INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Zixuan Wang,Yingxiao Sun,Peijie Dong,Jinhu Wang,Lijie Wang,Aili Zhao,Guangmin Qu,Hang Li,Kannapathirage Dilini Maheshika Gunarathne,Wen Zhang,Yao Chen,Xin Meng
Trauma healing is the process of healing after the body has been subjected to an external force and the skin and other tissues have become dissected or defective, showing the synergistic effect of various processes. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we constructed a zinc based metal–organic framework (MOF) and loaded with antimicrobial peptide LL37 to prepare LL37@ZPF-2 (ZPF = zeolite pyrimidine backbone), which was subsequently integrated with Poloxamer 407 to fabricate LL37@ZPF-2 thermosensitive hydrogel. Our study showed that in-situ packaging method can achieve encapsulation rate of 98 % and 15 % of drug loading for LL37. LL37@ZPF-2 demonstrated a higher inhibitory potency against S.aureus compared to E.coli . The Poloxamer 407-gel exhibits thermo-responsive sol–to–gel phase transition behaviors with a phase transition temperature (Tsol/gel) of ∼ 28.01℃, making it an appropriate material for wound healing. The composite hydrogel has excellent biocompatibility and hemocompatibility. A full-thickness skin defect model was built to confirm that LL37@ZPF-2 thermosensitive hydrogel dressing could inhibit bacterial growth, reduce the risk of wound infection, and stimulate angiogenesis and collagen deposition, resulting in a wound healing rate of 94.4 % on day 7 and complete healing on day 10. Our findings demonstrate that the novel thermosensitive LL37@ZPF-2 hydrogel confers good antibacterial activity, promoting cell migration and infected-wound healing properties, providing a promising platform for wound healing.
研究领域:
生物医学工程
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药剂学
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伤口愈合
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抗菌研究
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材料科学
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DOI
PubMed
高影响因子
Materials Today Bio
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2024
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IF 8.7
Fei Li,Chuwei Zhang,Xiaoping Zhong,Bo Li,Mengnan Zhang,Wanqian Li,Lifei Zheng,Xinghua Zhu,Shixuan Chen,Yi Zhang
Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.
研究领域:
生物医学工程
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伤口愈合
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组织工程
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感染控制
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Pei Liu,Mengna Li,Hongping Yu,Haoyu Fang,Junhui Yin,Daoyu Zhu,Qianhao Yang,Qinfei Ke,Yigang Huang,Yaping Guo,Youshui Gao,Changqing Zhang
Articular osteochondral defect is commonly seen after trauma or in patients with degenerative osteoarthritis. Currently, the treatment of osteochondral lesions is still challenging due to the limited healing ability of cartilage as well as the poorly effective traditional method. In this study, we fabricated a bilayer peptide-loaded scaffold consisting of CK2.1 coated β-glycerophosphate/chitosan ( [email protected] ) for cartilage regeneration and LL37 modified layered double hydroxide/chitosan ( [email protected] ) for subchondral bone regeneration, designed in an integrated strategy involving mesenchymal stem cells (MSCs) recruitment and multifunctional therapeutic biomaterials of bone regeneration and vascularization. The lower LC scaffold is highlighted with a biomimetic lamellar structural design, providing a novel platform for the integration of newborn bone tissue and blood vessels. In vitro results showed our peptide-loaded bilayer scaffold could induce the MSCs to differentiate into chondrocytes and osteoblasts in different layers respectively. [email protected] could also attract MSCs and promote vasculogenesis in vitro. Meanwhile, osteochondral defect could be efficiently repaired by this peptide-modified bilayered scaffold in the rabbit model. This study demonstrated that our composite scaffold could smartly enhance the repair of hyaline cartilage and subchondral bone defect, which shed light on a novel therapeutic strategy for the intervention of patients with articular osteochondral defect.
