Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biomaterials. 2010 Aug;31(23):6019-30. doi: 10.1016/j.biomaterials.2010.04.011. Epub 2010 May 21.
While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to address an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 microg/cm(2). The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis.
虽然骨科植入物的感染率较低，但所需的治疗方法（包括六周的抗生素治疗和另外两次手术）可能危及生命且费用高昂，因此需要开发一种一次性再植入手术。采用层层沉积法制备了载有庆大霉素的聚电解质多层膜，用作装置涂层，以在直接植入物更换手术中解决现有的骨感染问题。在最初的三天内，这些薄膜体外释放了约 70%的载药量，随后继续释放药物超过四周，总平均释放量超过 550μg/cm(2)。这些涂层被证明对金黄色葡萄球菌具有杀菌作用，并且降解产物通常对 MC3T3-E1 鼠前成骨细胞没有毒性。在金黄色葡萄球菌骨感染模型中，将涂有薄膜的钛植入物与未涂覆的植入物进行了比较。在直接交换手术后，抗菌涂层装置在第 4 天（p<0.004）和第 7 天（p<0.03）时，其骨匀浆的感染程度明显低于未涂层装置。这项研究表明，自组装的超薄薄膜涂层能够有效地治疗体内实验性骨感染，并为开发用于优化、协同治疗疼痛、感染和骨髓炎的多治疗性薄膜奠定了基础。
