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HHC36
NANOTECHNOLOGY · 2023 · IF 3.5

Strong infiltrative HHC36 antimicrobial peptide/silver nanoparticles-loaded carboxymethyl chitosan/sodium alginate hydrogel for acne vulgaris therapy

Hongju Liu,Jiezhao Zhan,Ruibin Lin,Ying Yin,Li Ren

Acne is a common chronic skin inflammatory disease closely related to Cutibacterium acnes (C. acnes), which affects the life quality of patients worldwide, especially adolescents and young adults. However, the physical barrier of the skin makes drugs difficult to infiltrate effectively into infected site, causing acne hard to cure and easy to recur. Herein, we developed an antibacterial skin dressing with strong infiltration of antibacterial agents which can co-delivery small-molecular antimicrobial agents through stratum corneum deeply into dermis, achieving high antimicrobial efficacy. The antibacterial dressings were constructed with carboxymethyl chitosan/sodium alginate (CMCS/SA) hydrogel loading with HHC36 (an antimicrobial peptide) and silver nanoparticles (AgNPs) conjugates (Ag-H2/CMCS/SA hydrogel). The released Ag-H2 from Ag-H2/CMCS/SA hydrogel can early infiltrate into dermis, co-delivery HHC36 and AgNPs due to the infiltration and targeting of HHC36, presenting the superior antibacterial effect compared to HHC36 or AgNPs alone and killing 100% C. acnes and 100% Staphylococcus epidermidis (S. epidermidis) at a very low concentration of Ag-H2 (15 μg/mL Ag with 7.1 μg/mL HHC36). Meanwhile, Ag-H2/CMCS/SA hydrogel was biocompatible due to the natural polysaccharides carboxymethyl chitosan and sodium alginate. The HaCaT cells spread well in Ag-H2/CMCS/SA hydrogel extracts. These results indicate that the co-delivery small-molecular antimicrobial agents is a promising strategy and Ag-H2/CMCS/SA hydrogel has a great potential in the therapy of acne.

研究领域: 药学 · 材料科学 · 生物医学工程 · 皮肤科
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

A promoted copper-catalysed Azide-alkyne cycloaddition (CuAAC) for broad spectrum peptide-engineered implants

Guansong Hu,Junjian Chen,Yan Fan,Haiyan Zhou,Kunzhong Guo,Zhou Fang,Liangxu Xie,Lin Wang,Yingjun Wang

As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azide-alkyne cycloaddition (CuAAC) urgently requires improvement. Herein, we constructed a facile CuAAC system with catalytic CuSO 4 /sodium borohydride (CuAAC-Bor). As Cu nanoclusters (CuNCs) formed in situ , they showed stronger efficiency in immobilizing 41 types of peptides on Ti implants than traditional CuAAC with CuSO 4 /sodium ascorbate. Then, we mechanically revealed the significance of peptide size on CuAAC efficiency by all-atom molecular dynamics simulation and machine learning, and found that larger peptides preferred to adhere to Ti and CuNCs to increase their reaction opportunity. With CuAAC-Bor, HHC36-engineered implants strongly inhibited 5 types of clinical bacteria in vitro and prevented infection in vivo , and RGD-, DGEA-, QK- or YGFGG-engineered implants had high biocompatibilities with HUVECs / hBMSCs in vitro . Moreover, we demonstrated that QK-engineered implants prepared with CuAAC-Bor promoted the osteogenic differentiation of hBMSCs via the PI3K/Akt signalling pathway and triggered angiogenesis and osteogenesis in vivo . Our study shows that this facile and highly efficient CuAAC-Bor system holds high promise for the preparation of novel biomaterial surfaces.

研究领域: 生物材料 · 生物医学工程 · 分子生物学 · 材料科学
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BIOMATERIALS · 2020 · IF 10.317

Fusion peptide engineered “statically-versatile” titanium implant simultaneously enhancing anti-infection, vascularization and osseointegration

Junjian Chen,Guansong Hu,Tianjie Li,Yunhua Chen,Meng Gao,Qingtao Li,Lijing Hao,Yongguang Jia,Lin Wang,Yingjun Wang

Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration . Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially “statically-versatile” ones with nonessential external stimulations for facilitating applications. Herein, we develop a “statically-versatile” titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria ( S. aureus , E. coli , P. aeruginosa and methicillin-resistant S. aureus ), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation , up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs . In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus , and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing “statically-versatile” orthopedic implants .

CAS / MDL: 7787-70-4
研究领域: 骨科 · 材料科学 · 生物材料 · 组织工程 · 生物医学工程
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