Direct 3D Printed Biomimetic Scaffolds Based on Hydrogel Microparticles for Cell Spheroid Growth

Abstract Biocompatible hydrogel inks with shear‐thinning, appropriate yield strength, and fast self‐healing are desired for 3D bioprinting. However, the lack of ideal 3D bioprinting inks with outstanding printability and high structural fidelity, as well as cell‐compatibility, has hindered the progress of extrusion‐based 3D bioprinting for tissue engineering. In this study, novel self‐healable pre‐cross‐linked hydrogel microparticles ( pc HμPs) of chitosan methacrylate (CHMA) and polyvinyl alcohol (PVA) hybrid hydrogels are developed and used as bioinks for extrusion‐based 3D printing of scaffolds with high fidelity and biocompatibility. The pc HμPs display excellent shear thinning when injected through a syringe and subsequently self‐heal into gels as shear forces are removed. Numerical simulations indicate that the pc HμPs experience a plug flow in the nozzle with minimal disturbance, which favors a steady and continuous printing. Moreover, the pc HμPs show a self‐supportive yield strength (540 Pa), which is critical for the fidelity of printed constructs. A series of biomimetic constructs with very high aspect ratio and delicate fine structures are directly printed by using the pc HμP ink. The 3D printed scaffolds support the growth of bone‐marrow‐derived mesenchymal stem cells and formation of cell spheroids, which are most important for tissue engineering.