Abstract
Adult mammals are unable to regenerate bulky bone tissues, making large bone defects clinically challenging. Deer antler represents an exception to this rule, exhibiting the fastest bony growth in mammals, offering a unique opportunity to explore novel strategies for rapid bone regeneration. Here, a bone graft exploiting the biochemical, biophysical, and structural characteristics of antlers is constructed. It is decellularized antler cancellous bone (antler-DCB) to obtain a bone scaffold. Then, an antler-based bone graft is constructed by integrating antler-DCB with antler-derived biological signals, delivered by extracellular vesicles (EVs) from antler blastema progenitor cells (ABPCs), a novel stem cells responsible for antlerogenesis is discovered. The antler-based bone graft transformed bone marrow stromal cells into cells with an ABPC-like phenotype and transcriptomic signature. In vivo, the antler-based graft triggered rapid bone formation in a rat model, with doubled volume of newly formed bones than commercial DCBs. In addition, the antler-based graft orchestrated a coordinated process of vascularization, neurogenesis, and immunomodulation during osteogenesis, partially imitating early antlerogenesis. These findings provide practical insights to develop a therapeutic intervention for treating severe bone defects.