研究领域:
组织工程
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再生医学
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生物材料科学
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骨科
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DOI
高影响因子
Materials Today Bio
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2025
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IF 10.2
Yushuang Wei,Wenwen Li,Rong Xu,Cheng Xu,Xiangyang Li,Ning Li,Fengdan Xu,Kai Yang,Bing Yuan
Recent studies have demonstrated that the human antimicrobial peptide LL37 plays a critical role in immune regulation under both normal physiological conditions and during disease progression, as evidenced by its elevated levels observed in various chronic inflammatory diseases. A deeper understanding of its mechanism is essential for elucidating associated physiological and pathological processes, as well as for designing effective immune adjuvants and clinical therapeutics. In this study, we report that LL37 facilitates the assembly of unmethylated CpG dinucleotides (CpG ODNs), a clinically relevant immune adjuvant, into non-crystalline nanoparticles (NPs) with controlled size and zeta potential in a charge ratio-dependent manner. These assembled NPs enter cells via receptor-mediated macropinocytosis, coupled with LL37-mediated membrane penetration, thereby significantly enhancing cellular uptake of CpG compared to CpG alone, which enters cells through clathrin-mediated endocytosis. Consequently, the enhanced internalization of LL37-CpG NPs markedly boosts TNF-α production (>3.5-fold) in macrophages through interactions with lysosomal TLR9. This immunostimulatory mechanism offers an alternative perspective on how LL37 modulates nucleic acid assembly and activates immune cells, providing guidance for the application of peptide-CpG ODN complexes in vaccine adjuvants and immune modulation for disease treatment.
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PubMed
高影响因子
Science Advances
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2020
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IF 13.117
Huiyi Liang,Yanzi Yan,Jingjiao Wu,Xiaofei Ge,Lai Wei,Lixin Liu,Yongming Chen
Cell-free DNA (cfDNA) released from damaged or dead cells combines with LL37 and is converted into an immune response activator to exacerbate psoriasis. Here, we show that cationic nanoparticles (cNPs) efficiently compete for DNA from the DNA-LL37 immunocomplex and inhibit DNA-LL37-induced cell activation. Using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cNPs on psoriasiform skin of a mouse model relieves psoriatic symptoms. It is noteworthy that the results were confirmed in a cynomolgus monkey model. Moreover, topically administrated cNPs showed low in vivo toxicity because of their retention in skin. Mechanistic analyses of cytokine expression in the psoriatic site, cfDNA levels in circulation and inflamed skin, skin permeation, and biodistribution of cNPs also matched the therapeutic outcomes. Therefore, we present a previously unidentified strategy of nanomedicine to treat skin inflammatory diseases, which demonstrates great potential for clinical application.
研究领域:
药学
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免疫学
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皮肤病学
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纳米技术
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临床前研究
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Lijie Wang,Zixuan Wang,Jiarong Chang,Zhiyue Zhou,Xihan Wang,Zhaoming Li,Dawei Li,Fang Wang,Wen Zhang,Kannapathirage Dilini Maheshika Gunarathne,Xin Meng
Infected skin wound healing involves a series of dynamic and complex physiological processes. In this study, we reported a dissolvable microneedle (MN) with pullulan as the matrix material. The antimicrobial peptide LL37 was immobilized in situ within ZIF-8 to form hybrid nanoparticle LL37@ZIF-8 (LZ). This nanoparticle was then loaded onto the tip of the microneedle along with Prussian Blue (PB) nanozymes to obtain PB+LZ@MN, which exhibits both antimicrobial and antioxidative activities, for the healing of infected skin wounds. The MN, with good mechanical properties, could rapidly dissolve its tip upon insertion into the skin, releasing LZ and PB into the wound within 3 min. The MN had good physicochemical properties and biocompatibility and was shown to reduce inflammation and stimulate angiogenesis by enhancing collagen deposition and re-epithelialization in the Sprague-Dawley (SD) rat skin defect infection model. On the 10th day of wound healing, the healing rate of the PB+LZ@MN group was as high as 99%, which was significantly higher than that of the control at 84%, significantly accelerating the healing of the infected wound. This multifunctional MN is expected to provide a competitive biomaterial for accelerated infected wound healing.
