The Biomaterial and Blood Clot Complex: A Crucial Early Environment for Osteo‐Coagulo‐Immunomodulation and the Advancement of Bone Biomaterials

Bone biomaterials have become essential medical materials in the standard clinical treatment of bone defects. The paradigm of bone biomaterials has shift progressed from bioinert, guidingosteoblasts‐guided, stem cells‐regulated, and osteoimmunomodulation. However, the osteogenic efficacy of bone biomaterials requires further enhancement, primarily due to the inherent challenges of precise osteoimmunomodulation. An important but overlooked event is blood clot formation, as the initial phase of tissue repair, and the inevitable interaction between blood and bone biomaterials. It results in the assembling of a biomaterial–blood clot complex (BBCC). This complex acts as a crucial starting point for subsequent osteoimmunomodulation. We firstly reviewed the paradigm shifts of bone biomaterials. The concept of “osteo‐coagulo‐immunomodulation” was further proposed which elucidates the spatiotemporal continuum of events comprising biomaterial coagulation and immune responses, emphasizing the role of key components of blood clots in osteoimmunomodulation (such as the fibrin network, red blood cells, platelets, and complement). Building on the “osteo‐coagulo‐immunomodulation” framework, strategies were inroduced to optimize the BBCC design by harnessing the unique properties of bone biomaterials and modulating the functions of blood clot components. This innovative concept aims to establish a new subdiscipline in the field of bone biomaterials research and stimulate further exploration into osteo‐coagulo‐immunomodulation.