Immediately implantable extracellular matrix-enriched osteoinductive hydrogel-laden 3D-printed scaffold for promoting vascularized bone regeneration in vivo

Reconstruction of patient-specific scaffolds to repair uniquely shaped bone defects remains a major clinical challenge in tissue engineering. Recently, three-dimensional (3D) printed scaffolds have received considerable attention as a promising technology for the rapid generation of custom shapes. However, synthetic polymers commonly used for 3D printing, such as polycaprolactone (PCL), lack the biological capacity to mimic native extracellular matrix functions to support cell growth and differentiation into desired tissues. We described the preparation and characterization of a 3D hybrid model for bone tissue engineering that comprises an extracellular matrix (ECM)-enriched hydrogel embedded in a PCL scaffold. The human bone marrow-derived mesenchymal stem cell–derived matrisome (BMTS) was utilized as a source of ECM-enriched biomacromolecules, and scaffold biocompatibility was evaluated in vitro using human bone marrow-derived mesenchymal stem cells (BM-MSCs). The 3D hybrid model exhibited excellent BM-MSC viability and osteogenic activity in vitro in both two-dimensional (2D) and 3D cultures. Furthermore, bone remodeling was evaluated by in vivo through a rat calvarial defect model; notably, the fabricated 3D hybrid model effectively enhanced vascularized bone regeneration. Therefore, this promising BMTS-based 3D hybrid model might serve as an excellent bone tissue-engineered scaffold for use in orthopedic applications.