An ingenious design from nature to accelerate the repair of long-bone critical defects: the longitudinal tubular transverse interconnection structure of deer antlers.

Deer antlers, the only mammalian bony organs capable of complete regeneration, exhibit a growth rate of 2.7 cm/day, far surpassing human long bones (1 mm/day). Long-bone critical defects (LBCDs) occur when defects exceed intrinsic healing capacity. While antler stem cells drive regeneration, their immunogenicity limits clinical translation. Antler extracellular matrix (ECM) components have been proven to enhance bone repair, the role of its unique "longitudinal tubule-transverse connection" structure remains unexplored. Here, matrix scaffolds (devoid of cellular/active components) were prepared along longitudinal (L) or horizontal (H) axes, with cancellous scaffolds (R) as controls. Histological and in vitro analyses confirmed structural integrity and immunogenicity elimination. Bone marrow mesenchymal stem cells (BMSCs) exhibited structural guidance in morphology and migration on L. Ectopic implantation revealed no intrinsic osteogenic activity but demonstrated robust alignment of soft tissues along scaffold scaffolds. In rat femoral segmental defect models, L induced significantly greater depth and volume of oriented new bone (vs. H or R) while effectively blocking fibrous encapsulation. This study identifies antler-specific structural topology-rather than cellular or biochemical factors-as the critical osteoconductive driver enabling rapid bone regeneration. The findings establish a proof-of-concept for bioinspired structural designs in addressing LBCDs, providing guidance for the development of antler-derived bone replacement implants and biomimetic design of additive manufacturing implants.