Pharmaceutics
·
2022
·Vol. 15
·期 1
·88
·
IF 6.525
Xialin Li,Xingyu Huang,Long Li,Jiayi Wu,Weihong Yi,Yuxiao Lai,Lei Qin
Increased multiantibiotic-resistant bacteria means that infected bone defects remain a significant challenge to clinics. Great interest has emerged in the use of non-antibiotic antimicrobials to reduce the rate of multiantibiotic-resistant bacterial infection and facilitate bone regeneration. The cationic antimicrobial peptide LL-37 is the sole human cathelicidin and has shown nonspecific activity against a broad spectrum of microorganisms. In this study, we fabricated the poly(lactic-co-glycolic acid)/β-calcium phosphate/peptide LL-37 (PLGA/TCP/LL-37, PTL) scaffold with low-temperature 3D-printing technology for the treatment of infected segmental bone defects. The prepared scaffolds were divided into three groups: a high LL-37 concentration group (PTHL), low LL-37 concentration group (PTLL) and blank control group (PT). The cytocompatibility and antimicrobial activity of the engineered scaffolds were tested in vitro, and their osteogenesis properties were assessed in vivo in a rat infected bone defect model. We found the fabricated PTL scaffold had a well-designed porous structure that could support a steady and prolonged LL-37 release. Furthermore, the PTHL group showed strong antibacterial activity againstStaphylococcus aureus(S. aureus) andEscherichia coli(E. coli) without any inhibition of the proliferation or alkaline phosphatase activity of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. In addition, the infected femoral defects implanted with PTHL group displayed new bone formation in four weeks without any evidence of residual bacteria, which showed similar antibacterial outcomes to the vancomycin and cancellous bone mixture group. In conclusion, the PTHL composite scaffold is a promising non-antibiotic antimicrobial graft with good biodegradability, biocompatibility, and osteogenic capability for infected bone defects.Keywords:peptide LL-37;non-antibiotic antimicrobial graft;PLGA/TCP/LL-37 scaffolds;low-temperature 3D-printing technology;rat infected femoral defect model
研究领域:
生物材料
·
组织工程
·
骨科
·
生物医学工程
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传染病学
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2022
·Vol. 17
·期 4
·045025
·
IF 4.103
Mingchao Jin,Juli Zhu,Zhipeng Meng,Xuesheng Jiang,Zhuo Chen,Juntao Xu,Hongliang Gao,Junkun Zhu,Fengfeng Wu
Titanium dioxide (TiO2), as one of the titanium (Ti)-based implants, holds a promise for a variety of anti-bacterial application in medical research. In the current study, a functional molybdenum disulfide (MoS2)/polydopamine (PDA)-LL-37 coating on titanium dioxide (TiO2) implant was prepared. Anodic oxidation and hydrothermal treatment was given to prepare TiO2 nanotubes-MoS2/PDA-LL-37 (T-M/P-L). The in vitro osteogenic effect of T-M/P-L was evaluated by measuring mesenchymal stem cell (MSC) adhesion, proliferation, alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization, collagen secretion and osteoblast-specific messenger RNAs (mRNAs) expression. The determination on the anti-bacterial ability of T-M/P-L was followed. Furthermore, the ability of T-M/P-L to promote bone formation in vivo was evaluated. Near-infrared (NIR) laser irradiation exposure enabled the T-M/P-L coating-endowed Ti substrates to hold effective anti-bacterial ability. T-M/P-L promoted the adhesion and proliferation of MSCs. In addition, an increase was witnessed regarding the ALP activity, collagen secretion and ECM mineralization, along with the expression of runt-related transcription factor 2, ALP and osteocalcin in the presence of T-M/P-L. Additionally, T-M/P-L could stimulate endothelial cells to secrete vascular endothelial growth factor (VEGF) and promote capillary-like tubule formation. Upon NIR laser irradiation exposure, T-M/P-L not only exhibited efficient in vivo anti-bacterial activity but also facilitated new bone formation. Collectively, T-M/P-L had enhanced anti-bacterial and osteogenic activity under NIR laser irradiation.
研究领域:
生物材料
·
生物医学工程
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组织工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Peng Ye,Yusheng Yang,Ying Qu,Wenxin Yang,Jiulin Tan,Chengmin Zhang,Dong Sun,Jie Zhang,Weikang Zhao,Shuquan Guo,Lei Song,Tianyong Hou,Zehua Zhang,Yong Tang,Nathachit Limjunyawong,Jianzhong Xu,Shiwu Dong,Ce Dou,Fei Luo
This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus ( S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa ). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.
