Zhang Wenbiao, Wu Weiwei, Wang Tao, Wu Zhiwei, Li Yang, Ding Tao, Fang Zhennan, Tian Dasheng, He Xiaoyan, Huang Fei
Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.
Department of Anaesthesia, The First Affiliated Hospital of Anhui Medical University North district, Anhui Public Health Clinical Center, Hefei, Anhui, 230011, China.
Adv Healthc Mater. 2024 Dec;13(31):e2402092. doi: 10.1002/adhm.202402092. Epub 2024 Sep 3.
Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4) hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.
多功能响应性水凝胶在糖尿病足溃疡（DFU）治疗方面具有巨大潜力，尽管其复杂的设计和制造带来了挑战。本研究介绍了一种采用动态共价策略开发的新型超分子鸟苷 - 苯基硼酸 - 绿原酸（GBC）水凝胶。该水凝胶通过在钾离子存在下鸟苷四链体组装以及经由动态硼酸酯键的绿原酸（CA）连接而形成。GBC水凝胶表现出pH和葡萄糖响应性，由于硼酸酯键解离和G - 四链体（G4）水凝胶解体，在酸性和高葡萄糖条件下释放更多绿原酸。实验结果表明，GBC水凝胶具有良好的自愈性、剪切变稀性、可注射性和溶胀性能。体外和体内研究均表明，GBC水凝胶具有良好的生物相容性，能够消除细菌和活性氧（ROS），促进巨噬细胞从M1表型向M2表型极化（降低CD86表达并增加CD206表达），表现出抗炎作用（降低TNF - α表达并增加IL - 10表达），并促进血管生成（增加VEGF、CD31和α - SMA表达）。因此，GBC水凝胶加速DFU愈合并增强组织重塑和胶原蛋白沉积。这项工作为开发响应性水凝胶以加速DFU愈合提供了一种新方法。
