Immunometabolism of macrophages in the bone microenvironment: a new perspective for bone healing therapy

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Immunometabolism, the regulation of immune cell function through metabolic pathways, has emerged as a key focus in regenerative medicine. Traditional bone healing therapies primarily target the osteoblast-osteoclast regulatory axis, overlooking the metabolic reprogramming of immune cells (e.g., macrophages) and limiting regenerative efficiency. Macrophages orchestrate bone healing through dynamic shifts between proinflammatory (M1-like) and reparative (M2-like) metabolic phenotypes. Recent studies have shown that their immunometabolic transitions govern the sequential phases of bone healing. Therefore, targeting macrophage immunometabolism may offer a novel therapeutic paradigm for bone regeneration. Aim of review This review summarizes recent advances in understanding how macrophage metabolism regulates bone healing, emphasizing the critical role of immunometabolism in resolving inflammation and regenerating tissue throughout the repair process. By integrating insights from the fields of cellular metabolism, microenvironmental signals, and biomaterial science, this review aims to offer an integrative perspective on how targeting macrophage metabolic control could serve as a therapeutic strategy to enhance bone regeneration. Key scientific concepts of review This review addresses five core concepts. First, it delineates the spatiotemporal roles and phenotypic shifts

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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