Popat Ketul C, Eltgroth Matthew, Latempa Thomas J, Grimes Craig A, Desai Tejal A
Department of Physiology, Division of Bioengineering, University of California, 1700-4th Street, Box 2520, San Francisco, CA 94143-2520, USA.
Biomaterials. 2007 Nov;28(32):4880-8. doi: 10.1016/j.biomaterials.2007.07.037. Epub 2007 Aug 13.
Bacterial infection is one of the most common problems after orthopedic implant surgery. If not prevented, bacterial infection can result in serious and life threatening conditions such as osteomyelitis. Thus, in order to reduce chances of such serious complication, patients are often subjected to antibiotic drug therapy for 6-8 weeks after initial surgery. The antibiotics are systemically delivered either intravenously, intramuscularly or topically. Systemic antibiotic delivery entails certain drawbacks such as systemic toxicity and limited bioavailability. Further, in order for the drug to be effective at the site of implantation, high doses are required, which can result in undesired side effects in patients. Thus, local antibiotic therapy is the preferred way of administering drugs. To that end, we have developed titania nanotubular arrays for local delivery of antibiotics off-implant at the site of implantation. These nanotubes were fabricated on bulk titanium using anodization techniques. The fabrication strategies allow us to precisely control the nanotube length and diameter, thus enabling us to load different amounts of drugs and control the release rates. In this work we have fabricated titania nanotubes with 80 nm diameter and 400 nm length. We have loaded these tubes with 200, 400 and 600 microg of gentamicin. The gentamicin release kinetics from these nanotubes and its effect on Staphylococcus epidermis adhesion were investigated. Further, a preosteoblastic cell line called MC3T3-E1 was cultured on gentamicin-loaded nanotubes to evaluate the effect of nanoarchitecture on cell functionality. Our results indicate that we can effectively fill the nanotubes with the drug and the drug eluting nanotubes significantly reduce bacterial adhesion on the surface. Also, there is enhanced osteoblast differentiation on nanotubes filled with gentamicin.
细菌感染是骨科植入手术后最常见的问题之一。如果不加以预防,细菌感染可能会导致严重的、危及生命的状况,如骨髓炎。因此,为了降低此类严重并发症的发生几率,患者在初次手术后通常要接受6至8周的抗生素药物治疗。抗生素通过静脉注射、肌肉注射或局部给药等方式进行全身给药。全身给药存在一定的缺点,如全身毒性和生物利用度有限。此外,为了使药物在植入部位有效,需要高剂量给药,这可能会给患者带来不良副作用。因此,局部抗生素治疗是给药的首选方式。为此,我们开发了二氧化钛纳米管阵列,用于在植入部位局部递送植入体外的抗生素。这些纳米管是使用阳极氧化技术在块状钛上制备的。制备策略使我们能够精确控制纳米管的长度和直径,从而使我们能够装载不同量的药物并控制释放速率。在这项工作中,我们制备了直径为80纳米、长度为400纳米的二氧化钛纳米管。我们在这些纳米管中装载了200、400和600微克的庆大霉素。研究了这些纳米管中庆大霉素的释放动力学及其对表皮葡萄球菌黏附的影响。此外,在装载庆大霉素的纳米管上培养一种称为MC3T3-E1的前成骨细胞系,以评估纳米结构对细胞功能的影响。我们的结果表明,我们可以有效地将药物填充到纳米管中,且药物洗脱纳米管能显著降低表面细菌的黏附。此外,装载庆大霉素的纳米管上的成骨细胞分化增强。