Zoledronate loaded polylactic acid/polycaprolactone/hydroxyapatite scaffold accelerates regeneration and led to enhance structural performance and functional ability of the radial bone defect in rat

BACKGROUND: One of the most common concerns in the regeneration of massive bone defects necessitating surgery and bone grafts is the application of tissue engineering using drug delivery. Zoledronate is a well-known effective drug for the healing bone fractures in osteoporotic patients. AIMS: An attempt was made to design a more efficient bone scaffold with polycaprolactone, polylactic acid, and hydroxyapatite. METHODS: The scaffold was fabricated by freeze-drying and indirect 3D printing approaches. X-ray diffraction, Fourier transform infrared spectroscopy, rheometry, scanning electron microscopy, and neutral red tests were performed to characterize the scaffold. qRT-PCR was also done to define the osteoinductivity and angiogenic induction capacity of this scaffold. Forty rats were selected and randomly divided into four groups: the control group, which received no treatment, the autograft group, scaffold group, and Zol-loaded scaffold group (n=10 in each group). The injured area was studied by radiology, biomechanical analysis, histopathology, histomorphometry, immunohistochemistry, and CT scan analyses. RESULTS: The qRT-PCR results demonstrated significantly higher expression levels of OPN, OCN, and CD31 markers in the scaffold group when compared to the control group (P<0.05). Histopathologically, the newly formed bone tissue was significantly detected in the Zol-loaded scaffold and autograft groups in comparison with the non-treated group (P<0.001). The immunohistochemistry (OC marker), biomechanical, and histomorphometric results indicated a significant improvement in the regeneration of the injured area in the groups treated with autologous bone and Zol-loaded scaffold compared to the non-treated group (P<0.05). CONCLUSION: The Zol-loaded scaffold accelerated bone regeneration, and led to enhanced structural performance and functional ability of the injured radial bone in rats.