Center for Advanced Low-dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201600, China.
School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, 201203, China.
Biomaterials. 2022 Oct;289:121790. doi: 10.1016/j.biomaterials.2022.121790. Epub 2022 Sep 5.
Diabetes immunity-modulated wound treatment in response to the varied microenvironments at different stages remains an urgent challenge. Herein, glucose oxidase (GOx) and quasi-amorphous FeO are co-incorporated into Zn-MOF nanoparticle (F-GZ) for cascade enzyme catalytic activities, where not only the high blood glucose in the wound is consumed via the GOx catalysis, but also the effective anti-bacteria is achieved via the degradedly released Zn synergistically with the catalytically produced ·OH during the bacterial infection period with the low pH microenvironment. Simultaneously, the reactive oxygen species scavenging and hypoxia relief is realized via catalyzing HO to produce O at the relatively elevated pH environment during the wound recovery period. Subsequently, a multifunctional hydrogel with injectable, self-healing and hemostasis abilities, as well as uniformed F-GZ loading is prepared via the copolymerization reaction. This hydrogel behaves as F-GZ but reduces the toxic effects, which thus accelerates the diabetic wound healing. More importantly, this hydrogel is found to modulate the diabetes immunity possibly mediated via the released Zn, which thus contributes to the recovered pancreatic islet functions with improved glucose tolerance and increased insulin secretion for enhanced diabetic wound treatments. This work initiates a new strategy for simultaneous diabetic wound management and also suggests a potential way for diabetic immunity modulation.
针对不同阶段的多样化微环境,糖尿病免疫调节性伤口治疗仍然是一个迫切的挑战。在此,葡萄糖氧化酶(GOx)和类非晶态 FeO 被共掺入 Zn-MOF 纳米颗粒(F-GZ)中以实现级联酶催化活性,其中不仅通过 GOx 催化消耗伤口中的高血糖,而且还通过在低 pH 微环境中的细菌感染期间与催化产生的·OH 协同作用,有效抗菌。同时,通过催化 HO 在伤口恢复期间相对升高的 pH 环境中产生 O 来实现清除活性氧和缓解缺氧。随后,通过共聚反应制备了一种具有可注射、自修复和止血能力以及均匀 F-GZ 负载的多功能水凝胶。该水凝胶表现为 F-GZ,但减轻了毒性作用,从而加速了糖尿病伤口的愈合。更重要的是,发现这种水凝胶可能通过释放的 Zn 来调节糖尿病免疫,从而有助于恢复胰岛功能,提高葡萄糖耐量和增加胰岛素分泌,从而增强糖尿病伤口的治疗效果。这项工作为同时进行糖尿病伤口管理开创了一种新策略,并为糖尿病免疫调节提供了一种潜在的方法。