Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives

Bone is increasingly recognized not as a passive structural scaffold but as a dynamic endocrine organ that secretes a diverse repertoire of bone-derived factors (BDFs) which establish communication axes with the brain, kidney, cardiovascular system, immune network and metabolic organs. Harnessing this endocrine potential for therapy requires technologies that interface with skeletal secretory programs with spatial, temporal and biological precision. Bioactive materials have emerged as a promising platform for this purpose. However, complete examples demonstrating that biomaterials regulate distant organ function through clearly defined BDF-dependent mechanisms remain limited; therefore, this Review discusses biomaterial-based intervention as an emerging framework built on current evidence from local skeletal repair, BDF-related marker regulation and controlled release studies. Concurrently, artificial intelligence may assist osteokine discovery, guiding biomaterial design and enabling patient-specific digital twins of bone-organ axis dynamics. This Review synthesizes current understanding of BDF-mediated inter-organ communication, critically evaluates biomaterial strategies and clinical lessons from BDF-related therapeutics, and proposes a framework for developing biomaterials at the interface of skeletal endocrine regulation and inter-organ communication, with attention to validation requirements, translational safety and off-target systemic effects.