慢性糖尿病伤口的处理是一个复杂的问题,需要伤口修复,调节炎症水平,以及预防细菌感染的干预措施。为了解决这个问题,我们开发了一种多功能光热响应水凝胶(PAG-CuS)作为管理整个伤口愈合过程的有效平台,包括促进伤口愈合,提供抗炎治疗,并进行光热灭菌。通过丙烯酸(AA)的共聚构建,甲基丙烯酸酐改性明胶(GelMA),和硫辛酸钠(LAS)包覆的硫化铜纳米颗粒(CuS@LAS),PAG-CuS具有促进细胞粘附的多孔三维结构,并具有相当大的保水能力。此外,内部CuS@LAS不仅赋予水凝胶光热抗菌性能,而且还用作物理交联剂,从而提高其机械强度。在近红外诱导的光热效应下,多孔水凝胶释放出CuS@LAS,后来CuS@LAS通过胶束解组装排出LAS以消除细胞内ROS。这导致MMP-9表达下调,促进ECM产生并促进伤口愈合。同时,PAG-CuS释放Cu2+可以增强内皮细胞CD31的表达,促进微血管形成,这对伤口愈合至关重要。在GK大鼠糖尿病创面模型中,PAG-CuS水凝胶降低了ROS水平,增加微血管计数,改善上皮形成,和增强伤口愈合。因此,这种多功能的光热水凝胶具有应用于灭菌的潜力,清除自由基,促进血管生成,使其成为管理糖尿病伤口挑战的有效和全面的解决方案。重要性声明:评估功能恢复和及时调整治疗策略在慢性糖尿病伤口的管理中至关重要。在这项工作中,我们通过集成原位还原制备了PAG-CuS复合水凝胶,化学交联,和纳米增强技术。PAG-CuS凝胶的近红外光诱导的光热效应迅速杀死病变部位的细菌,产生的热量同时促进了LAS从凝胶中的多级释放,通过调节ROS和MMP-9的水平促进细胞外基质的形成。此外,从凝胶中释放的Cu2+可以促进血管的形成以改善血液氧合。因此,本项目提出了实现全程管理加速糖尿病慢性创面愈合的协同方案。
The management of chronic diabetic wounds is a complex issue that requires wound repair, regulation of inflammatory levels, and intervention to prevent bacterial infection. To address this issue, we developed a multifunctional photothermally responsive hydrogel (PAG-CuS) as an effective platform for managing the entire wound-healing process, including promoting wound healing, providing anti-inflammatory therapy, and performing photothermal sterilization. Constructed through copolymerization of acrylic acid (AA), methacrylic anhydride-modified gelatin (GelMA), and lipoic acid sodium (LAS) coated copper sulfide nanoparticles (CuS@LAS), PAG-CuS possessed a porous three-dimensional structure that promoted cell adhesion and had a substantial water-holding capacity. Additionally, the internal CuS@LAS not only conferred photothermal antibacterial properties to the hydrogel but also served as physical cross-linking agents, thus enhancing its mechanical strength. Under the NIR-induced photothermal effect, the porous hydrogel liberates CuS@LAS, and later CuS@LAS expels LAS via micelle deassembly to eliminate intracellular ROS. This results in the down-regulation of MMP-9 expression, promoting ECM production and facilitating wound healing. Meanwhile, the release of Cu2+ from PAG-CuS could enhance CD31 expression in endothelial cells, promoting microvessel formation, which is crucial for wound healing. In the diabetic wound model of GK rats, the PAG-CuS hydrogel reduced ROS levels, increased microvessel count, improved epithelialization, and enhanced wound healing. Therefore, this versatile photothermal hydrogel has the potential to be applied in sterilization, scavenging free radicals, and promoting angiogenesis, making it an effective and comprehensive solution to manage the challenges of diabetic wounds. STATEMENT OF SIGNIFICANCE: Assessment of functional recovery and timely adjustment of treatment strategy is critical in the management of chronic diabetic wounds. In this work, we prepared PAG-CuS composite hydrogels by integrating in situ reduction, chemical crosslinking, and nanoenhancement techniques. The near-infrared light-induced photothermal effect of PAG-CuS gel rapidly kills bacteria at the lesion site, and the generated heat simultaneously promotes the multilevel release of LAS from the gel, which could regulate the levels of ROS and MMP-9 to promote extracellular matrix formation. In addition, the Cu2+ released from the gel can promote the formation of blood vessels to improve blood oxygenation. Therefore, this project proposes a synergistic solution to realize the whole process of management to accelerate chronic diabetic wound healing.