Personalized 3D‐Printed Scaffolds with Multiple Bioactivities for Bioroot Regeneration

Abstract Recent advances in 3D printing offer a prospective avenue for producing transplantable human tissues with complex geometries; however, the appropriate 3D‐printed scaffolds possessing the biological compatibility for tooth regeneration remain unidentified. This study proposes a personalized scaffold of multiple bioactivities, including induction of stem cell proliferation and differentiation, biomimetic mineralization, and angiogenesis. A brand‐new bioink system comprising a biocompatible and biodegradable polymer is developed and reinforced with extracellular matrix generated from dentin tissue (treated dentin matrix, TDM). Adding TDM optimizes physical properties including microstructure, hydrophilicity, and mechanical strength of the scaffolds. Proteomics analysis reveals that the released proteins of the 3D‐printed TDM scaffolds relate to multiple biological processes and interact closely with each other. Additionally, 3D‐printed TDM scaffolds establish a favorable microenvironment for cell attachment, proliferation, and differentiation in vitro. The 3D‐printed TDM scaffolds are proangiogenic and facilitate whole‐thickness vascularization of the graft in a subcutaneous model. Notably, the personalized TDM scaffold combined with dental follicle cells mimics the anatomy and physiology of the native tooth root three months after in situ transplantation in beagles. The remarkable in vitro and in vivo outcomes suggest that the 3D‐printed TDM scaffolds have multiple bioactivities and immense clinical potential for tooth‐loss therapy.