Cryogenic 3D printing of bifunctional silicate nanoclay incorporated scaffolds for promoted angiogenesis and bone regeneration

It remains challenging to manage critical-sized bone defects owing to insufficient vascularization. Tissue engineering scaffolds with favorable mechanical strength and excellent bone regenerative ability/angiogenic properties are recognized as promising platforms for bone defects. Various osteoinductive/angiogenic growth factors have been incorporated into scaffolds to enhance bone formation with the required vascularization. However, the instability and ease of inactivation of growth factors under certain physiological conditions limits their effectiveness. In the present study, a bifunctional laponite (LAP) with potent ability to induce both osteogenesis and angiogenesis was incorporated into poly(lactide-coglycolide)/β-tricalcium phosphate (PLGA/β-TCP) composite to form a porous scaffold through micro extrusion-based cryogenic three-dimensional printing. The hierarchically porous PLGA/β-TCP/LAP composite scaffold exhibited favorable initial mechanical strength and displayed a promoted effect towards cell adhesion of rat bone marrow derived mesenchymal stem cells and endothelial progenitor cells. Enhanced in vitro angiogenesis and osteogenesis were simultaneously achieved due to the proangiogenic and osteoinductive ions released from LAP. Furthermore, the PLGA/β-TCP/LAP scaffold promoted the generation of type H vessel and bony regeneration in vivo. Overall, the impartment of inorganic LAP into 3D printed PLGA/β-TCP scaffold provides a simple and efficient way to realize the treatment of critical-sized bone defects via improved angiogenesis and osteogenesis.