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基于丝素的抗菌聚合物作为一种新平台,设计无药物的材料以阻止微生物感染。

Silk-Based Antimicrobial Polymers as a New Platform to Design Drug-Free Materials to Impede Microbial Infections.

机构信息

3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal.

ICVS/3B's - PT Government Associate Laboratory, 4805 Braga/Guimarães, Portugal.

出版信息

Macromol Biosci. 2018 Dec;18(12):e1800262. doi: 10.1002/mabi.201800262. Epub 2018 Nov 8.

DOI:10.1002/mabi.201800262
PMID:30408337
Abstract

Surgical site infections (SSI) represent a serious health problem that occur after invasive surgery, thus new antimicrobial biomaterials able to prevent SSI are needed. Silks are natural biopolymers with excellent biocompatibility, low immunogenicity and controllable biodegradability. Spider silk-based materials can be bioengineered and functionalized with specific peptides, such as antimicrobial peptides, creating innovative polymers. Herein, we explored new drug-free multifunctional silk films with antimicrobial properties, specifically tailored to hamper microbial infections. Different spider silk domains derived from the dragline sequence of the spider Nephila clavipes (6mer and 15mer, 27 and 41 kDa proteins, respectively) were fused with the two antimicrobial peptides, Hepcidin (Hep) and Human Neutrophil peptide 1 (HNP1). The self-assembly features of the spider silk domains (β-sheets) were maintained after functionalization. The bioengineered 6mer-HNP1 protein demonstrated inhibitory effects against microbial pathogens. Silk-based films with 6mer-HNP1 and different contents of silk fibroin (SF) significantly reduced bacterial adhesion and biofilm formation, whereas higher bacterial counts were found on the films prepared with 6mer or SF alone. The silk-based films showed no cytotoxic effects on human foreskin fibroblasts. The positive cellular response, together with structural and antimicrobial properties, highlight the potential of these multifunctional silk-based films as new materials for preventing SSI.

摘要

手术部位感染(SSI)是一种严重的健康问题,发生在侵袭性手术后,因此需要新的能够预防 SSI 的抗菌生物材料。丝是具有优异生物相容性、低免疫原性和可控制的生物降解性的天然生物聚合物。蜘蛛丝基材料可以通过生物工程和功能化特定的肽,如抗菌肽,来创造创新的聚合物。在此,我们探索了具有抗菌特性的新型无药物多功能丝膜,专门用于抑制微生物感染。从蜘蛛 Nephila clavipes 的拖丝序列中衍生出不同的丝域(6mer 和 15mer,分别为 27 和 41 kDa 的蛋白质)与两种抗菌肽 Hepcidin(Hep)和 Human Neutrophil peptide 1(HNP1)融合。丝域(β-折叠)的自组装特性在功能化后得以保持。经生物工程改造的 6mer-HNP1 蛋白对微生物病原体表现出抑制作用。含有 6mer-HNP1 和不同含量丝素蛋白(SF)的丝基膜显著减少了细菌黏附和生物膜形成,而单独使用 6mer 或 SF 制备的膜上细菌计数更高。丝基膜对人包皮成纤维细胞没有细胞毒性作用。积极的细胞反应,加上结构和抗菌性能,突出了这些多功能丝基膜作为预防 SSI 的新材料的潜力。

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