Double hits with bioactive nanozyme based on cobalt-doped nanoglass for acute and diabetic wound therapies through anti-inflammatory and pro-angiogenic functions  

作　　者：Nandin Mandakhbayar YunSeong Ji Ahmed El-Fiqi Kapil DPatel Dong Suk Yoon Khandmaa Dashnyam Oyunchimeg Bayaraa Gangshi Jin Khaliunsarnai Tsogtbaatar Tae-Hyun Kim Jung-Hwan Lee Hae-Won Kim 

机构地区：[1]Institute of Tissue Regeneration Engineering(ITREN),Dankook University,Cheonan,31116,Republic of Korea [2]Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine,Dankook University,Cheonan,31116,Republic of Korea [3]Glass Research Department,National Research Centre,Cairo,12622,Egypt [4]School of Cellular and Molecular Medicine(CMM),University of Bristol,Bristol,BS81TD United Kingdom [5]Department of Biomedical Science,Hwasung Medi-Science University,Hwaseong-Si 18274,Gyeonggi-Do,Republic of Korea [6]Drug Research Institute,Mongolian University of Pharmaceutical Sciences,Ulaanbaatar 14250,Mongolia [7]R&D Center,TE Bios,Osong,Republic of Korea [8]Department of Biomaterials Science,School of Dentistry,Dankook University,Cheonan,31116,Republic of Korea [9]Mechanobiology Dental Medicine Research Center,Dankook University,Cheonan,31116,Republic of Korea [10]UCL Eastman-Korea Dental Medicine Innovation Centre,Dankook University,Cheonan,31116,Republic of Korea [11]Cell&Matter Institute,Dankook University,Cheonan 31116,Republic of Korea

出　　处：《Bioactive Materials》2024年第1期298-311,共14页生物活性材料（英文）

基　　金：supported by the National Research Foundation of Korea(2021R1A5A2022318,2018K1A4A3A01064257,2019R1A6A1 A11034536,RS-2023-00220408,2022K1A3A1A08085419,2021R1I1 A1A01049104).

摘　　要：Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events.This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass(namely,CoNZ),which exhibits high enzymatic/catalytic activity while releasing therapeutic ions.Cobalt oxide“Co3O4”tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS.Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process,promoting neovascularization,matrix deposition,and epithelial lining while reducing pro-inflammatory signs.Notably,CoNZ was highly effective in treating pathological wounds(streptozotocin-induced diabetic wounds).Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events.In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ.CoNZ-promoted angiogenesis was attributed to the release of cobalt ions,as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α.Finally,we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine.Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound,indicating the potential of CoNZ as a novel drug-free therapeutic approach.

关 键 词：Diabetic wound Nanozyme ANTI-INFLAMMATION Angiogenesis Therapeutic materials 

分 类 号：TB383[一般工业技术—材料科学与工程]