National Engineering Research Center for Nanomedicine and Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Bioinformatics and Molecular Imaging, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Nat Commun. 2024 Nov 12;15(1):9786. doi: 10.1038/s41467-024-54075-7.
Diabetic wounds are usually entangled in a disorganized and self-perpetuating microenvironment and accompanied by a prolonged delay in tissue repair. Sustained and coordinated microenvironment regulation and tissue regeneration are key to the healing process of diabetic wounds, yet they continue to pose a formidable challenge. Here we report a rational double-layered dressing design based on chitosan and a degradable conjugated polymer polydiacetylene, poly(deca-4,6-diynedioic acid) (PDDA), that can meet this intricate requirement. With an alternating ene-yne backbone, PDDA degrades when reacting with various types of reactive oxygen species (ROS), and more importantly, generates proliferative succinic acid as a major degradant. Inheriting from PDDA, the developed PDDA-chitosan double layer dressing (PCD) can eliminate ROS in the microenvironment of diabetic wounds, alleviate inflammation, and downregulate gene expression of innate immune receptors. PCD degradation also triggers simultaneous release of succinic acid in a sustainable manner, enabling long-term promotion on tissue regeneration. We have validated the biocompatibility and excellent performance of PCD in expediting the wound healing on both diabetic mouse and porcine models, which underscores the significant translational potential of this microenvironment-modulating, growth-promoting wound dressing in diabetic wounds care.
糖尿病伤口通常陷入紊乱且自我维持的微环境中，并伴有组织修复的长时间延迟。持续协调的微环境调节和组织再生是糖尿病伤口愈合过程的关键，但它们仍然是一个巨大的挑战。在这里，我们报告了一种基于壳聚糖和可降解共轭聚合物聚二乙炔（polydiacetylene，PDDA）的合理双层敷料设计，它可以满足这一复杂的要求。具有交替的烯炔骨架，PDDA 与各种类型的活性氧（reactive oxygen species，ROS）反应时会降解，更重要的是，会产生增殖性琥珀酸作为主要降解产物。从 PDDA 继承而来，开发的 PDDA-壳聚糖双层敷料（PDDA-chitosan double layer dressing，PCD）可以消除糖尿病伤口微环境中的 ROS，减轻炎症，并下调固有免疫受体的基因表达。PCD 的降解还会以可持续的方式触发琥珀酸的同时释放，从而长期促进组织再生。我们已经验证了 PCD 在加速糖尿病小鼠和猪模型的伤口愈合方面的生物相容性和优异性能，这突显了这种调节微环境、促进生长的伤口敷料在糖尿病伤口护理方面的重要转化潜力。
