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.

Abstract

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. An attempt was made to design a more efficient bone scaffold with polycaprolactone, polylactic acid, and hydroxyapatite. 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. 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.