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Combining local antibiotic delivery with heparinized nanohydroxyapatite/collagen bone substitute: A novel strategy for osteomyelitis treatment
Biomaterials Advances ( IF 5.5 ) Pub Date : 2020-08-07 , DOI: 10.1016/j.msec.2020.111329
Tatiana Padrão , Catarina C. Coelho , Paulo Costa , Nuno Alegrete , Fernando J. Monteiro , Susana R. Sousa

Osteomyelitis is a major challenge in bone surgery and conventional treatment is frequently ineffective to control the infection, with an alternative approach being required. In the present work, a heparinized nanohydroxyapatite/collagen biocomposite was produced in granular form, and loaded with vancomycin, to work as a local drug delivery system for osteomyelitis and as a bone substitute. This strategy involves the local delivery of high concentrations of vancomycin, to eradicate the infection. Additionally, these granules work as a scaffold with regenerative properties, to induce bone regeneration after antibiotic release. The heparinized nanohydroxyapatite/collagen granular bone substitute was produced using two different sintering temperatures to study their effect on granules properties and on vancomycin release profile. Morphological, topographic, chemical and mechanical characterization were carried out for granules sintered at both temperatures and some relevant differences were found. The mechanical strength was increased by several orders of magnitude with increasing sintering temperature, being able to maintain their porous macrostructure and withstand important processes for their commercialization such as packaging, shipping and surgical manipulation. The nanohydroxyapatite/collagen granules were able to release high concentrations of vancomycin, always above MIC, for 19 days. The released antibiotic was able to eradicate both planktonic and sessile methicillin-resistant Staphylococcus aureus. The cytotoxicity was assessed according to ISO 10993-5:2009 and the granules sintered at higher temperature showed no cytotoxic effect. Considering these results nanohydroxyapatite/collagen biocomposite loaded with vancomycin is a promising solution for osteomyelitis treatment.



中文翻译:

结合局部抗生素与肝素化的纳米羟基磷灰石/胶原蛋白骨替代品:治疗骨髓炎的新策略

骨髓炎是骨外科手术中的主要挑战,常规治疗通常无法有效控制感染,因此需要替代方法。在目前的工作中,肝素化的纳米羟基磷灰石/胶原蛋白生物复合物以颗粒形式生产,并装载了万古霉素,作为骨髓炎的局部药物递送系统和骨替代品。该策略涉及局部递送高浓度万古霉素以根除感染。另外,这些颗粒用作具有再生特性的支架,以在抗生素释放后诱导骨再生。使用两种不同的烧结温度生产肝素化的纳米羟基磷灰石/胶原粒状骨替代品,以研究其对颗粒性质和万古霉素释放曲线的影响。形态 对在两个温度下烧结的颗粒进行了形貌,化学和机械表征,并发现了一些相关差异。随着烧结温度的提高,机械强度提高了几个数量级,能够保持其多孔的宏观结构并经受其商业化的重要过程,例如包装,运输和外科手术。纳米羟基磷灰石/胶原颗粒能够释放高浓度的万古霉素(通常高于MIC)达19天。释放的抗生素能够根除对浮游和顽固的耐甲氧西林 随着烧结温度的提高,机械强度提高了几个数量级,能够保持其多孔的宏观结构并经受其商业化的重要过程,例如包装,运输和外科手术。纳米羟基磷灰石/胶原颗粒能够释放高浓度的万古霉素(通常高于MIC)达19天。释放的抗生素能够根除对浮游和顽固的耐甲氧西林 随着烧结温度的提高,机械强度提高了几个数量级,能够保持其多孔的宏观结构并经受其商业化的重要过程,例如包装,运输和外科手术。纳米羟基磷灰石/胶原颗粒能够释放高浓度的万古霉素(通常高于MIC)达19天。释放的抗生素能够根除对浮游和顽固的耐甲氧西林金黄色葡萄球菌。根据ISO 10993-5:2009评估细胞毒性,并且在较高温度下烧结的颗粒没有显示出细胞毒性作用。考虑到这些结果,负载万古霉素的纳米羟基磷灰石/胶原生物复合材料是治疗骨髓炎的有前途的解决方案。

更新日期:2020-09-12
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