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具有强杀菌、抑菌和抗生物膜活性的非细胞毒性锌掺杂纳米羟基磷灰石基骨支架。

Noncytotoxic zinc-doped nanohydroxyapatite-based bone scaffolds with strong bactericidal, bacteriostatic, and antibiofilm activity.

机构信息

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

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

出版信息

Biomater Adv. 2022 Aug;139:213011. doi: 10.1016/j.bioadv.2022.213011. Epub 2022 Jul 4.

DOI:10.1016/j.bioadv.2022.213011
PMID:35882155
Abstract

Development of bone scaffolds that are nontoxic to eukaryotic cells, while revealing bactericidal activity still remains a huge challenge for the scientific community. It should be noted that only bacteriostatic (the ability of the biomaterial to inhibit the growth of bacteria) and bactericidal (the ability to kill >99.9 % bacteria) activities have clinical importance. Unfortunately, many material scientists are confused with the microbiological definition of antibacterial action and consider biomaterials causing reduction in colony-forming units (CFUs) by 50-80 % as promising antibacterial implants. The aim of this study was to synthesize three variants of Zn-doped hydroxyapatite (HA) nanopowder, which were characterized by different content of Zn and served as a powder phase for the production of novel macroporous chitosan/agarose/nanoHA biomaterials with high antibacterial activity. Within this study, it was proven that the scaffold with a low zinc content (doping level 0.03 mol for 1 mol of HA; 0.2 wt%) revealed the gradual and slow release of the Zn ions, preventing against accumulation of high and toxic concentration of therapeutic agents and providing prolonged antibacterial activity. Moreover, developed biomaterial was nontoxic to human osteoblasts and showed anti-biofilm properties, bactericidal activity (> 99.9 % of bacteria killed) against Staphylococcus epidermidis and Escherichia coli, significant antibacterial activity against Staphylococcus aureus (98.5 % of bacteria killed), and also bacteriostatic activity against Pseudomonas aeruginosa. Thus, the developed Zn-doped HA-based bone scaffold has excellent antibacterial properties without toxicity against eukaryotic cells, being a promising biomaterial for biomedical applications to repair bone defects and prevent post-surgery infections.

摘要

开发对真核细胞无毒、同时具有杀菌活性的骨支架仍然是科学界面临的巨大挑战。值得注意的是,只有抑菌(生物材料抑制细菌生长的能力)和杀菌(杀死>99.9%细菌的能力)活性具有临床意义。不幸的是,许多材料科学家对抗菌作用的微生物学定义感到困惑,并认为生物材料使菌落形成单位(CFU)减少 50-80%就有希望成为具有抗菌作用的植入物。本研究的目的是合成三种不同锌掺杂浓度的羟基磷灰石(HA)纳米粉末,其特征为不同的锌含量,并作为粉末相用于制备具有高抗菌活性的新型大孔壳聚糖/琼脂糖/纳米 HA 生物材料。在本研究中,证明了锌含量低(掺杂水平为 1 摩尔 HA 中掺杂 0.03 摩尔锌;0.2wt%)的支架具有逐渐缓慢释放锌离子的特性,防止治疗剂的高浓度和毒性积累,从而提供持久的抗菌活性。此外,开发的生物材料对人成骨细胞无毒,具有抗生物膜特性,对表皮葡萄球菌和大肠杆菌具有杀菌活性(>99.9%的细菌被杀灭),对金黄色葡萄球菌具有显著的抗菌活性(98.5%的细菌被杀灭),对铜绿假单胞菌也具有抑菌活性。因此,开发的基于锌掺杂 HA 的骨支架具有优异的抗菌性能,对真核细胞无毒,是一种有前途的生物材料,可用于修复骨缺损和预防术后感染的生物医学应用。

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