Harnessing Energy Metabolism for Enhanced Bone Defect Repair: Mechanisms and Therapeutic Strategies

Bone defect repair remains a significant challenge in clinical orthopedics, primarily due to the limitations of traditional techniques, such as insufficient osteogenic efficiency and non-functional bone regeneration. Recently, the regulation of energy metabolism has emerged as a promising avenue for bone regeneration. This review systematically examines the critical yet underexplored role of energy metabolism in bone regeneration, focusing on the dynamic regulatory mechanisms in osteoblasts and bone marrow mesenchymal stem cells across various metabolic pathways, and clarifies the influence of glucose metabolism and mitochondrial function on cellular proliferation and differentiation. Besides, three major repair strategies based on energy metabolism are summarized: enhancing cellular metabolic activity by combining cell derivatives; targeting the activation of metabolic pathways using active ions and enzymes; and modulating the local metabolic microenvironment through the topological structure and biochemical signals of biomimetic materials. Furthermore, deficiencies in current research—such as the lack of systematic analysis of metabolic networks, clinical validation, and multidisciplinary collaborative innovation—are noted. Future directions should explore the interplay between metabolism and epigenetics, the development of responsive metabolic regulatory materials, and advancements in clinical translation, ultimately advocating for a new paradigm in precise bone defect repair to significantly enhance patient outcomes.