研究领域:
组织工程
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生物材料
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生物医学工程
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骨科
·
微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Ye He,Caiyun Mu,Xinkun Shen,Zhang Yuan,Ju Liu,Weizhen Chen,Chuanchuan Lin,Bailong Tao,Bin Liu,Kaiyong Cai
Titanium (Ti) and Ti-alloys were widely used in clinic orthopedics, however, the insufficient bone formation surrounding Ti-based implants still limited their biological performances. Surface modification of Ti substrates is essential to improve their interactions with bone-forming cells and bone tissue. In this study, we modified Ti substrates by coating peptide LL-37 onto micro-structured Ti substrates and aimed to (i) induce mesenchymal stem cells (MSCs) migration both in vitro and in vivo , (ii) facilitate osteogenic differentiation of MSCs and new bone formation. The surface micro-structured Ti substrates with hydroxyapatite deposition were fabricated by a two-step method including micro-arc oxidation (MAO) and hydrothermal treatment. LL-37 was loaded on micro-structured Ti substrates with the assistance of polydopamine coating. We confirmed that surface-modified Ti substrates benefited viability, adhesion, migration and osteogenic differentiation of MSCs in vitro . In a femur-defect rat model, the surface-modified Ti implants effectively induced CD29 + /CD90 + positive cells migration in one week after implantation. According to the results of H&E, Masson’s trichrome staining and immunohistochemical staining of OCN , OPN and collagen I, the targeted Ti implants exhibited significant new bone formation after implantation for 4 weeks. These results indicate that the surface modification of Ti samples facilitated bone formation through MSCs recruitment. Statement of Significance The inherent surface bioinertness of titanium (Ti) and Ti-alloys still limits their biological performances in clinical applications. Recently, the strategy of mesenchymal stem cells (MSCs) recruitment has been proposed to improve the osteointegration of bone implants. Herein, we reports the surface modification of Ti implants from the point of MSCs recruitment. Peptide LL-37 was coated on micro-structured Ti substrates to (i) recruit MSCs, (ii) regulate bio-physiological performance of MSCs, and (iii) facilitate bone formation in vivo. Our results improve the understanding of the interaction between Ti implants and MSCs, and provide a promising strategy of MSCs recruitment in the design of bone repair related biomaterials.
研究领域:
生物材料
·
组织工程
·
骨科
·
干细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Luogen Lai,Wanqing Zou,Yan Zhang,Yuanbiao Tu,Simeng Li,Tongxuan Xin,Tianyue Zhou,Shan Xu,Pengwu Zheng,Qingshan Pan,Wufu Zhu
Bacterial infections and antibiotic resistance have become a global healthcare crisis. There is an urgent need to develop visualized therapeutic platforms that allow accurate imaging of the bacterial infections, successful eradication of bacteria and real-time monitoring of treatment progress. In this work, we report a novel NIR imaging and synergistic antibacterial nano-system ( [email protected] ) for resistance bacterial infection therapy. The multifunctional nano-system is fabricated by a MIL-101 core, which is covalently connected with Vancomycin and modified with targeted antimicrobial peptides LL-37 on the surface. The ability of monitoring the progress of infection treatment and effective promoting wound healing of bacterial infection are proved by in vivo MRSA -infected mice models. Under the environment of endogenous H 2 O 2 overexpression and slightly acid bacterial infection, the excellent Fenton-like reaction activity of [email protected] could effectively catalyze the decomposition of H 2 O 2 to produce hydroxyl radicals (•OH), which trigger highly efficient chemo-dynamic therapy (CDT) and tissue protection effect. By combining CDT with antibacterial peptides and antibiotics therapy, special targeting and synergistic killing of MRSA are successfully achieved in in vitro and in vivo antibacterial assays with excellent biocompatibility. Due to this, this study proposes a novel, high-efficient, multifunctional imaging and therapy system, which will open a new avenue for the design of synergistic antibacterial and diagnostic platforms in the future.
研究领域:
纳米技术
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药学
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生物医学工程
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传染病学
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材料科学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Shue Jin,Renli Yang,Chen Hu,Shiqi Xiao,Yi Zuo,Yi Man,Yubao Li,Jidong Li
The regeneration of oral tissues is a challenging clinical problem because of the complex microbial and biological stress environments. Electrospun fibrous scaffolds have attracted significant interest as effective barrier membranes for guided bone regeneration (GBR); however, no mature strategy yet exists for the surface modification of fibers to provide versatility to satisfy clinical requirements. This study demonstrated a practical biosafety strategy: the combined use of plant polyphenols and LL-37 peptides to modify the fiber surface to endow the fibrous scaffold with antimicrobial activity, immunoregulation, and vascularized bone regeneration. We confirmed that the LL-37 peptides interacted with tannic acid (TA) through noncovalent bonds through experiments and molecular docking simulation analysis. In vitro experiments showed that the TA coating imparted strong antibacterial properties to the fibrous scaffold, but it also caused cytotoxicity. The grafting of LL-37 peptide promoted the spreading, migration, and osteogenic differentiation of mesenchymal stem cells and was also conducive to the M2 polarization of RAW264.7 cells. In vivo experiments further verified that the LL-37 peptide-grafted fibrous scaffold significantly enhanced angiogenesis, anti-inflammatory effects, and type-H vascularized bone regeneration. Overall, the fibrous scaffold modified by the LL-37 peptide through TA grafting has significant potential for GBR applications.
