Hyaluronic acid-g-lipoic acid granular gel for promoting diabetic wound healing.
Hyaluronic acid-g-lipoic acid granular gel for promoting diabetic wound healing.
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DOI：
10.1002/btm2.10402
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发表时间：
2023-03
影响因子：
7.4
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中科院分区：
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糖尿病患者在创伤后容易发生慢性炎症，并且具有持续的不愈合伤口。长期伤口部位的活性氧（ROS）和复发性细菌感染也会进一步延迟皮肤伤口愈合和组织再生。在这项研究中，基于透明质酸-g-硫辛酸（HA-LA）制备颗粒凝胶（具有ROS清除和抗菌特性）。简言之，合成HA-LA以制备HA-LA微凝胶，其通过Ag+与二硫戊环中的二硫化物的配位作用进一步组装以形成颗粒凝胶。可挤出的散装颗粒凝胶具有剪切稀化特征，并且在挤出后立即恢复为固态，并且这可以容易地应用于整个伤口区域。因此，接枝的LA不仅可以构建颗粒凝胶，还可以从微环境中去除过量的活性氧。此外，Ag+的存在实现了微凝胶的组装，并具有抗菌作用。体内实验表明，HA‐LA颗粒凝胶可消除伤口部位过量的ROS，并上调修复生长因子的分泌，从而显著加速普通和糖尿病伤口愈合。因此，可应用于慢性炎症创面的ROS清除颗粒凝胶显示出强大的临床实用性。
Diabetic patients are prone to developing chronic inflammation after trauma and have persistent nonhealing wounds. Reactive oxygen species (ROS) and recurrent bacterial infections at the site of long‐term wounds also further delay skin wound healing and tissue regeneration. In this study, a granular gel (which exhibits ROS scavenging and antibacterial properties) is fabricated based on hyaluronic acid‐g‐lipoic acid (HA‐LA). Briefly, HA‐LA is synthesized to fabricate HA‐LA microgels, which are further assembled by Ag+ via its coordination effect with disulfide in dithiolane to form a granular gel. The extrudable bulk granular gel possesses a shear‐thinning feature and is immediately restored to a solid state after extrusion, and this can be easily applied to the whole wound area. Therefore, the grafted LA not only allows for the construction of the granular gel but also removes excess ROS from the microenvironment. Additionally, the presence of Ag+ realizes the assembly of microgels and has antibacterial effects. In vivo experiments show that the HA‐LA granular gel eliminates excessive ROS at the wound site and up‐regulates the secretion of reparative growth factors, thus, accelerating common and diabetic wound healing significantly. Therefore, the ROS‐scavenging granular gel that can be applied to the wound surface with chronic inflammation demonstrates strong clinical utility.