Biologically Inspired Smart Release System Based on 3D Bioprinted Perfused Scaffold for Vascularized Tissue Regeneration

A critical challenge to the development of large-scale artificial tissue grafts for defect reconstruction is vascularization of the tissue construct. As an emerging tissue/organ manufacturing technique, 3D bioprinting offers great precision in controlling the internal architecture of a scaffold with preferable mechanical strength and printing complicated microstructures comparable to native tissue. However, current bioprinting techniques still exhibit difficulty in achieving biomimetic nano resolution and cooperating with bioactive spatiotemporal signals. In this study, a comprehensive design of engineered vascularized bone construct is presented for the first time by integrating biomimetic 3D bioprinted fluid perfused microstructure with biologically inspired smart release nanocoating, which is regarded as an aspiring concept combining engineering, biological, and material science. In this biologically inspired design, angiogenesis and osteogenesis are successively induced through a matrix metalloprotease 2 regulative mechanism by delivering dual growth factors with sequential release in spatiotemporal coordination. Availability of this system is evaluated in dynamic culture condition, which is similar to fluid surrounding in vivo, as an alternative animal model study. Results, particularly from co-cultured dynamically samples demonstrate excellent bioactivity and vascularized bone forming potential of nanocoating modified 3D bioprinted scaffolds for human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells.