Biomaterial-mediated blood clot formation: a key to unlocking osteogenic synergy for bone regeneration

Abstract Bone hemorrhage presents serious clinical challenges due to its high morbidity and mortality. Autologous coagulation forms blood clots that both halt bleeding and provide a natural scaffold for bone repair. The dynamic formation and dissolution of blood clots maintain a delicate balance between hemostasis and regeneration. Clot architecture and cytokine composition play pivotal roles in directing bone repair. These insights inspire biomimetic strategies using engineered biomaterials to regulate clot behavior, a central theme in designing bone-replacement systems that integrate hemostasis with osteogenesis. This review highlights the processes of clot formation following bone trauma and the contribution of cytokine-mediated signaling to bone repair. Particular emphasis is placed on how biomaterial implants modulate clot function via their physicochemical properties, such as chemical composition, structural characteristics, hydrophilicity, and surface charge. Additionally, the review examines the role of the clots during the early stages of bone injury and discusses the rational design principles for materials aimed at optimizing coagulation control and osteogenesis. Overall, this review reframes the clot not as a passive by-product of trauma but as an interface through which biomaterials seamlessly merge hemostasis and osteogenesis, offering a roadmap for multifunctional bone-replacement systems that halt bleeding while programming robust bone repair.