Yang Yilei, Ding Dejun, Huang Changbao, Ding Xinghua, Wang Tao, Zhuo Mengting, Wang Huijuan, Kai Shuangshuang, Cheng Ni
College of Pharmacy, Shandong Second Medical University, Weifang, Shandong 261053, PR China.
College of Pharmacy, Shandong Second Medical University, Weifang, Shandong 261053, PR China.
J Colloid Interface Sci. 2025 Aug;691:137401. doi: 10.1016/j.jcis.2025.137401. Epub 2025 Mar 20.
Diabetic wounds tend to develop into non-healing wounds associated with a complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. This study developed a multifunctional hydrogel system by integrating aminoguanidine and hydrogen and oxygen gas-release nanoparticles (PAP NPs) into phenylboronic acid-modified quaternized chitosan and an oxidized dextran network. Hollow mesoporous Prussian blue (HPB) nanozymes with superoxide dismutase- and catalase-like activities are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous hydrogen peroxide (HO) into oxygen in diabetic wounds. Simultaneously, incorporating ammonia borane (AB)-loaded HPB NPs served as a source of hydrogen, further reducing ROS overproduction and modulating pro-inflammatory cytokine responses. Aminoguanidine in the hydrogel network inhibits the formation of advanced glycation end products (AGEs), inhibiting skin cell apoptosis and promoting their proliferation and migration. Moreover, the hydrogel exhibited significant mechanical characteristics and self-healing capacity owing to the Schiff base and phenylboronate ester linkages. Incorporating PAP NPs into the hydrogel produced an exceptional photothermal response, effectively eradicating bacteria with a mortality rate exceeding 95 % within 10 min and protecting the wound from potential infections. In vivo studies demonstrated that PAP@Gel significantly accelerated the healing of infected diabetic wounds by mitigating oxidative stress, enhancing oxygenation, inhibiting inflammation and AGE formation, and reversing bacterial infections. This study highlights a promising nanomedicine approach for designing future diabetic wound dressings, providing a novel strategy for catalytic ROS scavenging and synergistic hydrogen and oxygen therapies.
糖尿病伤口往往会发展成不愈合伤口，伴有难以控制的细菌感染、活性氧（ROS）积累和慢性缺氧等复杂的炎症微环境。本研究通过将氨基胍与氢气和氧气释放纳米颗粒（PAP NPs）整合到苯硼酸修饰的季铵化壳聚糖和氧化葡聚糖网络中，开发了一种多功能水凝胶系统。具有超氧化物歧化酶和过氧化氢酶样活性的中空介孔普鲁士蓝（HPB）纳米酶是很有前景的生物反应器，可通过将糖尿病伤口中升高的内源性过氧化氢（HO）转化为氧气，同时减轻ROS积累和缺氧。同时，掺入负载氨硼烷（AB）的HPB NPs作为氢源，进一步减少ROS的过度产生并调节促炎细胞因子反应。水凝胶网络中的氨基胍抑制晚期糖基化终产物（AGEs）的形成，抑制皮肤细胞凋亡并促进其增殖和迁移。此外，由于席夫碱和硼酸酯键，水凝胶表现出显著的机械特性和自愈能力。将PAP NPs掺入水凝胶中产生了出色的光热响应，能在10分钟内有效根除细菌，死亡率超过95%，并保护伤口免受潜在感染。体内研究表明，PAP@Gel通过减轻氧化应激、增强氧合作用、抑制炎症和AGE形成以及逆转细菌感染，显著加速了感染性糖尿病伤口的愈合。本研究突出了一种用于设计未来糖尿病伤口敷料的有前景的纳米医学方法，为催化ROS清除和协同氢氧疗法提供了一种新策略。