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PubMed
高影响因子
INFLAMMATION
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2024
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IF 4.5
Yuan Xin,Sheng Liang,Shi Guang,Jiang Leiwei,Lian Chengxiang
Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro , RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1β, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo . Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.
研究领域:
皮肤科
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Pengyu He,Dawei Wang,Ruizhu Zheng,Hao Wang,Lina Fu,Guoliang Tang,Zhijun Shi,Yiping Wu,Guang Yang
Infection-associated complications and repair failures and antibiotic resistance have emerged as a formidable challenge in hernia repair surgery. Consequently, the development of antibiotic-free antibacterial patches for hernia repair has become an exigent clinical necessity. Herein, a GBC/Gel/LL37 biological patch (biopatch) with exceptional antibacterial properties is fabricated by grafting 2-Methacryloyloxyethyl trimethylammonium chloride (METAC), a unique quaternary ammonium salt with vinyl, onto bacterial cellulose (GBC), followed by compounding with gelatin (Gel) and LL37. The GBC/Gel/LL37 biopatch exhibits stable swelling capacity, remarkable mechanical properties, flexibility, and favorable biocompatibility. The synergistic effect of METAC and LL37 confers upon the GBC/Gel/LL37 biopatch excellent antibacterial efficacy against Staphylococcus aureus and Escherichia coli , effectively eliminating invading bacteria without the aid of exogenous antibiotics in vivo while significantly reducing local acute inflammation caused by infection. Furthermore, the practical efficacy of the GBC/Gel/LL37 biopatch is evaluated in an infected ventral hernia model, revealing that the GBC/Gel/LL37 biopatch can prevent the formation of visceral adhesions, facilitate the repair of infected ventral hernia, and effectively mitigate chronic inflammation. The prepared antibacterial GBC/Gel/LL37 biopatch is very effective in dealing with the risk of infection in hernia repair surgery and offers potential clinical opportunities for other soft injuries, exhibiting considerable clinical application prospects.
研究领域:
生物医学工程
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材料科学
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外科研究
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组织工程
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抗菌技术
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
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IF 5.8
Jingyu He,Chen Wang,Gan Lin,Xiao Xia,Hangping Chen,Zhiyuan Feng,Zhengwei Huang,Xin Pan,Xuejuan Zhang,Chuanbin Wu,Ying Huang
The diabetic wound is a prevalent and serious complication of diabetes, which easily deteriorates due to susceptibility to infection and difficulty in healing, causing a high risk of amputation and economic burden to patients. Bacterial infection, persistent excessive inflammation, and cellular and angiogenesis disorders are the main reasons for the difficulty of diabetic wound healing. In this study, glycerol monooleate (GMO) was used to prepare lyotropic liquid crystal hydrogel (LLC) containing the natural antimicrobial peptide LL37 and carbenoxolone (CBX) to achieve antibacterial, anti-inflammation, and healing promotion for the treatment of diabetic wounds. The shear-thinning properties of the LLC precursor solution allowed it to be administered in the form of a spray, which perfectly fitted the shape of the wound and transformed into a gel after absorbing wound exudate to act as a wound protective barrier. The faster release of LL37 realized rapid sterilization of wounds, controlled the source of inflammation, and accelerated wound healing. The inflammatory signaling pathway was blocked by the subsequently released CBX, and the spread of the inflammatory response was inhibited and then further weakened. In addition, CBX down-regulated connexin (Cx43) to assist LL37 to promote cell migration and proliferation better. Combined with the pro-angiogenic effect of LL37, the healing of diabetic wounds was significantly accelerated. All these advantages made LL37-CBX-LLC a promising approach for the treatment of chronic diabetic wounds.
研究领域:
药学
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材料科学
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生物医学工程
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
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