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Improved bone regeneration in rabbit bone defects using 3D printed composite scaffolds functionalized with osteoinductive factors.

Large critical size bone defects are complicated to treat and in many cases autografts become a challenge due to size and availability. In such situations, a synthetic bone implant that can be patient specifically designed and fabricated with control over parameters such as: porosity, rigidity and osteogenic cues, can act as a potential synthetic bone substitute. In this study we produced photocuring composite resins with poly(trimethylene carbonate) containing high ratios of bioactive ceramics and printed porous 3D composite scaffolds to be used as bone grafts. To enhance the overall surface area available for cell infiltration the scaffolds were also filled with a macroporous cryogel. Furthermore, the scaffolds were functionalized with osteoactive factors: bone morphogenetic protein (BMP) and zoledronic acid (ZA). The scaffolds were evaluated in vitro for biocompatibility and for functionality in vivo in critical bone defects (~8 mm) in two clinically relevant rabbit models. These studies included a smaller study in rabbit tibia and a larger study in the rabbit cranium. It was observed that the bioactive molecule functionalized 3D printed porous composite scaffolds provide an excellent conductive surface inducing higher bone formation and improved defect healing in both critical size long bone and cranial defects. Our findings provide strong evidence in favour of these composites as next generation synthetic bone substitutes.