Osteoinductive Agents-Incorporated Three-Dimensional Biphasic Polymer Scaffold for Synergistic Bone Regeneration

Large-scale bone defects are difficult to be regenerated entirely in the clinical practice. Bone tissue engineering has drawn more attention as an alternative to bone grafting owing to its convenience and flexibility. However, the low bioactivity of scaffolds and adverse effects of growth factors have hindered its practical application. Herein, the properties of poly(lactic-co-glycolic acid) (PLGA) scaffold, including hydrophilicity and mechanical strength, were improved by a gelatin coating incorporated with two small molecules, alendronate (ALD) and naringin (NG). Interestingly, these two drugs demonstrated a synergistic effect for the repair of rat calvarial defect, as ALD had an inhibitory impact on osteoclast activity and NG had an osteogenic effect on mesenchymal stem cells. From the results of histopathological staining and microcomputed tomography, the PLGA scaffold incorporated with gelatin, ALD, and NG (PLGA+Gelatin/ALD/NG) almost completely repaired the rat calvarial defect with physiological integrity at 16 weeks. In all, this biphasic scaffold can be a promising alternative to the conventional scaffold for clinical application.