Li Yang, Fu Rongzhan, Duan Zhiguang, Zhu Chenhui, Fan Daidi
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an 710069, Shaanxi, China.
Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, Shaanxi, China.
ACS Nano. 2022 May 24;16(5):7486-7502. doi: 10.1021/acsnano.1c10575. Epub 2022 May 9.
Hypoxia, excessive reactive oxygen species (ROS), impaired angiogenesis, lasting inflammation, and bacterial infection, are key problems impeding diabetic wound healing. Particularly, controllable oxygen release and ROS scavenging capacities are critical during the wound healing process. Here, an injectable hydrogel based on hyaluronic acid--dopamine (HA-DA) and polydopamine (PDA) coated TiC MXene nanosheets is developed catalytically cross-linked by an oxyhemoglobin/hydrogen (HbO/HO) system combined with mild photothermal stimulation for diabetic wound healing. HbO not only acts as a horseradish peroxidase-like to catalyze the hydrogel formation but also as an oxygen carrier to controllably release oxygen when activated by the mild heat produced from near-infrared (NIR) irradiation. Specifically, HbO can provide oxygen repeatedly by binding oxygen in the air when the NIR is off. The stable photoresponsive heating behavior of MXene ensures the repeatable oxygen release. Additionally, artificial nonenzymatic antioxidant MXene nanosheets are proposed to scavenge excessive reactive nitrogen species and ROS including HO, O, and OH, keeping the intracellular redox homeostasis and alleviating oxidative stress, and eradicate bacteria to avoid infection. The antioxidant and antibacterial abilities of MXene are further improved by PDA coating, which also promotes the MXene nanosheets cross-linking into the network of the hydrogel. HA-DA molecules endow the hydrogel with the capacity to regulate macrophage polarization from M1 to M2 to achieve anti-inflammation. More importantly, the MXene-anchored hydrogel with multifunctions including tissue adhesion, self-healing, injectability, and hemostasis, combined with mild photothermal stimulation, greatly promotes human umbilical vein endothelial cell proliferation and migration and notably facilitates infected diabetic wound healing.
缺氧、过量的活性氧（ROS）、血管生成受损、持续炎症和细菌感染是阻碍糖尿病伤口愈合的关键问题。特别是，可控的氧气释放和ROS清除能力在伤口愈合过程中至关重要。在此，基于透明质酸-多巴胺（HA-DA）和聚多巴胺（PDA）包覆的TiC MXene纳米片开发了一种可注射水凝胶，通过氧合血红蛋白/氢气（HbO/H₂）系统结合温和的光热刺激进行催化交联，用于糖尿病伤口愈合。HbO不仅作为类似辣根过氧化物酶的物质催化水凝胶形成，还作为氧载体，在近红外（NIR）照射产生的温和热量激活时可控地释放氧气。具体而言，当NIR关闭时，HbO可以通过结合空气中的氧气反复提供氧气。MXene稳定的光响应加热行为确保了氧气的可重复释放。此外，提出了人工非酶抗氧化剂MXene纳米片来清除过量的活性氮物种和ROS，包括H₂O₂、O₂⁻和·OH，维持细胞内氧化还原稳态并减轻氧化应激，以及根除细菌以避免感染。PDA涂层进一步提高了MXene的抗氧化和抗菌能力，这也促进了MXene纳米片交联到水凝胶网络中。HA-DA分子赋予水凝胶调节巨噬细胞从M1向M2极化以实现抗炎的能力。更重要的是，具有组织粘附、自愈合、可注射性和止血等多种功能的MXene锚定水凝胶，结合温和的光热刺激，极大地促进了人脐静脉内皮细胞的增殖和迁移，并显著促进了感染性糖尿病伤口的愈合。
