Qian Junmin, Ji Lijie, Xu Weijun, Hou Guanghui, Wang Jinlei, Wang Yaping, Wang Taibing
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
ACS Appl Mater Interfaces. 2022 Apr 13;14(14):16018-16031. doi: 10.1021/acsami.2c01254. Epub 2022 Mar 30.
Bacterial infection and delayed healing are two major obstacles in cutaneous wound management, and developing multifunctional hydrogels with antibacterial and prohealing capabilities presents a promising strategy to dress wounds. However, the simple and facile fabrication of such hydrogel dressings remains challenging. Herein, we report the first observation on hydrazide-metal coordination crosslinking that is utilized to successfully construct a series of hyaluronan (HA)-metal hydrogels by mixing hydrazided HA and metal ion solutions. Considering the antibacterial, prohealing, and proangiogenic properties of HA and Cu(II), as a proof of principle, a HA-Cu hydrogel was systematically investigated as a wound dressing. Surprisingly, the hydrazide-Cu(II) coordination was dynamic in nature and imparted the HA-Cu hydrogel with physicochemical multifunctions, including spontaneous self-healing, shear-thinning injectability, reversible pH/redox/ion pair triple responsiveness, etc. Moreover, the HA-Cu hydrogel exhibited a robust broad-spectrum antibacterial activity and could significantly accelerate infectious wound healing. Impressively, glutathione-triggered hydroxyl radical generation further potentiated wound healing, providing a paradigm for on-demand antibacterial activity enhancement. Hence, the HA-Cu hydrogel is a clinically applicable "smart" dressing for multi-scenario wound healing. We envision that the simple and versatile coordination approach opens up a new avenue to develop multifunctional hydrogels and shows great potential in frontier fields, such as biomedicine, wearable devices, and soft robots.
细菌感染和愈合延迟是皮肤伤口处理中的两大主要障碍，开发具有抗菌和促进愈合能力的多功能水凝胶是一种很有前景的伤口敷料策略。然而，这种水凝胶敷料的简单便捷制备仍然具有挑战性。在此，我们首次报道了利用酰肼-金属配位交联，通过将酰肼化透明质酸（HA）与金属离子溶液混合，成功构建了一系列HA-金属水凝胶。考虑到HA和铜（II）的抗菌、促进愈合和促血管生成特性，作为原理验证，对HA-Cu水凝胶作为伤口敷料进行了系统研究。令人惊讶的是，酰肼-铜（II）配位本质上是动态的，赋予了HA-Cu水凝胶多种物理化学功能，包括自发自愈、剪切变稀可注射性、可逆的pH/氧化还原/离子对三重响应性等。此外，HA-Cu水凝胶表现出强大的广谱抗菌活性，能够显著加速感染伤口的愈合。令人印象深刻的是，谷胱甘肽引发的羟基自由基生成进一步促进了伤口愈合，为按需增强抗菌活性提供了一个范例。因此，HA-Cu水凝胶是一种适用于多种场景伤口愈合的临床应用“智能”敷料。我们设想，这种简单通用的配位方法为开发多功能水凝胶开辟了一条新途径，并在生物医学、可穿戴设备和软机器人等前沿领域显示出巨大潜力。
