Ter Boo Gert-Jan A, Arens Daniel, Metsemakers Willem-Jan, Zeiter Stephan, Richards R Geoff, Grijpma Dirk W, Eglin David, Moriarty T Fintan
AO Research Institute Davos, Davos, Switzerland; MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
AO Research Institute Davos, Davos, Switzerland.
Acta Biomater. 2016 Oct 1;43:185-194. doi: 10.1016/j.actbio.2016.07.029. Epub 2016 Jul 17.
Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis.
Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel thermo-responsive hyaluronan based hydrogel with control over gelation temperature is reported. The efficacy of this gentamicin loaded hyaluronan derivative is demonstrated in an in vivo fracture model in the presence of fracture fixation hardware. The bacterial burden is cleared in all of the inoculated rabbits in the presence of the ALB. Thus, the proposed injectable thermo-responsive hyaluronan presents an effective ALB for the prevention of infection.
尽管使用了全身性抗生素预防措施，但采用骨合成植入物对外开放性骨折进行手术固定仍伴有较高的感染率。负载抗生素的生物材料（ALB）在各个医学专科的植入手术中越来越多地被使用，以将高浓度抗生素输送到手术部位并降低植入相关感染的风险。在空间分布方面限制较少或没有限制且可应用于整个复杂伤口的ALB，可能会为开放性骨折护理提供更好的抗感染保护。通过透明质酸的四丁基铵（TBA）盐与胺端基聚（N-异丙基丙烯酰胺）（pN）之间的直接酰胺化反应制备了一种热响应性透明质酸衍生物（透明质酸-聚（N-异丙基丙烯酰胺）（HApN））。对该凝胶的接枝度和凝胶化性质进行了表征，并在其中负载了庆大霉素。在体外测试了这种负载庆大霉素的HApN组合物的流变学和释放特性，并在金黄色葡萄球菌污染的骨合成兔模型中测试了其预防感染的功效。定量细菌学表明，负载庆大霉素的HApN组合物能够防止植入部位的细菌定植。对肱骨样本的组织病理学评估支持了这一发现，在染色切片中未发现细菌。总之，这种负载庆大霉素的HApN水凝胶有效地预防了复杂伤口中的感染，模拟了用钢板骨合成治疗的污染骨折。
创伤后的骨折固定与高感染率相关。负载抗生素的生物材料（ALB）可提供高局部浓度且无全身副作用。然而，由于预定形状，目前可用的ALB对开放性骨折中受污染组织的可达性有限。因此，报道了一种新型的基于热响应性透明质酸的水凝胶，其凝胶化温度可控。在存在骨折固定硬件的体内骨折模型中证明了这种负载庆大霉素的透明质酸衍生物的功效。在存在ALB的情况下，所有接种兔子的细菌负荷均被清除。因此，所提出的可注射热响应性透明质酸是一种预防感染的有效ALB。
