Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
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IF 3.9
Tang Di,Lin Qiang,Li Pei-Wen,Wang Song,Xu Kai,Huang Yue-Sheng,Lu Qi-Ping
Chronic refractory wounds are a common, costly and recurrent complication of diabetes. Platelet-rich plasma (PRP), a new therapy for chronic wounds, is limited by a long treatment period and unstable effects. FG-4592(Roxadustat) is a new prolyl-4-hydroxylation domain(PHD) inhibitor, which can stabilize hypoxia-inducible factor-1α(HIF-1α) effectively. It is a promising drug for wound repair and needs to be demonstrated via various appropriate application scenarios. This study investigated the effects of combining FG-4592 and PRP to promote diabetic wound healing. Diabetic rats were randomly assigned to five groups: nondiabetic control, diabetic untreated, diabetic + PRP, diabetic + FG-4592, and diabetic + PRP + FG-4592. Diabetes was induced with streptozotocin (STZ). A full-thickness skin defect was created, and FG-4592 (peritoneal injection) and PRP (periwound injection) were administered alone or together. Wound healing was assessed by histological analysis (Hematoxylin-Eosin (HE) and Masson staining) and protein expression of HIF-1α, VEGF(vascular endothelial growth factor), α-SMA(α-smooth muscle actin), CoL1α1(collagen type 1 alpha 1), and SDF-1(Stromal Cell-derived Factor 1) via Western blotting and qRT-PCR(Quantitative real time polymerase chain reaction). Immunohistochemistry(IHC) and immunofluorescence(IF) were also used to evaluate CD34 (Cluster of Differentiation 34), CD31(Cluster of Differentiation 31), VEGF(vascular endothelial growth factor), SDF-1(Stromal Cell-derived Factor 1), PCNA(Proliferating Cell Nuclear Antigen), and Integrin-β1 expression. The untreated diabetic group exhibited impaired wound healing, histological damage, and reduced expression of key proteins compared to the nondiabetic control group. Both PRP and FG-4592 alone improved wound healing, reduced damage, and upregulated protein expression. However, the combination of FG-4592 and PRP showed the most significant improvement. This study suggests that FG-4592 combined with PRP accelerates diabetic wound healing by enhancing endothelial progenitor cell recruitment, neovascularization, and cell proliferation and migration via upregulation of HIF-1α and its target genes. This combination therapy may provide a novel approach for treating chronic diabetic wounds.
研究领域:
医学
·
分子生物学
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Junran Yang,Xinglong Liu,Yan Tang,Xiaoyu Bi,Huiying He,Xiaohang Sun,Qi Sui,Donglin Li,Wencong Liu,Dadong Liang,Chuanbo Ding
To avoid the problem of difficult wound healing caused by diabetes. In this study, zeolite imidazolium ester skeleton-8 (ZIF-8) was loaded with dihydroquercetin (DHQ) in order to improve the slow-release property as well as the biological activity of DHQ, and the mechanism of wound healing action of ZIF-8-loaded hydrogel was investigated by Western blot technique. The results showed that the dynamic light scattering result was 90.54 ± 3.45 nm and the zeta potential was −32.91 mV. In addition, through the synergistic effect of ZIF-8 and DHQ, the hydrogel exhibited excellent in vitro activity, and the in vitro antioxidant results showed that the inhibition rate of DZP hydrogel against the free radicals of ABTS and DPPH was over 90%, and the inhibition rate against Escherichia coli and Staphylococcus aureus was over 90%, respectively, and also promoted cell growth and migration. In addition, the in vitro release assay of DHQ from DZP hydrogel at 24 h showed 61.69 ± 1.93% at pH = 6.0 and 62.42 ± 1.58% at pH = 7.4, which improves the slow-release property of DHQ and is suitable for long-term tissue repair applications. The results of in vivo experiments showed that DZP hydrogel promotes the healing of difficult-to-heal wounds by inhibiting the activation of the IkBα/NF-κB pathway, stimulating skin neovascularisation, and promoting collagen accumulation. Collectively, these properties make DZP a strong candidate for diabetic wound dressings and are expected to play an important role in wound management.
