College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, P. R. China.
Experimental and Research Animal Institute, Sichuan University, Chengdu 610065, P. R. China.
ACS Appl Mater Interfaces. 2024 Nov 6;16(44):59862-59879. doi: 10.1021/acsami.4c13220. Epub 2024 Oct 23.
Chronic refractory wounds have become a serious threat to human health and are characterized by prolonged inflammation, recurrent bacterial infections, and elevated ROS levels. However, current therapeutic strategies usually target a unilateral healing function and are unable to tackle the complexity and sensitivity of chronic refractory wound healing. This study fabricated a biomimetic nanozyme based on rhein (Cu-rhein NSs), which effectively mimics the activity of superoxide dismutase (SOD) for scavenging various free radicals. Additionally, zinc oxide microspheres (ZnO MSs) were prepared to enhance the antibacterial activity and mechanical properties of the modified hydrogel. Cu-rhein NSs and ZnO MSs were comodified onto an extracellular matrix-mimetic dual-network smart hydrogel constructed from oxidized sodium alginate, gelatin, and borax via dynamic borate and Schiff base bonds. The smart hydrogel presented the good biocompatibility and targeted the unique acidic microenvironment with high oxidative stress of chronic refractory wounds, intelligently releasing bionic nanozymes to effectively eliminate bacteria, reduce inflammatory responses, and scavenge multiple free radicals for reducing ROS. In vivo experiments on the rat model based on diabetic infection showed that the smart hydrogel could effectively eliminate bacteria, promote vascular regeneration and collagen deposition, reduce inflammatory response, and accelerate the healing of diabetic-infected wounds (almost complete healing within 14 days). The advantages of an intelligent, biomimetic tissue regeneration cascade management strategy against diabetic infected wound healing are highlighted.
慢性难治性创面已成为严重威胁人类健康的难题，其具有炎症迁延不愈、反复发作细菌感染和活性氧（ROS）水平升高等特点。然而，目前的治疗策略通常针对单一的愈合功能，无法应对慢性难治性创面愈合的复杂性和敏感性。本研究制备了一种基于大黄素（Cu-rhein NSs）的仿生纳米酶，其可有效模拟超氧化物歧化酶（SOD）的活性，用于清除各种自由基。此外，还制备了氧化锌微球（ZnO MSs）以增强改性水凝胶的抗菌活性和机械性能。Cu-rhein NSs 和 ZnO MSs 共修饰到由氧化海藻酸钠、明胶和硼砂构建的细胞外基质模拟的双网络智能水凝胶中，通过动态硼酸酯键和席夫碱键。该智能水凝胶具有良好的生物相容性，针对慢性难治性创面的独特酸性微环境和高氧化应激，智能释放仿生纳米酶，有效消除细菌、减轻炎症反应和清除多种自由基以减少 ROS。基于糖尿病感染的大鼠模型的体内实验表明，智能水凝胶能够有效消除细菌、促进血管再生和胶原沉积、减轻炎症反应，加速糖尿病感染创面的愈合（14 天内几乎完全愈合）。该智能仿生组织再生级联管理策略在糖尿病感染创面愈合方面的优势得到了强调。
