A bio-artificial poly([d,l]-lactide-co-glycolide) drug-eluting nanofibrous periosteum for segmental long bone open fractures with significant periosteal stripping injuries

Abstract

Biodegradable poly([d,l]-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with two drug-to-polymer weight ratios, namely 1:3 and 1:6, which comprised PLGA 180 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, and PLGA 360 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, respectively, was produced as an artificial periosteum in the treatment of segmental femoral fractures. The nanofibrous membrane’s drug release behavior was assessed in vitro using high-performance liquid chromatography and the disk-diffusion method. A femoral segmental fracture model with intramedullary Kirschner-wire fixation was established for the in vivo rabbit activity study. Twenty-four rabbits were divided into two groups. Twelve rabbits in group A underwent femoral fracture fixation only, and 12 rabbits in group B underwent femoral fracture fixation and were administered the drug-loaded nanofibers. Radiographs obtained at 2, 6, and 12 weeks postoperatively were used to assess the bone unions. The total activity counts in animal behavior cages were also examined to evaluate the clinical performance of the rabbits. After the animals were euthanized, both femoral shafts were harvested and assessed for their torque strengths and toughness. The daily in vitro release curve for lidocaine showed that the nanofibers eluted effective levels of lidocaine for longer than 3 weeks. The bioactivity studies of vancomycin and ceftazidime showed that both antibiotics had effective and sustained bactericidal capacities for over 30 days. The findings from the in vivo animal activity study suggested that the rabbits with the artificial drug-eluting periosteum exhibited statistically increased levels of activity and better clinical performance outcomes compared with the rabbits without the artificial periosteum. In conclusion, this artificial drug-eluting periosteum may eventually be used for the treatment of open fractures.

Keywords:

• artificial periosteum
• biodegradable poly([d,l]-lactide-co-glycolide) drug-eluting nanofibers
• polycaprolactone stents
• segmental long bone open fractures

Acknowledgments

The authors thank Dr Jau-Wen Huang and the staff of the Ci-Wen Clinic for their assistance with preparing the images and radiographs for this study. The authors would also like to thank the Ministry of Science and Technology, Taiwan (contract no MOST 104-2221-E-182-048-MY3) and Chang Gung Memorial Hospital (contract no CMRPD3D0151) for supporting this research financially.

Disclosure

The authors report no conflicts of interest in this work.