研究领域:
材料科学
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生物医学
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药理学
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Ying Yin,Wentai Guo,Qiangyu Chen,Zhimin Tang,Zheng Liu,Ruibin Lin,Ting Pan,Jiezhao Zhan,Li Ren
Diabetic wound healing presents a significant medical challenge and requires multistep interventions due to comprehensive wound environments, such as hyperglycemia, bacterial infection, and impaired angiogenesis. However, current multistep interventions are complicated and need on-demand sequential release and synergy of multicomponents. Herein, a H2S-releasing cascade nanozyme (FeS@Au), which is composed of ultrasmall gold nanocluster (AuNC) loaded on ferrous sulfide nanoparticle (FeSNP), is developed as a single component to regulate glucose level, eliminate infection, and promote angiogenesis, achieving multistep interventions for comprehensive diabetic wound treatment. The glucose oxidase-like activity of AuNC catalyzes glucose into gluconic acid and H2O2, which not only lowers the local glucose level but also decreases the local pH and increases H2O2 level to boost the peroxidase-like activity of FeSNP to generate abundant hydroxyl radical (reactive oxygen species, ROS), inducing ferroptosis-like death in drug-resistant bacteria. Additionally, FeSNP release H2S in the acidified environment to upregulate hypoxia-inducible factor-1 to enhance vascularization through upregulating the expression of vascular endothelial growth factor (VEGF) and other angiogenesis-related genes, reducing the damage to endothelial cells caused by excessive ROS produced by the nanozyme. In a full-thickness MRSA-infected diabetic rat model, FeS@Au significantly eliminates bacteria, enhances angiogenesis, promotes collagen deposition, and accelerates wound healing. This work presents a single nanozyme with H2S-release for multistep interventions, providing a versatile strategy for healing extensive tissue damage caused by diabetes.
研究领域:
生物医学工程
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药理学
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纳米医学
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DOI
PubMed
高影响因子
Small
·
2024
·Vol. 20
·期 52
·2407802
·
IF 13
Mengyang Li,Yuhang Dong,Yage Shang,Jiaqi Liu,Yunchuan Wang,Dongliang Zhang,Lixia Zhang,Chao Han,Yue Zhang,Kuo Shen,Yaoxiang Yang,Hongtao Wang,Hao Guan,Dahai Hu
Excessive generation of reactive oxygen species (ROS) poses a huge obstacle to the healing process of diabetic wounds, resulting in chronic, non-healing wounds. While numerous anti-ROS therapeutics have been developed, satisfied intra- and extra- cellular ROS homeostasis is hard to be established in diabetic wounds. To address this issue, a nanoparticle via loading metformin and CeO 2 into mesoporous silica (MSN@Met-CeO 2 ) is designed and synthesized, which is then encapsulated within ROS-responsive hydrogel and shaped as microneedles (MNs) for better application in diabetic wounds. Interestingly, a unique metformin-cerium chelate (Ce· 3Metformin) is formed during the synthesis of MSN@Met-CeO 2 MN, which significantly strengthened the inhibitory effect of metformin on mitochondrial complex I. With the presence of Ce· 3Metformin, MSN@Met-CeO 2 MN performed a remarkable effect on intracellular mtROS reduction as well as extracellular ROS elimination, the latter is primarily accomplished through the dissociative CeO 2 in MSN@Met-CeO 2 MN. In the mouse diabetic wound model, MSN@Met-CeO 2 MN exhibited a superior pro-healing effect with accelerated inflammation resolution and enhanced angiogenesis, thus highlighting its significant potential for clinical application
研究领域:
医学
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生物材料学
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药理学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2025
·
IF 7.9
Hongyu Lv,Siyuan Wang,Mou He,Xue Zhu,Peng He,Ruochen Sun,Zitong Jia,Ziming Wang,Wenwen Zhao,Zhangfeng Zhong,Yantao Han
The development of innovative wound dressings that can accelerate diabetic wound healing and alleviate hypertrophic scar has aroused intensive attraction in the clinics. In this study, the nanofibrous wound dressings constructed with a blend of silk fibroin (SF) and poly-3-hydroxybutyric acid-co-3-hydroxyvaleric acid (PHBV) were designed and fabricated. Meanwhile, berberine (BBR) were loaded in the SF/PHBV nanofibers to enhance the pharmacological effects. Firstly, material characterisation and biological characteristics of SF/PHBV-BBR dressings were investigated. The addition of BBR didn’t change the mechanical properties and biocompatibility of SF/PHBV nanofiber dressings. Then in vitro experiment proved that SF/PHBV-BBR nanofiber dressings obviously decreased the releases of inflammatory factors TNF-ɑ and IL-6, inhibited inflammatory proteins COX-2 and iNOS expression, and also suppressed oxidative stress responses of activated macrophages. Subsequently, in vivo study showed that SF/PHBV-BBR nanofiber dressings with high dose of BBR significantly promoted the healing of diabetic wounds in mice by significantly enhancing wound closure rates, accelerating angiogenesis, and improving collagen matrix deposition. Additionally, SF/PHBV-BBR obviously alleviated scar hyperplasia in rabbit by inhibiting fibroblast activation mediated by transforming growth factor-β1 (TGF-β1)/Smad3 pathway. Our study offered a promising alternative dressing materials for the treatment of hard-to-heal diabetic wounds and hypertrophic scars.
