Seidenstuecker Michael, Ruehe Juergen, Suedkamp Norbert P, Serr Annerose, Wittmer Annette, Bohner Marc, Bernstein Anke, Mayr Hermann O
Center of Surgery, Department of Orthopedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
University of Freiburg, IMTEK, Department of Microsystems Engineering, Chemistry and Physics of Interfaces, Germany.
Acta Biomater. 2017 Mar 15;51:433-446. doi: 10.1016/j.actbio.2017.01.045. Epub 2017 Jan 16.
The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28days.
Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10mL double-distilled water for 4weeks at 37°C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA.
The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2±1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14days. The burst release here was 61.9±4.3%. The native alginate's burst release was 54.1±7.8%; that of the sterile alginate 40.5±6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0μg/mL against Staphylococcus aureus.
Drug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the "granule in hydrogel" composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work.
本研究旨在制备一种新型复合材料，该材料由填充藻酸盐和万古霉素（VAN）的微孔β - 磷酸三钙组成，以使抗生素的释放行为延长至28天。
使用该团队开发的流动腔，在定向流动中将多孔陶瓷填充不同组成且含有50mg/mL抗生素的藻酸盐。在用钙离子交联藻酸盐后，于37°C在10mL双蒸水中孵育4周。在规定时间（1、2、3、6、9、14、20和28天），完全更换液体，并通过毛细管区带电泳和微量滴定试验进行分析。出于统计目的，计算均值和标准差，并通过方差分析进行分析。
在整个期间，万古霉素从藻酸盐中的释放是通过外部钙源进行的，其浓度高于最低抑菌浓度（MIC）。测得的突释为35.2±1.5%。仅在14天内观察到了从具有内部钙源的藻酸盐中释放万古霉素。此处的突释为61.9±4.3%。天然藻酸盐的突释为54.1±7.8%；无菌藻酸盐的突释为40.5±6.4%。微量滴定实验显示在整个研究期间万古霉素均有效。在释放实验中针对金黄色葡萄球菌测定的MIC值在0.5 - 2.0μg/mL范围内。
基于β - 磷酸三钙和水凝胶的药物释放系统在文献中有充分记载。然而，在所有描述的系统中，陶瓷作为颗粒或粉末被插入水凝胶中。在我们的工作中，我们做了相反的操作，即将作为抗生素储存库的水凝胶置于多孔可生物降解陶瓷中。最终，该系统应应用于骨感染的治疗。与“水凝胶中的颗粒”复合材料相反，它具有机械稳定性的优势。因此，它可以在愈合过程中承担骨骼的功能。为了更快地将我们的科研成果转化为临床应用，本工作仅使用了美国食品药品监督管理局（FDA）批准的材料。
