型上进行评估时，发现PF 127-BIO水凝胶治疗在保护牙槽骨和韧带以及预防牙周炎症方面非常有效，分别如micro-CT和组织学数据所示。总之，这些发现表明，热响应性PF 127水凝胶是一种有效的局部药物递送系统，用于更好地临床管理牙周炎和相关病理。
Periodontitis is a chronic inflammatory disease caused by complex interactions between the host immune system and pathogens that affect the integrity of periodontium. To prevent disease progression and thus preserve alveolar bone structure, simultaneous anti-inflammatory and osteogenic intervention are essential. Hence, a glycogen synthase kinase 3 beta inhibitor (BIO) was selected as a potent inflammation modulator and osteogenic agent to achieve this treatment objective. BIO’s lack of osteotropicity, poor water solubility, and potential long-term systemic side effects, however, have hampered its clinical applications. To address these limitations, pyrophosphorylated Pluronic F127 (F127-PPi) was synthesized and mixed with regular F127 to prepare an injectable and thermoresponsive hydrogel formulation (PF127) of BIO, which could adhere to hard tissue and gradually release BIO to exert its therapeutic effects locally. Comparing to F127 hydrogel, PF127 hydrogels exhibited stronger binding to hydroxyapatite (HA). Additionally, BIO’s solubility in PF127 solution was dramatically improved over F127 solution and the improvement was proportional to the polymer concentration. When evaluated on a rat model of periodontitis, PF127-BIO hydrogel treatment was found to be very effective in preserving alveolar bone and ligament, and preventing periodontal inflammation, as shown by the micro-CT and histological data, respectively. Altogether, these findings suggested that the thermoresponsive PF127 hydrogel is an effective local drug delivery system for better clinical management of periodontitis and associated pathologies.
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DOI：
10.1016/j.jdsr.2017.11.003
发表时间：
2018-05
期刊：
The Japanese dental science review
影响因子：
--
作者：
Fujita T;Yoshimoto T;Kajiya M;Ouhara K;Matsuda S;Takemura T;Akutagawa K;Takeda K;Mizuno N;Kurihara H
通讯作者：
Kurihara H
影响因子：
17.1
作者：
Jia Z;Wang X;Wei X;Zhao G;Foster KW;Qiu F;Gao Y;Yuan F;Yu F;Thiele GM;Bronich TK;O'Dell JR;Wang D
通讯作者：
Wang D
影响因子：
6.7
作者：
Herrera, D;Sanz, M;Roldán, S
通讯作者：
Roldán, S
影响因子：
2.9
作者：
Fukuda, Toru;Kokabu, Shoichiro;Katagiri, Takenobu
通讯作者：
Katagiri, Takenobu
影响因子：
4.1
作者：
Georgiou, Kristen R.;King, Tristan J.;Xian, Cory J.
通讯作者：
Xian, Cory J.