Department of Engineering Sciences, Science for Life Laboratory, Uppsala University, Box 534, 751 21 Uppsala, Sweden.
Biomaterials, Biomechanics and Tissue Engineering Group, Dpt. Materials Science and Metallurgy, Universitat Politècnica de Catalunya (UPC), Av. Eduard Maristany 10-14, 08019 Barcelona, Spain; Research Centre in Multiscale Science and Engineering, UPC, Barcelona, Spain.
Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:84-95. doi: 10.1016/j.msec.2018.11.064. Epub 2018 Nov 28.
The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 μm vs. macroporosity, i.e. >5 μm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.
本研究旨在评估不同的体内抗菌疗法对新西兰兔股骨头骨髓炎的治疗效果。共评估了 5 种磷酸盐类水泥：磷酸钙水泥（CPC）和磷酸钙泡沫（CPF），均为原始形式以及负载盐酸多西环素的形式，还有一种具有内在抗菌作用的镁磷酸盐水泥（MPC；未负载抗生素）。将这些水泥植入先前感染金黄色葡萄球菌的骨中，以区分抗生素给药方式（全身 vs 局部）、孔隙率（微孔，即 <5 μm 与大孔，即 >5 μm）和抗菌机制类型（抗生素释放与内在抗菌活性）对感染动物健康状况改善的影响。开发了一种新方法，采用更全面的综合评分，综合了骨感染的 5 个参数、骨结构完整性的 4 个参数和骨再生的 4 个参数。该方法用于评估感染动物在骨髓炎治疗前后的健康状况。结果表明，综合评分能够辨别出个体评估无法识别的治疗方法之间的统计学显著差异。尽管没有一种治疗方法能完全消除感染，但观察到大孔材料（CPF 和 CPFd，后者负载盐酸多西环素）和具有内在抗菌作用的 MPC 能更好地控制骨髓炎。本研究为理解体内不同抗菌疗法的效果提供了新的见解，并开发了一种有前景的综合方法来评估动物的健康状况。我们期望这种方法的实施可以改善选择适当抗菌疗法的标准。
