Rat Calvarial Bone Regeneration by 3D-Printed Beta-Tricalcium Phosphate Incorporating MicroRNA-200c

Abstract

Advanced fabrication methods of bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid material approach that combined 3D-printed biodegradable, osteoconductive β-tricalcium phosphate (β-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed β-TCP scaffolds were fabricated utilizing suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of β-TCP. 3D-printed β-TCP scaffolds coated with miR-200c incorporated collagen increased the transfection efficiency of miR-200c and osteogenic differentiation of hBMSCs in vitro. Furthermore, these hybrid material, miR-incorporated scaffolds significantly enhanced bone regeneration in critical-sized rat calvarial defects. These results strongly indicate that through use of SEPS 3D-printing technology, hybrid scaffolds combined by osteoconductive biomaterials and osteoinductive biologics can be used as superior bone substitutes for the clinical treatment of large bone defects.