Multifunctional Injectable Bioadhesive with Toll-like Receptor 4 and Myeloid Differentiation Factor 2 Antagonistic Anti-inflammatory Potential for Periodontal Regeneration

作者：Shuting Gao, Huihua Li, Zekun Li, Hong Wang, Xinyue Li, Shengyan Yang, Lin Huang, Baoping Zhang, Kailiang Zhang, James Kit Hon Tsoi, Jian He, Waruna Lakmal Dissanayaka · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c15922 · 被引用次数：12 · 研究领域：Oral microbiology and periodontitis research、Periodontal Regeneration and Treatments、Bone and Dental Protein Studies

High Resolution Image Download MS PowerPoint Slide Effectively addressing inflammation in periodontitis is challenging as conventional injectable hydrogels typically require the addition of drugs to provide sufficient anti-inflammatory effects. To overcome this limitation, we developed a multifunctional injectable hydrogel with inherent properties that antagonize the Toll-like receptor 4 and myeloid differentiation factor 2 complex (TLR4-MD2). This hydrogel allows for direct inhibition of inflammatory pathways without the need for additional drugs. We identified xylitol, caffeic acid, and citric acid as natural materials that effectively meet biological needs for anti-inflammatory and antibacterial effects as well as support bone regeneration. With this in mind, we developed a caffeic-acid-modified poly(xylitol succinate) (PXS)-based iCPC@MgO composite hydrogel and tested its potential application for periodontal regeneration. The iCPC@MgO hydrogel demonstrated rapid wet tissue adhesion and injectability, which are ascribed to incorporating catechol groups derived from caffeic acid. Intriguingly, the PXS polymer used for synthesizing the hydrogel was found to possess anti-inflammatory properties and act as an antagonist for the TLR4-MD2 complex. This hydrogel also exhibited outstanding antibacterial efficiency against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans by stimulating antibiotic synthesis within bacteria and disrupting bacterial cell walls. In a...