Zhendong Li , Longhui Chen , Shasha Yang , Jinzhi Han , Yunquan Zheng , Zelong Chen , Xianai Shi , Jianmin Yang
{"title":"具有抗菌、清除活性氧和血管生成特性的葡萄糖和 pH 双响应水凝胶,可促进感染性糖尿病足溃疡的愈合。","authors":"Zhendong Li , Longhui Chen , Shasha Yang , Jinzhi Han , Yunquan Zheng , Zelong Chen , Xianai Shi , Jianmin Yang","doi":"10.1016/j.actbio.2024.10.020","DOIUrl":null,"url":null,"abstract":"<div><div>The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO<sub>2</sub>NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>Escherichia coli</em>. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO<sub>2</sub>NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot.</div></div><div><h3>Statement of Significance</h3><div>Here, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O<sup>2-</sup>, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>E. coli</em>. Additionally, <em>in vivo</em> experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 205-218"},"PeriodicalIF":9.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers\",\"authors\":\"Zhendong Li , Longhui Chen , Shasha Yang , Jinzhi Han , Yunquan Zheng , Zelong Chen , Xianai Shi , Jianmin Yang\",\"doi\":\"10.1016/j.actbio.2024.10.020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO<sub>2</sub>NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>Escherichia coli</em>. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO<sub>2</sub>NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot.</div></div><div><h3>Statement of Significance</h3><div>Here, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O<sup>2-</sup>, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>E. coli</em>. Additionally, <em>in vivo</em> experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.</div></div>\",\"PeriodicalId\":237,\"journal\":{\"name\":\"Acta Biomaterialia\",\"volume\":\"190 \",\"pages\":\"Pages 205-218\"},\"PeriodicalIF\":9.4000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Biomaterialia\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1742706124006123\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Biomaterialia","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1742706124006123","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers
The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO2NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO2NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot.
Statement of Significance
Here, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O2-, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.
期刊介绍:
Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.