3D printed bioactive coated scaffolds boost osteogenesis and angiogenesis via the regulation of scaffold microstructure

Abstract Microstructure plays a crucial role in bone regeneration, conventional bone tissue engineering scaffold fabrication techniques often lack the precision required to control microstructural features that can optimize bone healing. 3D printing, as a powerful tool for biofabrication, allows for the design and optimization of scaffold microstructures to enhance bone healing. In this study, bioactive coated scaffolds composed of polycaprolactone (PCL) and tricalcium phosphate (TCP) were fabricated using a micro-extrusion 3D printer with varying compositions and microstructures, resulting in different physical and mechanical properties. Among these properties, porosity and permeability played a vital role in osteogenic and angiogenic differentiation. In vitro studies revealed that the permeability effect was dominant in osteogenic differentiation, while the porosity effect mainly induced the angiogenic differentiation, with potential mechanisms involving crosstalk between Wnt and PI3K signaling pathways. Moreover, significantly improved osteogenesis and angiogenesis were observed in U600 scaffolds compared to sham and U300 scaffolds, supporting the in vitro findings. This study provides valuable insights for the microstructure optimization of 3D printed tissue engineering scaffolds, which could facilitate the translation of 3D printing technology from the benchside to clinical applications.