International Journal of Nanomedicine (Feb 2020)
A Three-Dimensional Printed Polycaprolactone Scaffold Combined with Co-Axially Electrospun Vancomycin/Ceftazidime/Bone Morphological Protein-2 Sheath-Core Nanofibers for the Repair of Segmental Bone Defects During the Masquelet Procedure
Abstract
Yi-Hsun Yu,1,2 Demei Lee,2 Yung-Heng Hsu,1,2 Ying-Chao Chou,1,2 Steve WN Ueng,1 Che-Kang Chen,2 Shih-Jung Liu1,2 1Department of Orthopedic Surgery, Musculoskeletal Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Road, Guishan District, Taoyuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email [email protected]: Masquelet proposed a new solution for the healing of segmental bone defects, thus minimizing the disadvantages associated with traditional bone grafting. However, a major factor leading to the failure of this technique pertains to be the residual infection. Accordingly, we developed an antibiotic- and osteo-inductive agent-loaded composite scaffold to solve this problem.Methods: A mesh-like polycaprolactone scaffold was prepared using a lab-exploited solution-type three-dimensional printer, and hybrid sheath-core structured poly(lactic-co-glycolic-acid) nanofibers were fabricated using co-axial electrospinning technology. Vancomycin, ceftazidime, and bone morphological protein (BMP)-2 were employed. The in vitro and in vivo (rabbit fracture model) release patterns of applied agents from the composite scaffold were investigated.Results: The results revealed that the drug-eluting composite scaffold enabled the sustainable release of the medications for at least 30 days in vitro. Animal tests demonstrated that a high concentration of medications was maintained. Abundant growth factors were induced within the bioactive membrane stimulated by the applied scaffold. Finally, satisfactory bone healing potential was observed on radiological examination and biomechanical evaluation.Discussion: The developed composite scaffold may facilitate bone healing by inducing bioactive membrane formation and yielding high concentrations of antibiotics and BMP-2 during the Masquelet procedure.Keywords: Masquelet procedure, composite scaffold, three-dimensional printing, co-axial electrospinning