Study of the release kinetics of dalbavancin from bone allografts

IF 4.5 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Roger Erivan, Nicolas Bourzat, Mouloud Yessaad, Guillaume Villatte, Stéphane descamps, Stéphane Boisgard, Philip Chennell
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Abstract

Bone infections are common and difficult to treat, and secondary bone defects, which are often observed, may require a bone allograft. In this case, the surgeon will add antibiotics (usually vancomycin) in direct contact with the bone graft during the procedure, in order to allow in-situ release after implantation in the operating site. Dalbavancin is a novel antibiotic indicated for treating acute bacterial infections resistant to vancomycin. Its modified chemical structure grants it an increased half-life that could modify its release kinetics from the bone allograft. The aim of this study was to determine the release kinetics of dalbavancin from bone grafts after they were immersed in a dalbavancin solution. The study was conducted using a Design of Experiments (DoE) protocol. Decellularized and delipidated allograft bone cubes were preliminarily characterized and put into contact with dalbavancin solutions. The parameters that were studied where the allograft mass, initial dalbavancin concentration and contact time. The samples were then transferred into the release media, which was sampled over time and dalbavancin was quantified using a high pressure liquid chromatography with diode array detector method that was developed for the occasion. Our results showed that on average, dalbavancin was fully released after 5 min for the lower mass bone grafts, but after 60 min for the high mass and high concentration conditions. Contact time had no impact, thus indicating a fast loading process of dalbavancin into the allograft. Although our study revealed the possible benefits of using dalbavancin in bone grafting, an in-vivo study is required to confirm our hypotheses.

Graphical Abstract

dalbavancin在同种异体骨移植中的释放动力学研究
骨感染是常见的,难以治疗,继发性骨缺损,这往往观察到,可能需要骨移植异体。在这种情况下,外科医生将在手术过程中添加与骨移植物直接接触的抗生素(通常是万古霉素),以便在植入手术部位后允许原位释放。Dalbavancin是一种新型抗生素,用于治疗万古霉素耐药的急性细菌感染。其改良的化学结构使其半衰期延长,从而可以改变其从同种异体骨移植中释放的动力学。本研究的目的是确定骨移植物浸泡在达尔巴万素溶液后达尔巴万素的释放动力学。本研究采用实验设计(DoE)方案进行。初步表征脱细胞和腐烂的同种异体骨块,并将其与达尔巴万辛溶液接触。研究了同种异体移植物的质量、初始浓度和接触时间。然后将样品转移到释放介质中,随时间采样,并使用专为该场合开发的高压液相色谱二极管阵列检测器方法定量测定达尔巴万辛。我们的研究结果显示,对于低质量骨移植,达尔巴万辛平均在5分钟后完全释放,而对于高质量和高浓度骨移植,达尔巴万辛平均在60分钟后完全释放。接触时间不受影响,表明达巴万辛在同种异体移植物中的加载过程很快。虽然我们的研究揭示了在骨移植中使用达尔巴伐辛的可能益处,但需要一项体内研究来证实我们的假设。图形抽象
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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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