"A Versatile Chitosan-Based Hydrogel Accelerates Infected Wound Healing via Bacterial Elimination, Antioxidation, Immunoregulation, and Angiogenesis"

作者全名："Zhang, Ye; Chen, Sinan; Qin, Xian; Guo, Ai; Li, Kai; Chen, Lixue; Yi, Weiwei; Deng, Zhongliang; Tay, Franklin R.; Geng, Wenbo; Miao, Li; Jiao, Yang; Tao, Bailong"

作者地址："[Zhang, Ye; Chen, Sinan; Guo, Ai; Li, Kai; Chen, Lixue; Tao, Bailong] Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing 400016, Peoples R China; [Qin, Xian] Chongqing Med Univ, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Yi, Weiwei] Chongqing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, Chongqing 400016, Peoples R China; [Deng, Zhongliang] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing 400010, Peoples R China; [Tay, Franklin R.] Augusta Univ, Grad Sch, Augusta, GA 30912 USA; [Geng, Wenbo] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing 400016, Peoples R China; [Miao, Li; Jiao, Yang] Peoples Liberat Army Gen Hosp, Med Ctr 7, Dept Stomatol, Beijing 100700, Peoples R China"

通信作者："Tao, BL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing 400016, Peoples R China.; Geng, WB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing 400016, Peoples R China.; Miao, L; Jiao, Y (通讯作者)，Peoples Liberat Army Gen Hosp, Med Ctr 7, Dept Stomatol, Beijing 100700, Peoples R China."

来源：ADVANCED HEALTHCARE MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001178259800001

JCR分区：Q1

影响因子：10

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：angiogenesis; anti-inflammation; drug-resistant bacteria; immunomodulation; wound healing

摘要："Drug-resistant bacterial infection of cutaneous wounds causes great harm to the human body. These infections are characterized by a microenvironment with recalcitrant bacterial infections, persistent oxidative stress, imbalance of immune regulation, and suboptimal angiogenesis. Treatment strategies available to date are incapable of handling the healing dynamics of infected wounds. A Schiff base and borate ester cross-linked hydrogel, based on phenylboronic acid-grafted chitosan (CS-PBA), dibenzaldehyde-grafted poly(ethylene glycol), and tannic acid (TA), is fabricated in the present study. Customized phenylboronic acid-modified zinc oxide nanoparticles (ZnO) are embedded in the hydrogel prior to gelation. The CPP@ZnO-P-TA hydrogel effectively eliminates methicillin-resistant Staphylococcus aureus (MRSA) due to the pH-responsive release of Zn2+ and TA. Killing is achieved via membrane damage, adenosine triphosphate reduction, leakage of intracellular components, and hydrolysis of bacterial o-nitrophenyl-beta-d-galactopyranoside. The CPP@ZnO-P-TA hydrogel is capable of scavenging reactive oxygen and nitrogen species, alleviating oxidative stress, and stimulating M2 polarization of macrophages. The released Zn2+ and TA also induce neovascularization via the PI3K/Akt pathway. The CPP@ZnO-P-TA hydrogel improves tissue regeneration in vivo by alleviating inflammatory responses, stimulating angiogenesis, and facilitating collagen deposition. These findings suggest that this versatile hydrogel possesses therapeutic potential for the treatment of MRSA-infected cutaneous wounds. The ZnO-P nanoparticle embedded composite hydrogel is fabricated via Schiff base and borate ester cross-linked reaction. The CPP@ZnO-P-TA hydrogel presents pH-responsive release of Zn2+ and TA for killing methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, this hydrogel alleviates oxidative stress, stimulates M2 polarization of macrophages, and induces neovascularization via the PI3K/Akt pathway for MRSA-infected cutaneous wounds healing. image"

基金机构："National Natural Science Foundation of China; Natural Science Foundation of Chongqing Science and Technology Commission [cstc2021jcyj-msxmX0170, CSTB2022BSXM-JCX0039, CSTB2022BSXM-JCX0058]; Beijing Nova Program [20230484283]; Beijing Municipal Science and Technology Commission [Z221100007422130]; Beijing Municipal Natural Science Foundation [7242279]; Youth Incubation Program of Medical Science and Technology of PLA [21QNPY116]; First Affiliated Hospital of Chongqing Medical University cultivating fund [PYJJ2021-02, PYJJ2021-04]; [82102537]; [82101069]"

基金资助正文："Y.Z. and S.C. contributed equally to this work. This work was financially supported by the National Natural Science Foundation of China (Nos. 82102537 and 82101069), the Natural Science Foundation of Chongqing Science and Technology Commission (Nos. cstc2021jcyj-msxmX0170, CSTB2022BSXM-JCX0039, and CSTB2022BSXM-JCX0058), the Beijing Nova Program (No. 20230484283), the Beijing Municipal Science and Technology Commission (No. Z221100007422130), the Beijing Municipal Natural Science Foundation (No. 7242279), the Youth Incubation Program of Medical Science and Technology of PLA (No. 21QNPY116), and the First Affiliated Hospital of Chongqing Medical University cultivating fund (Nos. PYJJ2021-02 and PYJJ2021-04)."