Pharmacological Targeting of Osteoimmunology and Immunometabolism in Bone Repair and Regeneration

Bone repair is a coordinated process involving inflammation, immune regulation, angiogenesis, osteogenesis, and tissue remodeling. Despite the intrinsic regenerative capacity of bone, impaired healing remains a major challenge in traumatic injury, metabolic disorders, aging, and inflammatory diseases. Emerging evidence indicates that dysregulation of the bone microenvironment, including altered immune responses, metabolic imbalance, and disrupted cellular communication, plays a critical role in regenerative outcomes. In particular, crosstalk between immune, osteogenic, and angiogenic cells, shaped by their metabolic state, is increasingly recognized as a key determinant of whether bone heals or fails, and offers new druggable targets. Yet current bone pharmacotherapy was developed mainly to treat systemic bone loss rather than to promote repair, and some widely used drugs, such as glucocorticoids, can impair healing. Regenerative pharmacology, the application of pharmacological sciences to accelerate, optimize, and characterize tissue regeneration, provides a framework to address this gap.This Research Topic aims to highlight recent advances in the pharmacological modulation of the immune and metabolic mechanisms that regulate bone repair. Particular emphasis will be placed on osteoimmunology and immunometabolic regulation as therapeutic targets: how drugs, endogenous mediators, and natural products act on immune responses, cellular metabolism, vascularization, and cell–cell interactions within the bone microenvironment to promote regeneration or reverse impaired healing. The pharmacological agent and its mechanism of action are the focus. We welcome studies on target validation, mechanism of action, and pharmacodynamic biomarkers, using complex in vitro and ex vivo systems, animal models of impaired healing, and early clinical studies. Drug delivery systems are within scope when they localize or control the action of a defined pharmacological agent. By integrating mechanistic and translational perspectives, this Research Topic aims to identify actionable targets and support new pharmacological strategies for fracture healing and bone defect repair.We welcome Original Research, Review, Mini Review, and Perspective articles addressing the pharmacological modulation of immune, metabolic, and microenvironmental mechanisms in bone repair and regeneration.Topics of interest include, but are not limited to:• Pharmacological modulation of osteoimmune crosstalk, including macrophage polarization, T-cell responses, and osteoclast–osteoblast coupling;• Drugs targeting immunometabolic pathways (e.g., glycolysis, AMPK/mTOR, HIF-1α) in osteogenic, angiogenic, and immune cells;• Small molecules, biologics, endogenous mediators, and natural products that enhance fracture healing or bone defect repair;• Drug repurposing and the effects of commonly used drugs on bone healing;• Mechanism of action, target validation, and pharmacodynamic biomarkers in complex in vitro, ex vivo, and in vivo models;• Drug delivery systems for localized, controlled release of immunomodulatory or metabolic agents;• Pharmacological strategies for impaired healing in aging, diabetes, osteoporosis, and chronic inflammation.Studies integrating mechanistic insights with translational potential are particularly encouraged. Manuscripts focused mainly on the design, fabrication, or physicochemical characterization of biomaterials, scaffolds, or tissue-engineered constructs, without a defined pharmacological agent and mechanism of action, are outside the scope. Computational or database-based studies (e.g., network pharmacology) without appropriate experimental validation are also outside the scope. Topic editors: Jinrong Lin, Changjiang Liu, YIFENG Yu, Dong Zhang Source: https://www.frontiersin.org/research-topics/86801/pharmacological-targeting-of-osteoimmunology-and-immunometabolism-in-bone-repair-and-regeneration