Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristic

Comparison of mechanical rigidity between plate augmentation leaving the nail in situ and interlocking nail using cadaveric fracture model of the femur

Thirteen matched pairs of cadaveric femurs were placed into two groups. In each group, a transverse fracture was created at a point 70% distal between the lesser trochanter and the adductor tubercle. One femur out of each matched pair was then stabilised with an interlocking intramedullary nail (nail only group) and the other femur was stabilised with plate augmentation after interlocking intramedullary nailing (plate augmentation group). The bending load to promote 5-mm displacement showed statistically significant differences between the plate augmentation group (mean 843.36 ± 409.13 N) and the nail only group (mean 315.02 ± 219.80 N) (p = 0.001). Torsional torque at the angle of 15 degrees showed statistically significant differences between the two groups; a mean of 2.09 ± 0.53 N·m for the plate augmentation group and a mean of 0.63 ± 0.46 N·m for the nail only group (p = 0.0001). We found a 2.6-fold increase in bending stiffness and a 3.3-fold increase in torsional stiffness in plate augmentation leaving a nail in situ compared to interlocking nailing only in the distal third fracture of femur