Thermo‐Responsive Nanocomposite Bioink with Growth‐Factor Holding and its Application to Bone Regeneration

Three‐dimensional (3D) bioprinting, which is being increasingly used in tissue engineering, requires bioinks with tunable mechanical properties, biological activities, and mechanical strength for in vivo implantation. Herein, a growth‐factor‐holding poly(organophosphazene)‐based thermo‐responsive nanocomposite (TNC) bioink system is developed. The mechanical properties of the TNC bioink are easily controlled within a moderate temperature range (5–37 °C). During printing, the mechanical properties of the TNC bioink, which determine the 3D printing resolution, can be tuned by varying the temperature (15–30 °C). After printing, TNC bioink scaffolds exhibit maximum stiffness at 37 °C. Additionally, because of its shear‐thinning and self‐healing properties, TNC bioinks can be extruded smoothly, demonstrating good printing outcomes. TNC bioink loaded with bone morphogenetic protein‐2 (BMP‐2) and transforming growth factor‐beta1 (TGF‐β1), key growth factors for osteogenesis, is used to print a scaffold that can stimulate biological activity. A biological scaffold printed using TNC bioink loaded with both growth factors and implanted on a rat calvarial defect model reveals significantly improved bone regenerative effects. The TNC bioink system is a promising next‐generation bioink platform because its mechanical properties can be tuned easily for high‐resolution 3D bioprinting with long‐term stability and its growth‐factor holding capability has strong clinical applicability. A thermo‐responsive nanocomposite (TNC) bioink with thermally tunable mechanical properties, shear‐thinning behavior, and self‐healing ability is applied in 3D bioprinting without post‐printing chemical cross‐linking. Various biological activities can be bestowed on the TNC bioink by long‐term growth‐factor holding. On implantation, the growth‐factor‐loaded TNC bioink presents sustained biodegradation behavior with long‐term biological activities, giving way for newly formed tissue.