The process of bone healing is a complex orchestration involving various bone cells such as osteoblasts, osteoclasts, and mesenchymal stem cells (MSCs), along with immune cells like macrophages. Essential cytokines such as transforming growth factor-β (TGF-β), bone morphogenetic protein-2 (BMP-2), and vascular endothelial-derived growth factor (VEGF) play pivotal roles in this intricate mechanism. Despite advancements in treating bone defects, the healing of significant bone injuries remains suboptimal, posing a critical challenge in clinical orthopedics. The bone healing process comprises three phases–inflammation, regeneration, and remodeling–each overlapping with the others. The early-stage, involving hematoma formation and immune cell activation, plays a crucial role in determining the subsequent bone healing process. Recent evidence suggests that biomaterials can influence hematoma and immune responses in bone healing, offering potential for improved osteoinductive and osteoconductive effects. This summary explores the impact of biomaterials on the initial-stage of bone healing, examining how their physiochemical properties can affect hematoma formation and interactions with immune cells. The findings propose strategies for bone tissue regeneration by targeting early-stage bone healing.