研究领域:
生物材料学
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药理学
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医学工程
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产品关联
DOI
高影响因子
Polymers
·
2020
·Vol. 12
·期 3
·535
·
IF 3.426
Yang Yang,Yanyan Zhang,Yishu Yan,Qian Ji,Yutong Dai,Suyuan Jin,Yanxian Liu,Jinghua Chen,Liping Teng
The diabetic wounds do not heal easily in part because they are susceptible to infection due to environmental influences. Wound dressing is crucial to wound healing, as it can basically protect the wound from external damages and provide a suitable microenvironment for tissue regeneration. In this study, a double-layer membrane that consists of chitosan sponge and decellularized bovine amniotic membrane (dBAM) has been developed by freeze-casting method. The results showed that the porous structure of the sponge layer improved the performances of blood coagulation and swelling. The dense dBAM can optimize the mechanical property of wound dressing. In vitro studies revealed that the bilayer membrane had favorable biocompatible, especially for human foreskin fibroblast cells (HFF-1) cell adhesion and proliferation. Moreover, the full-thickness skin defects of diabetic model mice that treated with bilayer membrane showed over 80% closure in 8 days. Our findings imply that the double-layer dressing has great potentials to be used in diabetic patients.Keywords:chitosan;decellularized bovine amniotic membrane;diabetic wound healing;double-layer dressing
研究领域:
生物材料学
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医学工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Cong Rui,Deng Chengyu,Li Pengwei,Tang Yiwei,Hou Jinfan,Zhao Jiehui,Wang Qili,Chen Yingying,Tu Jiasheng,Jiang Xiqun,Jiang Lei
Diabetic wounds require continuous and coordinated modulation of the microenvironment concurrent with tissue regeneration, which remains a significant challenge. As a proof of concept, we herein propose to use dimeric copper peptide (D-CuP) for diabetic wound treatment. The D-CuP is synthesized and then incorporated into a reactive oxygen species (ROS)-responsive hydrogel matrix to improve therapeutic compliance, culminating in the formulation of G/D-CuP. Compared to monomer copper peptide (M-CuP), a wound healing agent, D-CuP exhibits multivalency, enhanced biological stability against proteases, and broad biological activities. Meanwhile, the hydrogel matrix, exhibiting ROS-scavenging capabilities, has been engineered to be an intelligent drug reservoir for wound-responsive release of D-CuP at the wound site while simultaneously attenuating inflammatory responses. Ultimately, the G/D-CuP group demonstrates superior therapeutic efficacy, achieving 97.2% closure of infected wounds.
研究领域:
生物材料
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再生医学
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药剂学
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生物化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2025
·
IF 4.3
Wen Li,Zihan Zhang,Biyu Zhou,Yang Chen,Weijia Shen,Naiting Kuai,Jin Li
Serious vascular dysfunction and recurrent bacterial infection are critical obstacles in diabetic wound healing. Developing novel therapeutic strategies is crucial to address these challenges. Endothelial cell-derived apoptotic bodies (H-Abs), a novel type of extracellular vesicles with anti-inflammation and pro-angiogenesis properties, show great potential for diabetic wound treatment. Herein, a sprayable and thermosensitive in-situ forming composite gel based on poloxamer 407 (P407) was fabricated for the delivery of H-Abs camouflaged manganese dioxide nanozymes (BM), termed BM@H-Abs/TSCG-P407. In vitro and in vivo studies demonstrated that BM@H-Abs/TSCG-P407 undergoes a rapid sol-to-gel transformation in response to wound temperature during spraying treatment, thereby effectively covering irregularly shaped wounds. The incorporated H-Abs-camouflaged BM (BM@H-Abs) can effectively accelerate endothelial cell proliferation and migration, normalize oxygen supply, scavenge reactive oxygen species (ROS) accumulation, inhibit bacterial growth, and eventually enhance the healing of infected wounds in diabetic mice. These results indicate that BM@H-Abs/TSCG-P407 is a promising candidate for the treatment of diabetic wounds.
研究领域:
生物医学工程
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药剂学
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Hai Liu,Hongxiang Mei,Hejin Jiang,Linli Jiang,Kaifeng Lin,Minwen Jiang,Ning Ding,Xiaojie Li,Ziqi Gao,Bin Liu,Wei Lin,Juan Li,Jiajing Zhou
Providing oxygen and preventing infection at wound sites are effective ways to heal diabetic chronic wounds. Inspired by natural lichens, a bioprinted biogenic hydrogel (BBH) containing microalgae and probiotics is developed for diabetic chronic wound therapeutics, which offers prolonged biogenetic oxygen supply by microalgae and infection inhibition by probiotics. The rational design of symbiotic BBH with customizable structure and microorganism composition enhances wound resilience against elevated glucose levels and hypoxia, leading to the increased migration ability of fibroblasts and the angiogenic potential of human umbilical vein endothelial cells. Notably, BBH-treated diabetic wounds exhibit dense vascular distribution, reduced hypoxia levels and inflammatory responses, and enhanced epithelial differentiation and keratinization abilities. Consequently, the BBH achieves rapid tissue repairing within 3 d and restores approximately 90% of the whole skin structure within 12 d. This work presents an engineered platform for regulating biological microenvironment of diabetic wounds and provides insights for developing bioprinted hybrid microorganism systems.
