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载有庆大霉素和掺锌纳米羟基磷灰石的生物相容性凝乳多糖基生物材料,可用作治疗感染性伤口和预防手术部位感染的有前途的敷料材料。

Biocompatible curdlan-based biomaterials loaded with gentamicin and Zn-doped nano-hydroxyapatite as promising dressing materials for the treatment of infected wounds and prevention of surgical site infections.

机构信息

Independent Unit of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland.

Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland.

出版信息

Biomater Adv. 2022 Aug;139:213006. doi: 10.1016/j.bioadv.2022.213006. Epub 2022 Jun 28.

Abstract

A topical application of antibiotic-loaded wound dressings is recommended only for chronically infected wounds with poor vascularization. Thus, more often dressing materials loaded with antibacterial metal ions are produced. In turn, gentamicin sponges are commonly used to prevent surgical site infections. The aim of this study was to produce curdlan-based biomaterials enriched with gentamicin and zinc (Zn)-doped nano-hydroxyapatite to prevent wound and surgical site infections. Developed biomaterials were subjected to basic microstructural characterization, cytotoxicity test against human skin fibroblasts (BJ cell line), and comprehensive microbiological experiments using Staphylococcus aureus and Pseudomonas aeruginosa strains. To evaluate the in vivo healing capacity of the developed biomaterials, severely infected chronic wound in a veterinary patient was treated with the use of gentamicin-loaded dressing. Fabricated biomaterials were characterized by a highly porous microstructure with high plasma absorption capacity (approx. 7 mL/g for Zn-loaded biomaterial and 13 mL/g for gentamicin-enriched dressing) and optimal water vapor transmission rate (approx. 1700 g/m/day). Due to the presence of bioceramics, material containing Zn showed slightly higher compressive strength (0.37 MPa) and Young's modulus (3.33 MPa) values compared to gentamicin-loaded biomaterial (0.12 MPa and 1.29 MPa, respectively). Gentamicin-enriched biomaterial showed burst release of the drug within the first 5 h, while, the zinc-loaded biomaterial exhibited a constant gradual release of the zinc ions. Conducted assays showed that developed biomaterials were non-toxic against human skin fibroblasts (cell viability in the range of 71-95 %) and revealed strong bactericidal activity (99.9 % reduction in the number of viable bacterial CFUs in direct contact test) against S. aureus. In the case of P. aeruginosa, only gentamicin-loaded biomaterial exhibited bactericidal effect. Additionally, biomaterials had the ability to uptake, lock in, and kill bacteria within their gel structure, enabling the cleansing of the wound bed at every dressing change. Finally, the treatment of severely infected wound in veterinary patient confirmed the effectiveness of gentamicin-loaded biomaterial. Biomaterial enriched with gentamicin possesses great potential to be used as a dressing material or sponge for the treatment of chronically infected wounds and surgical site infections. In turn, the zinc-loaded biomaterial may be used as a wound dressing to reduce and prevent microbial contamination.

摘要

局部应用载抗生素的创伤敷料仅推荐用于血供差的慢性感染性创面。因此,更多的是生产载抗菌金属离子的敷料材料。相反,庆大霉素海绵常用于预防手术部位感染。本研究的目的是制备富含庆大霉素和锌(Zn)掺杂纳米羟基磷灰石的卡拉胶基生物材料,以预防伤口和手术部位感染。对所开发的生物材料进行了基本微观结构表征、对人皮肤成纤维细胞(BJ 细胞系)的细胞毒性测试以及使用金黄色葡萄球菌和铜绿假单胞菌的综合微生物实验。为了评估所开发生物材料的体内愈合能力,使用载庆大霉素的敷料治疗兽医患者严重感染的慢性伤口。所制备的生物材料具有高度多孔的微观结构,具有高的等离子体吸收能力(载锌生物材料约为 7 mL/g,庆大霉素富集敷料约为 13 mL/g)和最佳的水蒸气透过率(约 1700 g/m/day)。由于存在生物陶瓷,含锌的材料显示出略高的抗压强度(0.37 MPa)和杨氏模量(3.33 MPa)值,而载庆大霉素的生物材料分别为 0.12 MPa 和 1.29 MPa。载庆大霉素的生物材料在最初的 5 小时内表现出药物的爆发释放,而载锌的生物材料则表现出锌离子的持续缓慢释放。进行的测定表明,所开发的生物材料对人皮肤成纤维细胞无毒性(细胞活力在 71-95%范围内),并对金黄色葡萄球菌表现出很强的杀菌活性(直接接触试验中存活细菌 CFU 数量减少 99.9%)。对于铜绿假单胞菌,只有载庆大霉素的生物材料表现出杀菌作用。此外,生物材料具有在其凝胶结构内吸收、锁定和杀死细菌的能力,从而能够在每次更换敷料时清洁伤口床。最后,兽医患者严重感染伤口的治疗证实了载庆大霉素生物材料的有效性。载庆大霉素的生物材料具有作为慢性感染性伤口和手术部位感染治疗用敷料或海绵的巨大潜力。相反,载锌的生物材料可用作伤口敷料,以减少和预防微生物污染。

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