研究领域:
生物材料
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组织工程
·
再生医学
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2022
·
IF 4.331
Yabing Jin,Yijin Wang,Yuhong Chen,Tianlei Han,Yiyi Chen,Chen Wang
Polyetherketoneketone (PEKK) is considered to be a potential substitute material for metal bone implants because of its advantageous biocompatibility, chemical stability, and mechanical properties, but clinical application has been severely restricted due to PEKK’s lack of antibacterial ability and biological activity. In this study, LL-37, a natural human antimicrobial peptide, was successfully modified on the PEKK surface with polydopamine as the intermediate layer and released continuously for more than 6 days. The results of the MTT assay, colony counts, and Live/Dead staining demonstrated that compared to unmodified PEKK, the LL-37-modified PEKK significantly inhibited the adhesion, vitality, and bacterial biofilm growth of Staphylococcus aureus and Escherichia coli in a concentration-dependent way. Furthermore, the LL-37-modified PEKK enhanced biocompatibility (cell adhesion and viability) and promoted osteogenic differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells. Our data suggested that LL-37-modified PEKK might be a promising material for use in orthopedic implants.
研究领域:
生物材料
·
生物医学工程
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 5
·2416
·
IF 4.6
Junchen Liu,Yuehang Wu,Wenrui Ma,Hongyan Zhang,Xianyao Meng,Huirong Zhang,Miaomiao Guo,Xiao Ling,Li Li
Panax notoginseng(Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However,Panax notoginsengflower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX–2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL–37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography–tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX–2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.Keywords:Panax notoginsengflower;UVB;inflammatory factor;antibacterial peptide LL-37;total saponin;LC/MS/MS
研究领域:
药理学
·
生物化学
·
药物化学
·
化妆品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2024
·
IF 3.9
Guang Wang,Pei Li,Si-Wei Su,Rui Xu,Zi-Ye Huang,Tong-Xin Yang,Jiong-Ming Li
Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. Methods: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. Results: QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α. Conclusion: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.
研究领域:
药理学
·
分子生物学
·
生物信息学
·
泌尿学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 8
·177
·
IF 3.1
Pingping Lv,Huirong Zhang,Meiling Tai,Biao Che,Dan Yu,Ying Zhang,Haodong Li,Xianyao Meng,Miaomiao Guo,Li Li
Background: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. Methods: In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO’s anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry. Results: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. Conclusions: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.
研究领域:
药理学
·
皮肤科
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-13
·
IF 3.8
Zhou Liuyi,Chen Lulu,Li Ting,Wang Lu,Lin Shiqi,Zhao Ye,Wu Sufan,Jin Tingting
Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.
研究领域:
皮肤科
·
炎症性疾病
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 17
·期 6
·8385-8390
·
IF 1.922
Ting Li,Qingwen Zeng,Xingming Chen,Guojiang Wang,Haiqing Zhang,Aihua Yu,Hairui Wang,Yang Hu
Acne rosacea is a type of chronic dermatosis with the characteristics of erubescence, angiotelectasis and pustule formation. However, current treatment methods are limited due to the side effects. Artesunate demonstrated a promising therapeutic efficacy with a high safety margin. HaCaT cells were treated with antibacterial peptide LL‑37 to simulate rosacea caused by Demodex folliculorum (D. folliculorum) infection. Cell Counting kit 8 and flow cytometry assays were performed to measure cellular proliferation, apoptosis, the stage of the cell cycle and reactive oxygen species generation in order to determine the level of cell damage. Then the damaged cells were treated with different concentrations of artesunate and doxycycline to determine the therapeutic effect of artesunate. Pro‑inflammatory cytokines tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6, IL‑8 and C‑C motif chemokine 2 (MCP‑1) were measured using an ELISA, while western blotting was used to detect the expression of Janus kinase 2 (JAK2) and signal transducer and transcription activator (STAT3). As a result, LL‑37 treated HaCaT cells decreased in cell viability, had an increased apoptotic rate and cell cycle arrest, indicating that cell damage caused by rosacea was simulated. In addition, upregulated concentrations of the pro‑inflammatory cytokines TNF‑α, IL‑6, IL‑8 and MCP‑1 were attenuated in the artesunate group in a dose‑dependent fashion, indicating the therapeutic effect of artesunate. Furthermore, higher concentrations of artesunate exhibited an improved effect compared with the doxycycline group. In addition, increased expression levels of JAK2 and STAT3 following treatment with LL‑37 suggested that rosacea caused by D. folliculorum infection may lead to inflammation through the JAK/STAT signaling pathway. In conclusion, the potential mechanism by which damage occurs in rosacea was revealed and a promising therapeutic method against rosacea was demonstrated.
研究领域:
皮肤科
·
药理学
·
细胞生物学
·
免疫学
✓ 已验证
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）