研究领域:
生物医学工程
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再生医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Jiaying Zhang,Sifang Zhao,Yifan Zhou,Hongze Liang,Lingling Zhao,Hui Tan
Diabetic wound healing is hampered due to oxidative stress, exacerbated inflammation, and impaired angiogenesis in the wounds. A pH-sensitive antioxidant hydrogel based on carboxymethyl chitosan (CMCS), oligoprocyanidins (OPC), and oxide dextran (Oxd) is prepared to accelerate diabetic wound healing. The hydrogel network is formed via imine and hydrogen bonding interactions in the presence of hydroxyl, amino, and aldehyde groups, and deferoxamine (DFO) is incorporated into the hydrogel. The hydrogel shows pH-triggered drug release, a good antioxidant, and anti-inflammatory properties, and can promote tube formation and cell migration in vitro. Moreover, the hydrogel can accelerate wound healing in streptozotocin (STZ)-induced diabetic mice by regulating the inflammation environment with up-regulation of anti-inflammatory factors (IL-4 and IL-10) and down-regulation of pro-inflammatory factors (TNF-α and IL-6), and promoting angiogenesis with up-regulation of HIF-1α, VEGF, and CD31. Thus, the pH-sensitive antioxidant hydrogel provides a promising therapeutic strategy for diabetic wound healing.
研究领域:
生物材料学
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医学
·
药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Xu Liu,Xiao Han,Yushuang Shang,Lijuan Wang,Jian Shen,Jiang Yuan
Adverse factors such as high levels of glucose, oxidative stress , inflammation, and bacterial infection impede diabetic wound healing and even worsen wounds. Owing to its outstanding anti-inflammatory and antioxidant properties as well as the potential to promote cell migration and proliferation, hydrogen sulfide(H 2 S) gas therapy is promising for chronic diabetic wound recovery. In this work, a multifunctional poly(γ-glutamic acid)(PGA) hydrogel encapsulated with keratin-based H 2 S donor(KTC), ciprofloxacin(Cip), and anthocyanins(Ant) was developed. The resultant hydrogel was capable of releasing H 2 S, thereby promoting cell proliferation and enhancing anti-inflammation and antioxidant activity . The release of antibiotic Cip was accelerated under a diabetic wound microenvironment, thereby enhancing the antibacterial activity of the hydrogel. The encapsulated Ant could serve as a pH monitor, sensitively indicating wound pH conditions in situ and indirectly reflecting wound infection. In vivo results in diabetic wound healing suggested that PGA/Ant/KTC/Cip hydrogel reduced inflammation and promoted angiogenesis and collagen deposition, thereby accelerating wound healing.
研究领域:
生物材料学
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药剂学
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医学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2025
·
IF 6
Zini Huang,Yihan Ma,Xinyi Yang,Xiaoping Yang,Yinjia Cheng,Aiqing Zhang
Persistent microbial infections and excessive reactive oxygen species (ROS) accumulation severely impede diabetic wound healing. Herein, we developed an ultrasound-switchable BiVO 4 /fullerene piezoelectric heterostructure via a one-pot solvothermal method, enabling on-demand transition between bactericidal action and ROS scavenging for treating infected diabetic wounds. Under 8-min ultrasound (US) irradiation, the heterojunction sonosensitizer leveraged piezoelectric polarization to generate substantial ROS in real-time through a narrowed energy band gap and enhanced charge carrier separation and migration efficiency, resulting in the disruption of bacterial membrane integrity and 99.9 % eradication of methicillin-resistant Staphylococcus aureus (MRSA). Upon US withdrawal, the sonosensitizer spontaneously transitioned to an antioxidative state through fullerene-mediated ROS scavenging, effectively neutralizing excess ROS and restoring cellular redox balance. In an MRSA-infected diabetic wound model, this ultrasound-responsive duality effectively suppressed bacterial proliferation, reduced inflammation, enhanced angiogenesis, and ultimately accelerated wound healing within 14 days. This ultrasound-switchable therapeutic strategy offers promising insights for managing drug-resistant infections and other ROS-mediated biomedical challenges.
研究领域:
生物医学工程
·
材料科学
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微生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）